Ionic liquid supported hydrogel-lipase biocatalytic systems in asymmetric synthesis of enantiomerically pure S-ibuprofen.

Novel hydrogel biocatalysts with immobilized lipase, stabilized by ionic liquids (ILs) of different hydrophobicity, were synthesized and evaluated. Variations of the time of immobilization and ratio of substrates during hydrogel synthesis were considered to obtain the most stable biocatalyst with the highest activity. Physicochemical characterization proved the success of the hydrogel synthesis and enzyme deposition on the surface of the support. Nevertheless, the key objective was to produce a biocatalyst for further application in ibuprofen methyl ester resolution, with the aim of obtaining an enantiomerically pure product. The hydrogel biocatalysts obtained in the presence of 5 wt% ILs after 8 h of immobilization achieved the highest activity recovery of 62 %. After 10 reaction cycles, enzymatic activity was still above 60 %, and the negative effect of pH and temperature on the activity of immobilized lipase was much lower than in the case of the free enzyme. After application of the catalyst in the resolution of ibuprofen methyl ester, the enantiomeric excess and conversion rate of the process were obtained for the dynamic kinetic resolution in isooctane. A conversion rate of 95 % was achieved due to the stabilization of the biocatalyst with IL and its resulting high catalytic activity. The study thus provides the pharmaceutical industry with a new potential approach with a strong scientific foundation.

Effect of Preemptive Analgesia on Pain Perception in Children: A Randomized Controlled Trial.

Background: Efforts have been made to minimize pain, prevent the development of needle fear, and promote positive experiences for children. The present study is designed to evaluate the effect of premedication with Ibugesic Plus before the administration of local anesthesia and extraction in children. Aim: The aim of the study is to assess the efficacy of preemptive analgesia on pain perception during local anesthesia administration and extraction in pediatric patients. Materials and methods: A total of 104 patients aged 7-10 years were selected who needed primary molar extraction. Group -Ibugesic Plus syrup was given 30 minutes prior to extraction. Group II-Placebo solution (B-Folcin syrup) was given 30 minutes prior to extraction. Pain level, pulse rate, and SpO2 were assessed using the Wong-Baker Faces Pain Rating Scale (WBFS) and pulse oximeter after injection, after extraction, and postoperatively. Results: The highest scores of pain were recorded after the time of injection and extraction. The patients who received preemptive analgesics (group I) reported significantly less pain than the placebo group (group II) at the time immediately after injection, after extraction, and 2 hours after extraction. Conclusion: The present study showed that preemptive analgesic administration may be considered a routine and rational pain management strategy in primary tooth extraction procedures in children. Clinical significance: Preemptive analgesia can be given to patients prior to dental procedures to reduce postoperative pain. How to cite this article: Virda M, Panda A, Kataria K. Effect of Preemptive Analgesia on Pain Perception in Children: A Randomized Controlled Trial. Int J Clin Pediatr Dent 2024;17(8):913-917.

Determination of Ibuprofen Enantiomers in Mouse Blood Using Liquid Chromatography-Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Study.

The aim of this study was to establish a simple, fast, and sensitive method with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneously determining ibuprofen enantiomers using mouse blood in very small volumes. LC-MS/MS equipped with an electrospray ionization (ESI) source was used in negative ion mode and multiple-reaction monitoring mode. Enantiomer chromatographic separation was carried out on a Lux® 5 µm Cellulose-3 (250 × 4.6 mm, 5 µm) column at a flow rate of 0.6 mL/min. Samples were pretreated by extracting only 5 µL of blood with 40 µL of acetonitrile (containing 1.3% formic acid) so that a concentration-time profile could be completed using a single mouse. 2-(4-Propylphenyl) propanoic acid was used as an internal standard. Standard curves for each enantiomer were linear from 0.04 to 80.00 µg/mL, demonstrating a lower limit of quantitation (LLOQ) than all previously reported methods. This method was completely validated and successfully executed to investigate the pharmacokinetics of ibuprofen enantiomers after intravenous administration of racemic ibuprofen, (S)-(+)-ibuprofen, and (R)-(-)-ibuprofen in Kunming mice, respectively. The results showed that the pharmacokinetic profiles of the (R)-(-)-ibuprofen and (S)-(+)-ibuprofen were significantly different, indicating the unidirectional inversion of R-(-)-ibuprofen to (S)-(+)-ibuprofen.

Antipyretic effect of oral dipyrone (Metamizole) compared to oral ibuprofen in febrile children: a systematic review and meta-analysis.

BACKGROUND: Dipyrone (Metamizole) is a potent pain reliever and fever reducer with muscle relaxant properties, most commonly used as an analgesic and antipyretic agent. Despite the fact that it has been banned in many high-income countries following confirmed studies of fatal agranulocytosis and adverse drug reactions, it is still widely used in various countries of the world. However, the antipyretic therapeutic indications of dipyrone in febrile children are currently unknown, and there is little information on the advantages and disadvantages of using dipyrone in febrile children. In febrile children, we expected that dipyrone's antipyretic effectiveness wouldn't be any more effective than ibuprofen. Therefore, the purpose of this research is to evaluate the effectiveness of oral dipyrone and oral ibuprofen as antipyretics in febrile children. METHODS: Several databases, including PubMed, Scopus, Web of Science, and Cochrane Library, were searched thoroughly using a pre-established search strategy for potential research. The studies included in this analysis comprised randomized controlled trials that compared the antipyretic effects of oral ibuprofen and oral dipyrone in febrile children. Data analysis was carried out using RevMan 5.4 software. RESULTS: Three studies were selected among the 27 publications we discovered to be applicable, and they underwent qualitative and quantitative analysis. The pooled analysis revealed no discernible difference between oral dipyrone and oral ibuprofen in terms of their antipyretic effects (Mean difference (MD) = 0.06; 95% confidence interval (CI): -0.08, 0.20). CONCLUSION: Both oral dipyrone and ibuprofen are effective in reducing high-temperature levels in febrile children without any significant difference.

An in vitro evaluation of intravenous lipid emulsion on three common canine toxicants.

Objective: To determine whether intravenous lipid emulsion (ILE) therapy significantly reduces the concentration of baclofen, ibuprofen, and/or bromethalin in canine whole blood over time. Animals: Seven 500 mL bags of canine DEA 1.1 negative blood were divided into aliquots of 125 mL and randomly assigned to one of three treatment groups (baclofen, ibuprofen, bromethalin) or four control groups (a positive control for each treatment group and a negative control group). Procedures: Injectable ibuprofen (200 mg/kg), baclofen (8 mg/kg), or bromethalin (3 mg/kg) was apportioned into 125 mL aliquots of canine whole blood and incubated for 30 min at 38.5°C. ILE (12.4 mL, Intralipid® ) was added to each sample and the solution vortexed [215 rpm for 15 min at 37°C (98.6°F)]. Samples were obtained at designated time points (0, 15, 30, 60, 180, 360 min), centrifuged, and separated into serum and RBC fractions. Serum samples were ultracentrifuged (22,000 g for 10 min at 37°C) to separate lipid rich and poor fractions. Samples were stored at -80°C prior to analysis. Results: A significant decrease in total drug concentration was established for bromethalin and its metabolite desmethylbromethalin compared to positive controls. ILE significantly reduced desmethylbromethalin at the 30-and 360-min time points. The remainder of the desmethylbromethalin time points did not reach significance. Bromethalin concentration was significantly reduced at all time points compared to positive controls. Neither baclofen nor ibuprofen had significant changes in concentration. Conclusion: ILE therapy was effective at reducing the total drug concentration of bromethalin and its metabolite desmethylbromethalin supporting the lipid sink theory. As a single compartment in vitro study, this study does not evaluate other proposed mechanisms of action of ILE therapy. ILE therapy may have other means of significantly decreasing lipophilic drug concentration in cases of toxicosis.

Exploring the hepatoprotective potential of the probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide-postbiotic on ibuprofen-induced acute liver injury in rats.

The present study investigates the hepatoprotective effect of a probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide (EPS) against ibuprofen-induced acute liver injury, and to explore the involved underlying mechanisms. Hepatotoxicity was induced by administration of a single dose of ibuprofen (200 mg/kg body weight). The Lpb. plantarum E1K2R2 (109 CFU) and its EPS (200 mg/kg bw) were separately used to feed rats for seven consecutive days before ibuprofen administration. Liver toxicity was assessed by monitoring levels of serum liver enzymes, liver relative weight, oxidative stress and inflammatory markers, and through histopathological analysis. The results showed that ibuprofen administration significantly increased (P < 0.05) liver relative weight, elevated levels of alanine-amino transferase (ALT), aspartate-amino transferase (AST), decreased hepatic gluthatione (GSH) and endogenous antioxidant enzymes including, superoxide dismutase (SOD), catalase (CAT) and increased malondialdehyde (MDA) levels, nitric oxide (NO) and myeloperoxidase (MPO) in hepatic tissues. However, pre-treatment with Lpb. plantarum E1K2R2 and its EPS significantly attenuated these toxicity manifestations. Both pre-treatments restored liver weight, normalized transaminase enzyme levels, enhanced the activity of liver antioxidant enzymes (SOD and CAT), increased GSH content, and significantly reduced NO, MPO and MDA levels (P < 0.05), indicating their protective role against oxidative stress and inflammatory response induced by ibuprofen. Furthermore, histopathological analysis confirmed regular liver morphology in rats pre-treated with the probiotic and its EPS. These findings highlight the potential effectiveness of the probiotic Lpb. plantarum E1K2R2 and its EPS in mitigating ibuprofen-induced liver toxicity.

Fabrication of ibuprofen/naringenin-coloaded into zein/sodium caseinate nanoparticles: evaluation of antiproliferative activity and apoptosis induction in liver cancer cells.

Nowadays, liver cancer is one of the most disturbing types of cancer that can affect either sex. Nanoparticles (NPs) of zein/sodium caseinate incorporating ibuprofen (IBU) and naringenin (NAR) have improved bioavailability and a high encapsulation efficiency (EE%). These nanoparticles are uniformly spherical. In vitro, cytotoxicity analysis on HepG2 cell lines, which are used to study human liver cancer, shows that encapsulated drugs (86.49% ± 1.90, and 78.52% ± 1.98 for NAR and IBU, respectively) have significantly lower IC50 values than individual drugs or their combined free form. In addition, the combination indices of 0.623 and 0.155 for IBU and NAR, respectively, show that the two have joint beneficial effects. The scratch wound healing assay results also show that the free drugs and the engineered NPs have a more significant anti-migratory effect than the untreated cells. The designed nanoparticles also reduce angiogenesis and proliferation while inducing apoptosis, according to in vitro results. In conclusion, a new approach to treating liver cancer may lie in the nanoencapsulation of numerous drugs within nanoparticles.

Combination of neuromuscular electrical stimulation and ibuprofen to reduce pain in femoral head necrosis.

OBJECTIVE: The combinative effects of neuromuscular electrical stimulation and ibuprofen on pain in patients with femoral head necrosis were discussed and analyzed. METHOD: This retrospective study analyzed data of 60 patients with femoral head necrosis hospitalized during Oct. 2020 to Oct. 2021. According to different treatment methods, the patients were divided into an observation group and a control group (30 cases in each group). The control group took oral ibuprofen sustained-release capsules, and the observation group was treated with neuromuscular electrical stimulation in addition to ibuprofen. Both groups received a 4-week treatment course. The therapeutic efficacy, Harris scale scores, Visual Analogue Scale (VAS) score, MRI hip imaging stage, SF-36 scale score, serum plasminogen activator inhibitor 1 (PAI-1), leptin and osteopontin levels before and after treatment were compared between the two groups. RESULTS: After treatment, the overall response rate in the observation group was higher than that in control group (P<0.05). The post-treatment scores of Harris scale were higher in both groups than those pre-treatment (P<0.05), and were higher in the observation group than in the control group (P<0.05). The VAS scores were decreased in both groups (P<0.05), and the decrease was more significant in the observation group than in the control group (P<0.05). After treatment, there were more patients with 0-I MRI hip imaging stage in the two groups than before treatment (P<0.05), and more in the observation group than in the control group (P<0.05). The SF-36 scores in both groups were increased (P<0.05), and the increase was more significant in the observation group than in the control group (P<0.05). The serum levels of PAI-1, leptin and osteopontin were decreased in both groups (P<0.05), and the decreases were more significant in the observation group than in the control group (P<0.05). CONCLUSION: The combinative treatment of neuromuscular electrical stimulation and ibuprofen has a significant effect on patients with femoral head necrosis. The treatment can remarkably reduce patients' pain, improve their hip function and quality of life, and decrease the PAI-1, leptin and osteopontin levels.

The Assessment of Knowledge, Attitude, and Practice of Paracetamol and Ibuprofen Administration Among Saudi Parents in the Makkah Region.

Introduction Paracetamol and ibuprofen, widely used for pediatric fever and pain, are safe when administered correctly. However, the caregiver's lack of understanding poses risks such as overdose. Addressing knowledge gaps is crucial due to reported variations in over-the-counter medication practices. "Fever phobia" underscores parental anxiety, stressing the ongoing need for research in this healthcare domain. Methodology This is a descriptive cross-sectional design targeting Saudi parents and caregivers from the Makkah region who have children aged 0-10 years. Data was collected via a self-administered validated online questionnaire in the Arabic language using a convenient sampling technique. The data was cleaned in Excel and analyzed using SPSS version 29 (IBM Inc., Armonk, New York). Results Our study included 449 parents and caregivers in the Makkah Region, of whom 337 (75.1%) were female, 179 (39.9%) were aged 18-29, and 425 (94.7%) were Saudi nationals. Knowledge assessment revealed gaps; e.g., only 86 (26.6%) identified baby weight as a dosage factor. Attitudes varied, with 152 (47.1%) associating paracetamol/ibuprofen with liver harm. Logistic regression showed no significant predictors for high-level knowledge, positive attitudes, or good practices, except for gender-influencing good practices (p=0.035, aOR=1.839). Significantly, males exhibited better practices regarding using of paracetamol. Conclusion Our study highlights knowledge gaps among parents and caregivers in the Makkah Region regarding pediatric fever management with paracetamol and ibuprofen. Attitudes varied, and gender significantly influenced good practices, with males demonstrating better adherence to the proper practice of managing children using paracetamol and ibuprofen.

Assessment of Blood Prostaglandin E2 Metabolite Levels among Infants Born Preterm with Patent Ductus Arteriosus: A Prospective Study.

OBJECTIVE: To assess the role of prostaglandin E2 by measuring blood prostaglandin E2 metabolite (PGEM) concentrations in preterm infants with patent ductus arteriosus (PDA). STUDY DESIGN: A prospective observational study of preterm infants born before 32 weeks of gestational age (GA) was performed in a single tertiary hospital in Japan. Blood samples were collected to measure serum concentrations of PGEM, ibuprofen (IBU), and cytokines. Multiple regression analyses assessed associations between blood PGEM levels and perinatal factors, development of hemodynamically significant PDA (hsPDA), and IBU treatment response of hsPDA. RESULTS: Seventy-nine infants (median GA 28 weeks) were enrolled in this study. Forty-seven received IBU for hsPDA treatment 1 d after birth in median. PDA closure occurred in 25 infants after a single IBU treatment. Serum PGEM concentrations were associated with histologic chorioamnionitis (P < .01), but not with GA, respiratory distress syndrome, or serum IL-6 concentrations. Serum PGEM concentrations decreased after initial IBU treatment; however, they were not associated with hsPDA development (P = .39). IBU concentrations correlated with IBU treatment response (aOR 1.29, P < .01). However, pre-IBU serum PGEM levels and PGEM reduction ratio did not (P = .13, .15, respectively). CONCLUSIONS: Serum PGEM concentrations in preterm infants were associated with maternal histologic chorioamnionitis, but not hsPDA development. IBU treatment response was associated with higher blood IBU concentrations, but not PGEM concentrations.

Pharmacological differences in postoperative cutaneous sensitivity, pain at rest, and movement-induced pain in laparotomized mice.

Postoperative pain management is challenging. We used mice with a transverse laparotomy to study tactile allodynia measured by the von Frey test, pain at rest measured by facial pain expressions detected by an artificial intelligence algorithm, and movement-induced pain measured by reductions in exploratory activity. The standard analgesics morphine and ibuprofen induced distinct patterns of outcome-dependent effects. Whereas morphine was more effective in reversing pain at rest compared to tactile allodynia, it was unable to alter movement-induced pain. Ibuprofen showed comparable effects across the three outcomes. Administered together, the compounds induced synergistic effects in the three aspects of postoperative pain, mirroring the known advantages of multimodal analgesia used in clinical practice. We explored the impact of neuroimmune interactions using a neutrophil depletion strategy. This reversed pain at rest and movement-induced pain, but did not alter cutaneous sensitivity. Non-peptidergic (IB4+) and peptidergic (CGRP+) nociceptors are segregated neuronal populations in the mouse. We tested the effects of gefapixant, an antitussive drug targeting non-peptidergic nociceptors through P2X3 antagonism, and olcegepant, an antimigraine drug acting as a CGRP antagonist. Both compounds reversed tactile allodynia, while only gefapixant reversed pain at rest, and none of them reversed movement-induced pain. In conclusion, tactile allodynia, pain at rest, and movement-induced pain after surgery have different pharmacological profiles, and none of the three aspects of postoperative pain can predict the effects of a given intervention on the other two. Combining these measures provides a more realistic view of postoperative pain and has the potential to benefit analgesic development.

Proven anti-virulence therapies in combating methicillin- and vancomycin-resistant Staphylococcus aureus infections.

Introduction: Despite years of efforts to develop new antibiotics for eradicating multidrug-resistant (MDR) and multi-virulent Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Staphylococcus aureus (VRSA) infections, treatment failures and poor prognoses in most cases have been common. Therefore, there is an urgent need for new therapeutic approaches targeting virulence arrays. Our aim is to discover new anti-virulence therapies targeting MRSA and VRSA virulence arrays. Methodology: We employed phenotypic, molecular docking, and genetic studies to screen for anti-virulence activities among selected promising compounds: Coumarin, Simvastatin, and Ibuprofen. Results: We found that nearly all detected MRSA and VRSA strains exhibited MDR and multi-virulent profiles. The molecular docking results aligned with the phenotypic and genetic assessments of virulence production. Biofilm and hemolysin productions were inhibited, and all virulence genes were downregulated upon treatment with sub-minimum inhibitory concentration (sub-MIC) of these promising compounds. Ibuprofen was the most active compound, exhibiting the highest inhibition and downregulation of virulence gene products. Moreover, in vivo and histopathological studies confirmed these results. Interestingly, we observed a significant decrease in wound area and improvements in re-epithelialization and tissue organization in the Ibuprofen and antimicrobial treated group compared with the group treated with antimicrobial alone. These findings support the idea that a combination of Ibuprofen and antimicrobial drugs may offer a promising new therapy for MRSA and VRSA infections. Conclusion: We hope that our findings can be implemented in clinical practice to assist physicians in making the most suitable treatment decisions.

Identification of a Novel Ibuprofen Biotransformation Pathway in Streptomyces sp. D218 and Detoxification as Indicated by the Green Algae Scenedesmus obliquus.

Ibuprofen, a widely used nonsteroidal anti-inflammatory drug, contaminates agricultural products and potentially threatens human health due to its frequent detection and poor biodegradability. Microbial metabolism dominates the elimination of residual ibuprofen in the environment. In mineral salt medium at pH 6 with 5 mM glucose, Streptomyces sp. D218 transformed ibuprofen concentrations ranging from 0.05 to 0.40 mM in 24 h. The optimal temperature, pH, and initial OD600 nm for ibuprofen transformation by strain D218 were 25-37 °C, 5.0-6.0, and 1.0-1.5, respectively. Strain D218 could simultaneously transform ibuprofen into the intermediates 2-hydroxyibuprofen and ibuprofen amide (IBUA). The two intermediates were further metabolized to 2-hydroxyibuprofen amide (2HIBUA), thus relieving the growth inhibition of ibuprofen in Scenedesmus obliquus. This is the first complete pathway reported for the detoxification of ibuprofen transformation by a Gram-positive strain. These findings further our understanding of the microbial catabolism of the IBU.

Comparative efficacy of pharmaceutical (Ibuprofen) and non-pharmaceutical (photobiomodulation, and chewing gum) interventions for pain reduction after elastomeric separator placement in orthodontic patients: a randomized clinical trial.

This study compared the efficacy of pharmaceutical (ibuprofen) and non-pharmaceutical (photobiomodulation and chewing gum) interventions for pain reduction after elastomeric separator placement in orthodontic patients. This 3-arm, parallel-group randomized clinical trial was conducted on 90 orthodontic patients. The level of anxiety and pain threshold of patients were measured at baseline using the Pain Catastrophizing Scale (PCS) and an algometer, respectively. The patients were randomly assigned to three groups (n = 30; equal number of males and females). In the laser group, 940 nm diode laser (Epic X, Biolase, USA, 12.35 J/cm2 energy density and 300 mW power in continuous-wave mode., The cross-sectional area of the laser handpiece tip was 1.7 cm2.) was irradiated to the buccal and lingual surfaces for 35 s each, prior to placement of separators. In the gum group, the patients were asked to chew a piece of sugar-free gum immediately after the placement of separators and repeat every 8 h for 5 min for one week in case of pain. In the ibuprofen group, patients received 400 mg ibuprofen (Hakim Pharmaceuticals, Tehran, Iran) after the placement of separators and were asked to take one tablet every 8 h for one week in case of pain. The pain score was recorded using the Modified McGill Pain Questionnaire (MPQ). The normality of data distribution was analyzed by the Kolmogorov-Smirnov test. ANOVA was applied to compare age, and the Chi-square and Monte Carlo Chi-square tests were used to compare gender and patient responses to the questions among the groups. Repeated measures ANOVA was used to compare the pain score at different time points and among the three groups. All statistical analyses were conducted using SPSS version 19 (SPSS Inc., Chicago, IL, USA) at 0.05 level of significance. Data analysis in this study had an intention to treat approach. Although the pain score was slightly lower in ibuprofen and gum groups, the difference among the three groups was not statistically significant (P > 0.05). 'Repeated measures ANOVA showed no significant effect of method of pain reduction on pain score (F = 1.520, P = 0.225). Time had a significant effect on pain score (F = 20.310, P < 0.001). The interaction effect of time and pain reduction method on pain score was not significant (F = 0.737, P = 0.651). patients experienced a lower level of pain in the ibuprofen and chewing gum groups, the difference in pain score was not significant among the three groups (P = 0.225). patients experienced a higher level of pain at 12 and 24 hours after the placement of separators in all groups. Considering the comparably equal analgesic efficacy of this modalities, non-pharmaceutical interventions can be used for pain reduction of elastomeric separator. The study protocol was registered in the Iranian Registry of Clinical Trials (IRCT20210927052611N1). Date of registration 2022/03/14.

Treatment outcomes and their predictors in children hospitalized with varicella complicated by bacterial superinfections after pandemic of COVID-19 - a retrospective multicenter analysis of real-life data in Poland.

PURPOSE: The aim of this study was to analyze treatment outcomes and their predictors in children hospitalized due to varicella complicated by bacterial superinfections after pandemic of COVID-19. METHODS: This retrospective study analyzed data collected in a multicenter, nationwide, observational database dedicated for children aged 0-17 years hospitalized due to bacterial complications of varicella in 9 Polish tertiary healthcare inpatient centers. The primary endpoint of this study was the treatment outcome established after the end of hospital management assessed at a 4-point scale. The secondary endpoint was defined as the necessity of surgical intervention. RESULTS: There were 458 patients with a median age of 4 (IQR 2-6) years. After the completed treatment, 319 (69%) participants were found fully recovered; 132 (29%) had transient complications; 2 (0.5%) had persistent complications; and 1 child (0.5%) died. Multivariate analysis revealed that implementation of ibuprofen in pre-treatment management of a child with varicella was associated with a 4.07-fold (2.50-6.60) increase in risk of complications after the treatment and it was associated with 2.87 times (1.39-5.89) higher risk of surgical intervention necessity. For other pre-hospital interventions (implementation of acyclovir, antibiotics or antihistaminics) no significant impact was observed. GAS infection increased the necessity of surgical intervention by 7.51 (3.64-15.49) times. CONCLUSIONS: One-third of patients treated for bacterial complications of varicella have post-treatment complications, most of them transient. GAS infection increases the need for surgical intervention. The use of ibuprofen in the treatment of varicella significantly increases the risk of complications and the need for surgical intervention.

Removal of ibuprofen, naproxen and 17-ß-estradiol in water using L. octovalvis constructed wetlands.

This study was developed to evaluate the removal potential of ibuprofen, naproxen and 17-ß-estradiol in artificial wetlands constructed on a laboratory scale, using eight experimental devices planted with L. octovalvis species, tested with gravel substrate and without gravel substrate, which were fortified with synthetic mixtures at concentrations of 1, 2 and 5 mg/L of the three compounds, during a batch exposure time of nine days. The removal efficiency for 17-ß-estradiol was 94.5 ± 2.47%, followed by ibuprofen 94.03 ± 1.96% and naproxen 81.57 ± 8.74%, respectively. The treatment with the highest removal was the one performed without the presence of gravel substrate. The highest removal efficiency occurred from the third day of exposure for the three compounds, so it was established as the optimum residence time. The model that best explained the adsorption process of the three compounds studied, was the Langmuir isotherm. The observed results demonstrate that L. octovalvis can be used as a native species in artificial wetlands for the efficient removal of pharmaceutical compounds.

Through the use of a macrophyte plant native to the state of Morelos, an artificial wetland was built, which was capable of removing several drugs with tolerance to changes in concentration, which constitutes an economic and sustainable alternative that can be coupled to the treatment of wastewater contaminated with this type of compounds.

Ibuprofen: The Hidden Culprit Behind Aseptic Meningitis.

Drug-induced aseptic meningitis represents a significant clinical entity characterized by an inflammatory response of the meninges triggered by specific pharmacological agents. This condition predominantly manifests as a delayed hypersensitivity reaction to a variety of drugs, most notably non-steroidal anti-inflammatory drugs, antibiotics, immune checkpoint inhibitors, and monoclonal antibodies. We report a case of aseptic meningitis in a 54-year-old male presenting with nausea and blurred vision two hours after taking ibuprofen. This case aims to highlight one underrecognized adverse event associated with one of the most commonly used over-the-counter medications worldwide.

Exploring the Causal Relationship between Ibuprofen Use and Osteoarthritis Risk: A Mendelian Randomization Study.

This study explored the potential causal relationship between ibuprofen (IBU) use and the risk of developing osteoarthritis, a prevalent joint disorder characterized by pain and stiffness. We conducted a two-sample MR analysis using four distinct OA GWAS datasets as outcomes and single-nucleotide polymorphisms (SNPs) associated with IBU metabolism as exposures. The inverse variance weighted (IVW) and weighted median methods were utilized to assess the causal association by meta-analysis, while pleiotropy and heterogeneity were evaluated using MR-Egger regression and Cochran's Q statistics. The MR analysis provided strong evidence for a causal association between IBU use and an increased risk of OA. A meta-analysis of the IVW and weighted median results across all datasets demonstrated an OR = 1.116 (95% CI = 1.063-1.170) and an OR = 1.110 (95% CI = 1.041-1.184). The consistency of the results obtained from different methods enhanced the reliability of the findings. Low pleiotropy and minimal heterogeneity were observed, further validating the results. The study supports a causal link between IBU use and an increased risk of OA, suggesting that IBU may accelerate the progression of OA while relieving symptoms. These findings highlight the importance of cautious use of IBU in clinical practice, especially considering its potential impact on long-term joint health.

Aspirin may be more suitable for patients with major depression: Evidence from two-sample Mendelian randomization analysis.

OBJECTIVE: Utilizing two-sample Mendelian randomization (TSMR) analysis, this study aims to explore the potential bidirectional causal relationship between common nonsteroidal anti-inflammatory drugs (paracetamol, ibuprofen, aspirin) and major depression (MD) from a genetic standpoint. METHODS: We employed summarized data from a Genome-Wide Association Study (GWAS) of European populations. The inverse variance weighted (IVW) method was used for TSMR analysis; outcomes were evaluated based on p-value, OR (Odds Ratio), and 95% confidence interval (95% CI). RESULTS: From a genetic perspective, the study found that the use of paracetamol and ibuprofen increased the risk of MD (IVW (MRE): OR = 2.314, 95% CI: 1.609-3.327; p = 6.07E-06) and (IVW (MRE): OR = 2.308, 95% CI: 1.780-3.653; p = 0.002), respectively. No significant causal relationship was found between aspirin and MD (p > 0.05). Reverse TSMR analysis found that MD increased the genetic predisposition to use paracetamol, ibuprofen, and aspirin (IVW (MRE): OR = 1.042, 95% CI: 1.030-1.054, p = 3.07E-12), (IVW (FE): OR = 1.015, 95% CI: 1.007-1.023, p = 1.13E-04), (IVW (MRE): OR = 1.019, 95% CI: 1.009-1.030, p = 4.22E-04), respectively. Other analytical methods and sensitivity analyses further supported the robustness and reliability of these findings. CONCLUSION: This study provides preliminary genetic evidence through bidirectional TSMR analysis that MD increases the genetic predisposition to use paracetamol, ibuprofen, and aspirin, aiding clinicians in devising preventive strategies against the misuse of non-steroidal anti-inflammatory drugs. Moreover, we found that the use of paracetamol and ibuprofen increases the risk of MD, whereas aspirin did not. This suggests a crucial clinical implication: clinicians treating MD patients could opt for the relatively safer aspirin over paracetamol and ibuprofen.

Ibuprofen­derived nitric oxide donors with a high affinity to human serum albumin induce cell death in pancreatic cancer cells through a non­caspase 3/7­mediated pathway.

Nitric oxide (NO) has been reported to have a cytotoxic effect on various types of cancer. However, the efficient delivery of NO donors to tumors remains challenging. The present study used ibuprofen, which has a high binding affinity to human serum albumin (HSA). A total of two types of nitrated forms of ibuprofen, 4-[(nitrooxy)methyl]benzyl 2-(4-isobutylphenyl)propanoate [nitrated ibuprofen benzyl linker (NIB)] and 2-(nitrooxy)ethyl 2-(4-isobutylphenyl) propanoate [nitrated ibuprofen ethyl linker (NIE)], were synthesized. It was demonstrated that both NIB and NIE bound to the ibuprofen-binding site of HSA. Although NOx release was observed from NIB, but not NIE, intracellular NO release was detected from both NIB and NIE, which indicated that the mechanisms of NO release may be different for NIB and NIE. Both NIB and NIE induced concentration- and time-dependent cell death in human pancreatic cancer cells, whereas this cell death was not observed with ibuprofen, which could suggest that these cell death-inducing effects may be mediated by NO. The non-specific caspase inhibitor, z-VAD-FMK, inhibited cell death induced by NIB and NIE, but activation of caspase 3/7 was not observed. These results suggested that both NIB and NIE induced cell death through a non-caspase 3/7 pathway. The findings of the present study demonstrated that both NIB and NIE, as NO donors that could be retained in blood, may potentially be useful anti-cancer agent candidates in the future.