Ibuprofen-induced multiorgan malformation during embryogenesis in Xenopus laevis (FETAX).

Ibuprofen, one of the most commonly prescribed nonsteroidal anti-inflammatory drugs, has not been fully assessed for embryonic toxicity in vertebrates. Here, we systematically assessed the embryotoxicity of ibuprofen in Xenopus laevis at various concentrations during embryogenesis. Embryos were treated with different concentrations of ibuprofen, ranging from 8 to 64 mg/L, at 23 °C for 96 h, and examined daily and evaluated at 72 hpf. Lethal or teratogenic effects were documented. For histological analysis, paraffin embedded embryos were transversely sectioned at a thickness of 10-µm and stained with hematoxylin and eosin. Total RNA was isolated from embryos at stages 6, 12, 22 and 36, and real-time quantitative PCR was performed. Ibuprofen-treated embryos showed delayed or failed dorsal lip formation and its closure at the beginning of gastrulation. This resulted in herniation of the endodermal mass after gastrulation under high concentrations of ibuprofen-treated embryos. Underdeveloped intestines with stage and/or intestinal malrotation, distorted microcephaly, and hypoplastic heart, lungs, and pronephric tubules were observed in ibuprofen-treated embryos. Cephalic, cardiac, and truncal edema were also observed in them. The severity of the deformities was observed in a concentration-dependent manner. The teratogenic index was 2.28. These gross and histological disruptions correlated well with the altered expression of each organ marker gene. In conclusion, ibuprofen induced delayed and disrupted gastrulation in the early developmental stage and multiorgan malformation later in the organogenesis stage of Xenopus laevis embryos.

Thermal effects and drugs competition on the palmitate binding capacity of human serum albumin.

Human serum albumin (HSA) is the most abundant plasma protein of the circulatory system. It is a multidomain, multifunctional protein that, combining diverse affinities and wide specificity, binds, stores, and transports a variety of biological compounds, pharmacores, and fatty acids. HSA is finding increasing uses in drug-delivery due to its ability to carry functionalized ligands and prodrugs. All this raises the question of competition for binding sites occupancy in case of multiple ligands, which in turn influences the protein structure/dynamic/function relationship and also has an impact on the biomedical applications. In this work, the effects of interactive binding of palmitic acid (PA), warfarin (War) and ibuprofen (Ibu) on the thermal stability of HSA were studied using DSC, ATR-FTIR, and EPR. PA is a high-affinity physiological ligand, while the two drugs are widely used for their anticoagulant (War) and anti-inflammatory (Ibu) efficacy, and are exogenous compounds that accommodate in the deputed drug site DS1 and DS2, respectively overlapping with some of the fatty acid binding sites. The results indicate that HSA acquires the highest thermal stability when it is fully saturated with PA. The binding of this physiological ligand does not hamper the binding of War or Ibu to the native state of the protein. In addition, the three ligands bind simultaneously, suggesting a synergic cooperative influence due to allosteric effects. The increased thermal stability subsequent to binary and multiple ligands binding moderates protein aggregation propensity and restricts protein dynamics. The biophysics findings provide interesting features about protein stability, aggregation, and dynamics in interaction with multiple ligands and are relevant in drug-delivery.

Synthesis, molecular dynamics simulation, and evaluation of biological activity of novel flurbiprofen and ibuprofen-like compounds.

The frequent use of anti-inflammatory drugs and the side effects of existing drugs keep the need for new compounds constant. For this purpose, flurbiprofen and ibuprofen-like compounds, which are frequently used anti-inflammatory compounds in this study, were synthesized and their structures were elucidated. Like ibuprofen and flurbiprofen, the compounds contain a residue of phenylacetic acid. On the other hand, it contains a secondary amine residue. Thus, it is planned to reduce the acidity, which is the biggest side effect of NSAI drugs, even a little bit. The estimated ADME parameters of the compounds were evaluated. Apart from internal use, local use of anti-inflammatory compounds is also very important. For this reason, the skin permeability values of the compounds were also calculated. And it has been found to be compatible with reference drugs. The COX enzyme inhibitory effects of the obtained compounds were tested by in vitro experiments. Compound 2a showed significant activity against COX-1 enzyme with an IC50 = 0.123 + 0.005 µM. The interaction of the compound with the enzyme active site was clarified by molecular dynamics studies.

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.

Fast and efficient extraction and determination of nonsteroidal anti-inflammatory drugs using poly(8-hydroxyquinoline)-coated magnetic graphene oxide nanocomposite prior to capillary electrophoresis analysis in wastewater, breast milk, and urine samples.

In this study, magnetic graphene oxide coated with poly(8-hydroxyquinoline) was successfully synthesized, characterized, and utilized as a novel sorbent for the ultrasonic-assisted dispersive magnetic solid-phase extraction of naproxen and ibuprofen. These analytes served as representative analytes for two nonsteroidal anti-inflammatory drugs in various real samples. Characterization techniques, such as IR, X-ray powder diffraction, field emission scanning electron microscopy, energy-dispersive X-ray-mapping, and Brunauer-Emmett-Teller (BET), were used to confirm the correctness synthesis and preparation of the nanocomposites. Effective parameters on the extraction efficiency were investigated to maximize the analytical performance of the developed method. The dynamic range (1-1000 µg L-1), coefficients of determination (R2 ≥ 0.997), the limits of detection (0.3-1.0 µg L-1), and limit of quantification (1.0-3.0 µg L-1), intra-day and inter-day precisions (3.5%-7.2%) were achieved. The method validation results showed extraction recovery ranging from 80.4% to 96.0% and preconcentration factors ranging from 137 to 140.

Mechanistic insights on the antibacterial action of the kyotorphin peptide derivatives revealed by in vitro studies and Galleria mellonella proteomic analysis.

OBJECTIVES: The selected kyotorphin derivatives were tested to improve their antimicrobial and antibiofilm activity. The antimicrobial screening of the KTP derivatives were ascertained in the representative strains of bacteria, including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli and Pseudomonas aeruginosa. METHODS: Kyotorphin derivatives, KTP-NH2, KTP-NH2-DL, IbKTP, IbKTP-NH2, MetKTP-DL, MetKTP-LD, were designed and synthesized to improve lipophilicity and resistance to enzymatic degradation. Peptides were synthesized by standard solution or solid-phase peptide synthesis and purified using RP-HPLC, which resulted in >95 % purity, and were fully characterized by mass spectrometry and 1H NMR. The minimum inhibitory concentrations (MIC) determined for bacterial strains were between 20 and 419 µM. The direct effect of IbKTP-NH2 on bacterial cells was imaged using scanning electron microscopy. The absence of toxicity, high survival after infection and an increase in the hemocytes count was evaluated by injections of derivatives in Galleria mellonella larvae. Proteomics analyses of G. mellonella hemolymph were performed to investigate the underlying mechanism of antibacterial activity of IbKTP-NH2 at MIC. RESULTS: IbKTP-NH2 induces morphological changes in bacterial cell, many differentially expressed proteins involved in DNA replication, synthesis of cell wall, and virulence were up-regulated after the treatment of G. mellonella with IbKTP-NH2. CONCLUSION: We suggest that this derivative, in addition to its physical activity on the bacterial membranes, can elicit a cellular and humoral immune response, therefore, it could be considered for biomedical applications.

Ibuprofen and Other Arylpropionics: The Relevance in Immediate Hypersensitivity Drug Reactions.

BACKGROUND: Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is the most frequent medication to be involved in hypersensitivity drug reactions (HDRs). Other analgesic/anti-inflammatory drugs in the arylpropionic group are also relevant, albeit to a lesser extent. Ibuprofen is widely consumed by people of all ages, both on medical prescription and over the counter; moreover, it is an organic contaminant of surface waters and foods. While numerous drugs cause HDR, ibuprofen's underlying mechanisms are more intricate and involve both specific immunological and non-immunological mediated reactions. SUMMARY: we concentrate on immediate responses, including urticaria with or without angioedema, anaphylaxis, and angioedema, classifying reactions according to whether they are caused by single or multiple NSAIDs and based on the mechanisms at play. Both groups may experience anaphylaxis, defined as an immediate, severe systemic reaction involving at least two organs, though the frequency and severity can vary. Following this classification, more clinical manifestations can be identified. Diagnosis is partly based on a detailed clinical history, including information about ibuprofen and/or other arylpropionic derivatives involved, the interval between drug intake and symptoms onset, clinical manifestations, number of episodes, and the patient's tolerance or response to other medications - mainly non-chemically related NSAID - both before and after reactions to ibuprofen and/or other arylpropionic drugs. A drug provocation test is frequently necessary to make a diagnosis. KEY MESSAGE: Because ibuprofen is the most widely prescribed NSAID, it is reasonable to assume its role as the leading cause of HDR will only become more important.

Biotransformation activities of fungal strain apiotrichum sp. IB-1 to ibuprofen and naproxen.

Ibuprofen (IBU) and naproxen (NPX), as widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs), are largely produced and consumed globally, leading to frequent and ubiquitous detection in various aqueous environments. Previously, the microbial transformation of them has been given a little attention, especially with the isolated fungus. A yeast-like Apiotrichum sp. IB-1 has been isolated and identified, which could simultaneously transform IBU (5 mg/L) and NPX (2.5 mg/L) with maximum efficiencies of 95.77% and 88.31%, respectively. For mono-substrate, the transformation efficiency of IB-1 was comparable to that of co-removal conditions, higher than most of isolates so far. IBU was oxidized mainly through hydroxylation (m/z of 221, 253) and NPX was detoxified mainly via demethylation (m/z of 215) as shown by UPLC-MS/MS results. Based on transcriptome analysis, the addition of IBU stimulated the basic metabolism like TCA cycle. The transporters and respiration related genes were also up-regulated accompanied with higher expression of several dehydrogenase, carboxylesterase, dioxygenase and oxidoreductase encoding genes, which may be involved in the transformation of IBU. The main functional genes responsible for IBU and NPX transformation for IB-1 should be similar in view of previous studies, which needs further confirmation. This fungus would be useful for potential bioremediation of NSAIDs pollution and accelerate the discovery of functional oxidative genes and enzymes different from those of bacteria.

Ibuprofen delays ovulation by several hours: prospective controlled study in natural cycles with HCG-triggered ovulation.

RESEARCH QUESTION: Does ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), delay ovulation? DESIGN: Two-stage, proof-of-concept, controlled study, assessing the percentage of non-ovulated follicles 42 h after HCG injection in patients taking ibuprofen. The intervention group consisted of women undergoing natural cycle IVF treatment taking ibuprofen 3 × 400 mg per day. The control group consisted of women undergoing timed sexual intercourse or intrauterine insemination. The proportion of patients with non-ovulated follicles in the ibuprofen group was first compared against a reference of 50% using a one-sample binomial test, and second against the proportion observed in the control group using an adjusted logistic regression. RESULTS: A total of 26 women were recruited in the ibuprofen intervention group. Twenty-five patients were recruited in the control group. The proportion of patients with delayed ovulation observed (22/26 [84.6%]; 95% CI 65.1% to 95.6%) was significantly higher than the reference of 50% (P < 0.001). In the control group, the proportion of patients with delayed ovulation was 20.0% ([5/25], 95% CI 6.8% to 40.7%). Compared with the ibuprofen group, a significantly increased probability of a delayed ovulation was found in the ibuprofen intervention group (adjusted OR 22.72, 95% CI 5.77 to 115; P < 0.001). Of the 22 women with delayed ovulation, oocytes were retrieved in 20 women (90.9%) and all oocytes were mature (metaphase II). CONCLUSIONS: Women trying to conceive should avoid non-selective NSAIDs around the time of ovulation. Ibuprofen or other NSAID can be used to delay ovulation for several hours in assisted reproductive technology and other infertility treatments if required.

Drug-induced liver injury (DILI) ascribed to non-steroidal anti-inflammatory drugs (NSAIDs) in the USA-Update with genetic correlations.

OBJECTIVE: To describe patients with NSAID-DILI, including genetic factors associated with idiosyncratic DILI. METHODS: In DILIN, subjects with presumed DILI are enrolled and followed for at least 6 months. Causality is adjudicated by a Delphic approach. HLA sequencing of multiethnic NSAID-DILI patients and HLA allele imputation of matching population controls were performed following overall, class and drug-based association analysis. Significant results were tested in a non-Hispanic White (NHW) case-control replication cohort. RESULTS: Between September 2004 and March 2022, causality was adjudicated in 2498, and 55 (41 [75%] women) were assessed as likely due to NSAIDs. Median age at onset was 55 y (range 22-83 y). Diclofenac was the causative drug in 29, celecoxib in 7, ibuprofen in 5, etodolac and meloxicam each in 4. Except for meloxicam and oxaprozin (n = 2), the liver injury was hepatocellular with median R 15-25. HLA-DRB1*04:03 and HLA-B*35:03 were significantly more frequent in NSAID-DILI patients than in non-NSAID DILI controls. Interestingly, 85% of the HLA-DRB1*04:03 carriers developed DILI due to the use of acetic acid derivative NSAIDs, supporting the hypothesis that HLA-DRB1*04:03 could be a drug and/or class risk factor. HLA-B*35:03 but not HLA-DRB1*04:03 association was confirmed in the independent NHW replication cohort, which was largely driven by diclofenac. CONCLUSIONS: Despite prevalent use, NSAID-DILI is infrequent in the United States. Diclofenac is the most commonly implicated, and adherence to warnings of risk and close observation are recommended. The increased frequency of HLA-B*35:03 and DRB1*04:03, driven by diclofenac, suggests the importance of immune-mediated responses.

Fluorinated PAMAM-Arginine Carrier Prodrugs for pH-Sensitive Sustained Ibuprofen Delivery.

OBJECTIVE: The development of an efficient, multifunctional drug delivery system overcoming different obstacles generally associated with drug formulations, including the poor accumulation of the active principle in the target site and its sustained release for prolonged time. METHODS: Our study proposes the development of a fluorinated poly(amidoamine) (PAMAM) carrier prodrug combining drug release boosted in alkaline environments with a possible implementation in 19F MRI applications. In particular, we functionalized the terminal primary amines of PAMAM G2 and G4 through an ad hoc designed fluorinated ibuprofen-arginine Michael acceptor to obtain multifunctional ibuprofen-PAMAM-Arg conjugates. RESULTS: These carriers demonstrated pH-dependent and sustained ibuprofen release for more than 5 days. This advantage was observed in both weak alkaline and physiological buffer solutions, allowing to overcome the limits associated to the burst release from similar fluorinated Arg-PAMAM dendrimers with ibuprofen physically encapsulated. CONCLUSION: These findings, coupled to the high biocompatibility of the system, suggest a potential synergistic biomedical application of our conjugates, serving as vehicles for drug delivery and as 19F magnetic resonance imaging contrast agents.

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.

Solubility vs Dissolution in Physiological Bicarbonate Buffer.

BACKGROUND: Phosphate buffer is often used as a replacement for the physiological bicarbonate buffer in pharmaceutical dissolution testing, although there are some discrepancies in their properties making it complicated to extrapolate dissolution results in phosphate to the in vivo situation. This study aims to characterize these discrepancies regarding solubility and dissolution behavior of ionizable compounds. METHODS: The dissolution of an ibuprofen powder with a known particle size distribution was simulated in silico and verified experimentally in vitro at two different doses and in two different buffers (5 mM pH 6.8 bicarbonate and phosphate). RESULTS: The results showed that there is a solubility vs. dissolution mismatch in the two buffers. This was accurately predicted by the in-house simulations based on the reversible non-equilibrium (RNE) and the Mooney models. CONCLUSIONS: The results can be explained by the existence of a relatively large gap between the initial surface pH of the drug and the bulk pH at saturation in bicarbonate but not in phosphate, which is caused by not all the interfacial reactions reaching equilibrium in bicarbonate prior to bulk saturation. This means that slurry pH measurements, while providing surface pH estimates for buffers like phosphate, are poor indicators of surface pH in the intestinal bicarbonate buffer. In addition, it showcases the importance of accounting for the H2CO3-CO2 interconversion kinetics to achieve good predictions of intestinal drug dissolution.

Automated Image-Based Fluorescence Screening of Mitochondrial Membrane Potential in Daphnia magna: An Advanced Ecotoxicological Testing Tool.

This study demonstrated the strengths of in vivo molecular staining coupled with automated imaging analysis in Daphnia magna. A multiwell plate protocol was developed to assess mitochondrial membrane potential using the JC-1 dye. The suitability of five common anesthetics was initially tested, and 5% ethanol performed best in terms of anesthetic effects and healthy recovery. The staining conditions were optimized to 30 min staining with 2 µM JC-1 for best J-aggregate formation. The protocol was validated with the model compound carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and used to measure the effect of four environmental contaminants, 2,4-dinitrophenol, triclosan, n-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), and ibuprofen, on mitochondrial health. Test organisms were imaged using an automated confocal microscope, and fluorescence intensities were automatically quantified. The effect concentrations for CCCP were lower by a factor of 30 compared with the traditional OECD 202 acute toxicity test. Mitochondrial effects were also detected at lower concentrations for all tested environmental contaminants compared to the OCED 202 test. For 2,4-dinitrophenol, mitochondria effects were detectable after 2 h exposure to environmentally relevant concentrations and predicted organism death was observed after 24 h. The high sensitivity and time efficiency of this novel automated imaging method make it a valuable tool for advancing ecotoxicological testing.

Fenamates and ibuprofen as foundational components in the synthesis of innovative, targeted COX-2 anti-inflammatory drugs, undergoing thorough biopharmacological assessments and in-silico computational studies.

Cyclooxygenase-2 plays a vital role in inflammation by catalyzing arachidonic acid conversion toward prostaglandins, making it a prime therapeutic objective. Selective COX-2 inhibitors represent significant progress in anti-inflammatory therapy, offering improved efficacy and fewer side effects. This study describes the synthesis of novel anti-inflammatory compounds from established pharmaceutically marketed agents like fenamates III-V and ibuprofen VI. Through rigorous in vitro testing, compounds 7b-c, and 12a-b demonstrated substantial in vitro selective inhibition, with IC50 values of 0.07 to 0.09 µM, indicating potent pharmacological activity. In vivo assessment, particularly focusing on compound 7c, revealed significant anti-inflammatory effects. Markedly, it demonstrated the highest inhibition of paw thickness (58.62 %) at the 5-hr mark compared to the carrageenan group, indicating its potency in mitigating inflammation. Furthermore, it exhibited a rapid onset of action, with a 54.88 % inhibition observed at the 1-hr mark. Subsequent comprehensive evaluations encompassing analgesic efficacy, histological characteristics, and toxicological properties indicated that compound 7c did not induce gastric ulcers, in contrast to the ulcerogenic tendency associated with mefenamic acid. Moreover, compound 7c underwent additional investigations through in silico methodologies such as molecular modelling, field alignment, and density functional theory. These analyses underscored the therapeutic potential and safety profile of this novel compound, warranting further exploration and development in the realm of pharmaceutical research.

Pharmacovigilance of nephrotoxic drugs in neonates: the Pottel method for acute kidney injury detection in ELBW neonates.

BACKGROUND: Extremely low birth weight (ELBW) neonates (birth weight ≤ 1000 g) are at high risk to develop drug-induced acute kidney injury (AKI). However, we lack a pragmatic detection tool to capture their time-dependent (patho)physiologic serum creatinine (Scr) patterns. Pottel et al. suggested rescaling Scr by dividing Scr with the mean Scr value of the age- and sex-specific reference population. We explored if this Pottel method can detect drug-related nephrotoxicity in ELBW neonates. METHODS: A previously reported dataset on Scr changes in ELBW neonates exposed to ibuprofen, amikacin, or vancomycin was updated to calculate Pottel scores for every available Scr value in the first 28 postnatal days. We hereby used previously published postnatal age-specific 50th centile values in an ELBW population. Linear mixed models were applied, analyzing Pottel scores as response variable and continuous time (day), drug exposure, and interaction thereof in the explanatory model. RESULTS: Serum creatinine (n = 3231) observations in 201 ELBW neonates were collected. A statistically significant rise of Pottel scores was observed with ibuprofen starting from postnatal day 4. In addition, a cumulative effect of treatment with mean Pottel scores on day 0 of 1.020 and on day 3 during treatment of 1.106 (95% CI 1.068-1.145, p < 0.001) was observed, corrected for effect of antibiotics. Antibiotic administrations showed a small but statistically significant difference up to postnatal day 5. CONCLUSIONS: As rescaled Scr biomarker, the Pottel method showed a clear association with ibuprofen-exposed ELBW neonates, suggesting its applicability as a pragmatic bedside alternative tool to assess nephrotoxicity.

Efficiently photocatalysis activation of peroxymonosulfate by bimetallic metal-organic frameworks Mn-MIL-53(Fe) for ibuprofen degradation: Synergistic efficiency, mechanism and degradation pathways.

In this study, a UV-driven photocatalytic activation of peroxymonosulfate (PMS) system was constructed using bimetallic metal-organic frameworks to degrade pharmaceuticals and personal care products (PPCPs). Mn-MIL-53(Fe) was successfully synthesised by adjusting the doping ratio of Mn using solvothermal method. The removal of ibuprofen (IBP) by UV/Mn-MIL-53(Fe)/PMS process was as high as 79.7% in 30 min with a Mn doping ratio of 1.0 (molar ratio of Mn to Fe), and the reaction rate constant was 26.9% higher than undoped. Mn-MIL-53(Fe) had been systematically characterized in terms of its physical structure, microscopic morphology, surface functional groups and photoelectric properties. The mechanism investigation revealed that the cycling of Mn and Fe accelerated the rate of electron transfer in the system, which significantly increased the activation efficacy of PMS to generate more hydroxyl and sulfate radicals for IBP degradation. A total of 13 transformation products were detected during the degradation of IBP by the UV/Mn-MIL-53(Fe)/PMS process. Theoretical calculations were used to predict the sites on the IBP molecule that were vulnerable to attack, and four possible degradation pathways were deduced. The excellent stability and efficient catalytic properties of Mn-MIL-53(Fe) provided a promising solution to the problem of water treatment contaminated with PPCPs.

Environmental risk assessment of pharmaceutical pollutants in the Oro River Sub-basin (Colombia).

Pharmaceuticals and Personal Care Compounds (PPCPs) are contaminants present in wastewater and in the receiving surface waters, which have no regulations and can bring on environmental risks. In this study, we evaluated the presence of six PPCPs in the Oro River Sub-basin (Colombia) and the environmental risk associated with them. We have verified that the monitored rivers show the presence of Ibuprofen, Cephalexin and Carbamazepine; the first ones (Ibuprofen and cephalexin) were those that presented higher concentrations since they are widely prescribed in Colombia. Pharmaceutical compound concentrations in the rivers downstream of the wastewater treatment plants from Floridablanca were higher than in other monitoring sites being a significant point source of contamination. This wastewater treatment plant receives hospital discharges from the city, including internationally recognized clinics accepting patients from different parts of the country. The environmental risk assessment showed that ibuprofen and Cephalexin have a higher impact on aquatic organisms.

Associations between over-the-counter analgesics usage and symptoms of anxiety and depression in adolescents: a network analysis.

BACKGROUND: The use of over-the-counter analgesics (OTCA) is common among adolescents and has been linked with increased symptoms of anxiety and depression. However, little is known about which specific symptoms are most strongly connected to OTCA usage. The current study assessed which anxiety and depression symptoms were most closely associated with OTCA usage in a large sample of adolescents and examined whether this differed across genders. METHOD: The present study was based on data from 626,581 participants from the Ungdata survey in Norway. Associations between OTCA and anxiety and depression symptoms were examined using network analysis. Non-regularized partial-correlation networks were constructed to estimate the conditional dependent relations between the use of OTCA and symptoms while controlling for pain. Gender-specific networks were created for comparison. RESULTS: OTCA usage was associated with most symptoms, even after controlling for pain, with the strongest associations with "sleep problems", "stiff or tense", "everything is a struggle" and "suddenly scared". There were some gender differences, showing that "sleep problems" and "hopeless" were more strongly related to OTCA usage in females, whereas "stiff or tense" was more strongly related to OTCA usage in males. CONCLUSION: Overall, the somatic symptoms of anxiety and depression displayed the strongest associations with OTCA usage. When examining the gender-specific networks, both showed similar trends, although males exhibited slightly stronger associations between OTCA usage and somatic symptoms.

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.