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1.
Chemosphere ; 286(Pt 3): 131849, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34426267

RESUMO

Ibuprofen (IBP) is one ubiquitous drug prescribed as anti-inflammatory, analgesic, and antipyretic. It has been detected in effluents of wastewater plant treatments, sewage sludge, hospital wastewaters, surface waters, and drinking water due to its continuous release to the environment, mainly from the excretion in the urine of animals and humans. IBP is a carcinogenic and non-steroidal endocrine disrupting drug with harmful effects over fungal, bacterial, algae, microorganisms, crustacean, and fish species, and can be potentially hazard for human health. Since conventional treatments remove inefficiently this drug, many advanced oxidation processes (AOPs) have been developed aiming their abatement from waters to avoid their harmful health problems. This paper presents an exhaustive and critical review on the application of AOPs to treat synthetic waters, natural waters, and real wastewaters polluted with IBP alone or mixed with other common drugs covering up to 2020. The characteristics and main results obtained for single, hybrid, and sequential treatments are described. Dielectric barrier or pulsed-corona discharges are detailed among the single processes. Hybrid processes such as photocatalysis (UV/H2O2, UV/chlorine, TiO2/UV), hybrid ozonation (O3/H2O2, electro-peroxone, catalytic ozonation), Fenton-based processes (photo-Fenton, electro-Fenton, photoelectro-Fenton), zero-valent iron, ultrasonic, peroxymonosulfate, and persulfate, are discussed. The effect of the kind of irradiation (UV, visible, solar) on photo-assisted processes is analyzed. Sequential processes with biological pre- or post-treatments using or not membranes for natural water and real wastewater remediation are described. Finally, 38 by-products detected during IBP removal by AOPs are reported, allowing envisaging three parallel pathways for its initial degradation.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Humanos , Peróxido de Hidrogênio , Ibuprofeno , Oxirredução , Águas Residuárias , Poluentes Químicos da Água/análise
2.
Water Sci Technol ; 84(9): 2158-2179, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34810303

RESUMO

In the present work, the performance of Ag/ZnO/CoFe2O4 magnetic photocatalysts in the photocatalytic degradation of ibuprofen (IBP) was evaluated. This study considered the use of pure Ag/ZnO (5% Ag) and also the use of the Ag/ZnO/CoFe2O4 magnetic catalysts containing different amounts (5, 10 and 15% wt) of cobalt ferrite (CoFe2O4). The catalysts were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and photoacoustic spectroscopy. To carry out the photocatalytic degradation reaction, different concentrations of the ibuprofen contaminant solution (10, 20 and 30 ppm) and different concentrations of photocatalyst were tested (0.3 g L-1, 0.5 g L-1 and 1.0 g L-1). The reaction parameters studied were: IBP concentration, catalyst concentration, adsorption and photolysis, influence of the matrix, radiation source (solar and artificial) and the effect of organic additive. At the end of the photocatalytic tests, the best operating conditions were defined. Considering the obtained results of degradation efficiency and magnetic separation, the optimal parameters selected to proceed with the other tests of the study were: ibuprofen solution concentration 10 ppm, Ag/ZnO/CoFe2O4 (5%) catalyst at a concentration of 0.3 g L-1 and pH 4.5 of the reaction medium. The results indicated the feasibility of magnetic separation of the synthesized catalysts. A long duration test indicated that the catalyst exhibits stability throughout the degradation reaction, as more than 80% of IBP was degraded after 300 minutes. The photocatalytic activity was directly affected by the ferrite load. The higher the nominal load of ferrite, the lower the performance in IBP degradation. It was also observed that the smallest amount of ferrite studied was enough for the catalyst to be recovered and reused. The adsorption and photolysis tests did not show significant results in the IBP degradation. In addition, it was possible to verify that the aqueous matrix, the use of solar radiation and the addition of additive (acid formic) were interfered directly in the process. The catalyst reuse tests indicated that it can be recovered and reused at least three times without considerable catalytic activity loss.


Assuntos
Poluentes Químicos da Água , Óxido de Zinco , Catálise , Ibuprofeno , Fotólise , Luz Solar , Poluentes Químicos da Água/análise
3.
Braz Dent J ; 32(3): 105-115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34755785

RESUMO

This clinical trial evaluated the effect of the coadministration of ibuprofen/caffeine on bleaching-induced tooth sensitivity (TS). A triple-blind, parallel-design, randomized clinical trial was conducted on 84 patients who received ibuprofen/caffeine or placebo capsules. The drugs were administered for 48 hours, starting 1 hour before the in-office bleaching. Two bleaching sessions were performed with 35% hydrogen peroxide gel with 1-week interval. TS was recorded up to 48 hours after dental bleaching with a 0-10 visual analogic scale (VAS) and a 5-point numeric rating scale (NRS). The color was evaluated with VITA Classical and VITA Bleachedguide scales (ΔSGU) and VITA Easyshade spectrophotometer (ΔE*ab and ΔE00). The absolute risk of TS in both groups was evaluated using Fischer's exact test. Comparisons of the TS intensity (NRS and VAS data) were performed by using the Mann-Whitney test and a two-way repeated measures ANOVA, respectively. The color alteration between the groups was compared with the Student's t test. The significance level was 5%. There was no statistically significant difference between the groups for the absolute risk of TS (p = 1.00) or for the intensity of TS (p > 0.05). A bleaching of approximately 7 shade guide units was observed on the Vita Classical and Vita Bleachedguide scales, with no statistical difference between the groups. It was concluded that coadministration of ibuprofen and caffeine did not reduce the absolute risk or intensity of TS and did not interfere with the efficacy of dental bleaching.


Assuntos
Cafeína/uso terapêutico , Sensibilidade da Dentina , Ibuprofeno/uso terapêutico , Clareadores Dentários , Clareamento Dental , Sensibilidade da Dentina/induzido quimicamente , Humanos , Peróxido de Hidrogênio , Clareadores Dentários/efeitos adversos , Resultado do Tratamento
4.
AAPS PharmSciTech ; 22(8): 268, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750731

RESUMO

Particle size distribution (PSD) is often considered as critical material attribute for active pharmaceutical ingredients (APIs), and the need for regular evaluation stands as an important quality control parameter in the pharmaceutical industry. Near-infrared (NIR) spectroscopy, used routinely for API identification, was introduced as analytical tool for simultaneous determination of particle size of ibuprofen. The demonstrated potential was highlighted by the development of rapid, robust, and noninvasive method coupled with multivariate data analysis (MVA), which can be easily transferred in QC laboratories for routine analysis. Principal component analysis (PCA) and partial least squares (PLS) regression analyses were performed on a calibration set of 61 ibuprofen samples, which differed in their median particle size Dv(50). The score scatterplots revealed evident clustering of ibuprofen samples according to their particle size, as well as occurrence of a distinctive outlying group of ibuprofen samples originating from one manufacturer. Further testing by means of mid-infrared spectroscopy, X-ray powder diffraction, and particle morphology analysis pinpointed particle morphology being responsible for the observed outlying group. Consequently, PLS class modeling based on particle morphology was introduced, which delivered two separate PLS regression models: one for blade-like ibuprofen crystals and another for irregular plate-like ibuprofen crystals. The former regression model exhibited high correlation coefficients and satisfactory predictive power (R2X = 0.999, R2Y = 0.917, Q2 = 0.901), whereas the latter demonstrated lower statistical indicators (R2X = 0.99, R2Y = 0.72, Q2 = 0.55). Additionally, the study underlines the importance of particle shape evaluation and sample classification according to particle morphology similarity prior to building NIRS-based regression models for PSD determination.


Assuntos
Ibuprofeno , Espectroscopia de Luz Próxima ao Infravermelho , Análise dos Mínimos Quadrados , Tamanho da Partícula , Pós
5.
Sensors (Basel) ; 21(21)2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34770608

RESUMO

Highly stable, small-sized and evenly distributed solid mercury nanoparticles capped with ibuprofen (Ibu-HgNPs) were prepared via reduction with hydrazine and capped with ibuprofen as a stabilizing agent. Characterization of Ibu-HgNPs was carried out by UV-Vis spectrophotometry and transmission electron microscopy (TEM). The prepared Ibu-HgNPs were immobilized onto a glassy carbon electrode (GCE) and used for the first time as the sensing element for voltammetric determination of low concentrations of acrylamide (AA) in aqueous solutions. Various parameters such as the type of supporting electrolyte, voltammetric mode, frequency, deposition time, stirring rate and initial potential were optimized to obtain the highest peak current of AA. The sensor delivered the best results in combination with the square wave voltammetry (SWV) mode, with good repeatability (relative standard deviation (RSD) of 25 repetitions was 1.4% for 1000 ppb AA). The study further revealed that Ibu-HgNPs are strongly adhered to GCE and hence do not contaminate the environment even after several runs. The newly developed AA sensor provides linear calibration dependence in the range of 100-1300 ppb with an R2 value of 0.996 and limit of detection (LOD) of 8.5 ppb. Negligible interference was confirmed from several organic compounds, cations and anions. The developed sensor was successfully applied for AA determination in various types of environmental real water samples to prove its practical usefulness and applicability.


Assuntos
Mercúrio , Nanopartículas , Acrilamida , Técnicas Eletroquímicas , Eletrodos , Ibuprofeno
6.
Molecules ; 26(19)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34641365

RESUMO

On account of the rigid structure of alginate chains, the oxidation-reductive amination reaction was performed to synthesize the reductive amination of oxidized alginate derivative (RAOA) that was systematically characterized for the development of pharmaceutical formulations. The molecular structure and self-assembly behavior of the resultant RAOA was evaluated by an FT-IR spectrometer, a 1H NMR spectrometer, X-ray diffraction (XRD), thermal gravimetric analysis (TGA), a fluorescence spectrophotometer, rheology, a transmission electron microscope (TEM) and dynamic light scattering (DLS). In addition, the loading and in vitro release of ibuprofen for the RAOA microcapsules prepared by the high-speed shearing method, and the cytotoxicity of the RAOA microcapsules against the murine macrophage RAW264.7 cell were also studied. The experimental results indicated that the hydrophobic octylamine was successfully grafted onto the alginate backbone through the oxidation-reductive amination reaction, which destroyed the intramolecular hydrogen bond of the raw sodium alginate (SA), thereby enhancing its molecular flexibility to achieve the self-assembly performance of RAOA. Consequently, the synthesized RAOA displayed good amphiphilic properties with a critical aggregation concentration (CAC) of 0.43 g/L in NaCl solution, which was significantly lower than that of SA, and formed regular self-assembled micelles with an average hydrodynamic diameter of 277 nm (PDI = 0.19) and a zeta potential of about -69.8 mV. Meanwhile, the drug-loaded RAOA microcapsules had a relatively high encapsulation efficiency (EE) of 87.6 % and good sustained-release properties in comparison to the drug-loaded SA aggregates, indicating the good affinity of RAOA to hydrophobic ibuprofen. The swelling and degradation of RAOA microcapsules and the diffusion of the loaded drug jointly controlled the release rate of ibuprofen. Moreover, it also displayed low cytotoxicity against the RAW264.7 cell, similar to the SA aggregates. In view of the excellent advantages of RAOA, it is expected to become the ideal candidate for hydrophobic drug delivery in the biomedical field.


Assuntos
Alginatos/química , Aminas/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Ibuprofeno/administração & dosagem , Macrófagos/efeitos dos fármacos , Aminação , Animais , Ibuprofeno/química , Camundongos , Micelas , Estrutura Molecular , Células RAW 264.7
7.
Drug Discov Ther ; 15(5): 278-280, 2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34707073

RESUMO

To help stop the coronavirus disease 2019 (COVID-19) pandemic, vaccines are currently the most critical tool. However, the COVID-19 mRNA vaccines frequently cause systemic side effects shortly after the injection, such as fever, headache and generalized fatigue. In our survey, after receiving the second dose of the COVID-19 vaccine, 80% developed fever, 62% headache and 69% generalized fatigue. Among people who required antipyretics, the average durations of fever and headache were significantly shorter in those who took non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, loxoprofen and ibuprofen, than those who took acetaminophen. In our patch-clamp studies, NSAIDs effectively suppressed the delayed rectifier K+-channel (Kv1.3) currents in T-lymphocytes and thus exerted immunosuppressive effects. Because of this pharmacological property, the use of NSAIDs should be more effective in reducing the vaccine-induced systemic side effects that are caused primarily by the enhanced cellular immunity.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Vacinas contra COVID-19/efeitos adversos , Imunossupressores/uso terapêutico , Acetaminofen/uso terapêutico , Adolescente , Aspirina/uso terapêutico , Fadiga/tratamento farmacológico , Fadiga/etiologia , Febre/tratamento farmacológico , Febre/etiologia , Cefaleia/tratamento farmacológico , Cefaleia/etiologia , Humanos , Ibuprofeno/uso terapêutico , Técnicas de Patch-Clamp , Fenilpropionatos/uso terapêutico , Adulto Jovem
8.
Analyst ; 146(22): 6874-6882, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34633393

RESUMO

As the use of non-steroidal anti-inflammatory drugs (NSAIDS) increases, their side effects have also attracted attention. Ibuprofen is one of the most widely-used NSAIDs. In this study, we screened the highly-sensitive and specific antibody 6E10, with an IC50 of 1.92 ng mL-1, and a linear range of 0.53-6.97 ng mL-1. In this study, we developed a rapid lateral flow immunochromatographic assay (ICA) strip method to detect ibuprofen in water or herbal tea. The cut-off limit of the strip is 10 ng mL-1 in water, and concentrations as low as 1 ng mL-1 can be detected in herbal tea samples, with the results obtained by the naked eye within 6 min. All the data were confirmed by high performance liquid chromatography-quadrupole time of flight-mass spectrometry (HPLC-QTOF-MS). This lateral-flow ICA strip is thus a rapid tool for on-site detection and screening of ibuprofen in water and herbal tea.


Assuntos
Ibuprofeno , Chás de Ervas , Cromatografia de Afinidade , Limite de Detecção , Água
9.
Molecules ; 26(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34641337

RESUMO

We report the design and synthesis of a series of new 5-chloropyridinyl esters of salicylic acid, ibuprofen, indomethacin, and related aromatic carboxylic acids for evaluation against SARS-CoV-2 3CL protease enzyme. These ester derivatives were synthesized using EDC in the presence of DMAP to provide various esters in good to excellent yields. Compounds are stable and purified by silica gel chromatography and characterized using 1H-NMR, 13C-NMR, and mass spectral analysis. These synthetic derivatives were evaluated in our in vitro SARS-CoV-2 3CLpro inhibition assay using authentic SARS-CoV-2 3CLpro enzyme. Compounds were also evaluated in our in vitro antiviral assay using quantitative VeroE6 cell-based assay with RNAqPCR. A number of compounds exhibited potent SARS-CoV-2 3CLpro inhibitory activity and antiviral activity. Compound 9a was the most potent inhibitor, with an enzyme IC50 value of 160 nM. Compound 13b exhibited an enzyme IC50 value of 4.9 µM. However, it exhibited a potent antiviral EC50 value of 24 µM in VeroE6 cells. Remdesivir, an RdRp inhibitor, exhibited an antiviral EC50 value of 2.4 µM in the same assay. We assessed the mode of inhibition using mass spectral analysis which suggested the formation of a covalent bond with the enzyme. To obtain molecular insight, we have created a model of compound 9a bound to SARS-CoV-2 3CLpro in the active site.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , COVID-19/tratamento farmacológico , Proteases 3C de Coronavírus/antagonistas & inibidores , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , SARS-CoV-2/efeitos dos fármacos , Animais , Antivirais/química , Antivirais/farmacologia , Chlorocebus aethiops , Proteases 3C de Coronavírus/metabolismo , Ésteres/química , Ésteres/farmacologia , Halogenação , Humanos , Ibuprofeno/análogos & derivados , Ibuprofeno/farmacologia , Indometacina/análogos & derivados , Indometacina/farmacologia , Simulação de Acoplamento Molecular , Piridinas/química , Piridinas/farmacologia , SARS-CoV-2/metabolismo , Ácido Salicílico/química , Ácido Salicílico/farmacologia , Células Vero
10.
BMC Pediatr ; 21(1): 457, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34663266

RESUMO

BACKGROUND: Optimal management of haemodynamically significant patent ductus arteriosus (HsPDA) in premature babies remains controversial. Our aim is to compare death and/or adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants with HsPDA who were managed with conservative [C], medical [M] and/or surgical [S] treatment, with secondary aim to examine short-term morbidities among [S] and [C] groups. The study also compared outcomes in very low birth weight (VLBW) infants with HsPDA and non-HsPDA. METHODS: A retrospective study of VLBW preterm infants born before 29 weeks in Singapore from 2007 to 2016 was conducted. RESULTS: A total of 474 VLBW infants were admitted in NUH from 2007 to 2016. Infants aged between 24 + 0 and 28 + 6 weeks of gestation, weighing ≤1500 g and diagnosed with patent ductus arteriosus (PDA) were included in the study, of which 172 infants (124 HsPDA and 48 non-HsPDA) were analyzed. Among infants with HsPDA, 17 infants were managed with [C], 83 with [M] and 24 with [S]. Mortality was not increased regardless of the presence of HsPDA or treatment received. Infants with non-HsPDA were less likely to have isolated speech delay (p < 0.05), but not global developmental delay (GDD). No significant differences in neurodevelopmental outcomes such as hearing loss, cerebral palsy (CP) and speech delay were found. [M + S] infants were at a higher risk of developing chronic lung disease (CLD) (OR 6.83, p < 0.05) and short-term growth failure compared to [C] infants. They were significantly shorter and had a smaller head circumference at discharge (p < 0.05). [M + S] infants also had elevated creatinine compared to those in group [C] (81.1 ± 24.1 vs 48.3 ± 11.8 umol/L, p < 0.000). CONCLUSIONS: Compared to conservative management, infants requiring [M + S] treatment for HsPDA were more likely to have short-term complications such as CLD, elevated creatinine, and poorer growth. Despite a more turbulent postnatal course, death and/or adverse neurodevelopmental outcomes were not worse in infants managed with [M + S].


Assuntos
Permeabilidade do Canal Arterial , Permeabilidade do Canal Arterial/terapia , Humanos , Ibuprofeno , Lactente , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Recém-Nascido Prematuro , Estudos Retrospectivos
11.
BMJ Open ; 11(10): e048531, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645660

RESUMO

INTRODUCTION: Low back pain (LBP) is among the top three most common diseases worldwide, resulting in a life with pain-related disability. To date, no study has assessed the efficacy of metamizole (dipyrone), a non-opioid analgesic and antipyretic prodrug compared with the conventional non-steroidal anti-inflammatory drug ibuprofen, in patients with an acute LBP episode. Further, it is unclear, whether a short educational intervention is superior to usual care alone. OBJECTIVES: The objective of this study is to assess first, whether metamizole is non-inferior to ibuprofen in a new episode of acute or subacute LBP. Second, we aim to assess whether a short educational intervention including evidence-based patient information on the nature of LBP is superior to usual care alone. METHODS AND ANALYSIS: An investigator-initiated multicentre, randomised, double blind trial using a factorial design will be performed. A total of 120 participants with a new episode of LBP will be recruited from GP practices, outpatient clinics and from emergency departments, and randomised into four different treatment groups: ibuprofen alone, ibuprofen and short intervention, metamizole alone, metamizole and short intervention. The primary endpoint for the medical treatment will be change in pain assessed on an 11-point Numeric Rating Scale after 14 days. The primary outcome for the short intervention will be change in the Core Outcome Measures Index assessed after 42 days. ETHICS, DISSEMINATION AND FUNDING: This study has been approved by the responsible Ethics Board (Ethikkommission Bern/2018-01986) and the Swiss Agency for Therapeutic Products (Swissmedic/2019DR4002). Results will be published in open access policy peer-reviewed journals. The study is funded by the Swiss National Science Foundation (grant number 32 003B-179346). TRIAL REGISTRATION NUMBER: NCT04111315.


Assuntos
Analgésicos não Narcóticos , Dor Lombar , Dipirona/uso terapêutico , Método Duplo-Cego , Humanos , Ibuprofeno/uso terapêutico , Dor Lombar/tratamento farmacológico , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
BMC Pediatr ; 21(1): 466, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34674670

RESUMO

BACKGROUND: Correction surgery for cleft palate is recommended between 9 and 18 months of age. Patients suffer from acute pain after palatoplasty. Clinicians are hesitant to use opioids for analgesia concerning the potential high risk of respiratory adverse events. Intravenous ibuprofen perhaps be a suitable adjuvant to pain relief. We try to assess whether preoperative administration of intravenous ibuprofen can decrease opioid requirements following cleft palate repair in infants. METHODS: This single center prospective randomized clinical trial was performed from February to April 2021 at Department of Anesthesiology in Shanghai Children's Medical Center. Forty patients ASA I-II, aged 9-24 months with isolated cleft palate and undergoing palatoplasty were randomized in a 1:1 ratio to receive either a single dose of 10 mg/kg ibuprofen intravenously or normal saline at induction. Children and infants postoperative pain scale (CHIPPS) was used for pain assessment. Those patients CHIPPS pain score equal or higher than 4 received analgesic rescue with titrating intravenous fentanyl 0.5 µg/kg and repeated in 10 min if required. The primary outcome was the amount of postoperative fentanyl used for rescue analgesia in postanesthesia care unit (PACU). RESULTS: Patients (n = 20 in each group) in IV-Ibuprofen group required less postoperative fentanyl than those in placebo group (p<0.001). There was no significant difference between two groups in first rescue analgesia time (p = 0.079) and surgical blood loss (p = 0.194). No incidence of obvious adverse events had been found within the first 24 h after surgery in both groups. CONCLUSIONS: Preemptive intravenous administration ibuprofen 10 mg/kg at induction had a significant opioid sparing effect in early postoperative period without obvious adverse effects in infants undergoing palatoplasty. TRIAL REGISTRATION: CHICTR, CTR2100043718, 27/02/2021 http://www.chictr.org.cn/showproj.aspx?proj=122187.


Assuntos
Fissura Palatina , Ibuprofeno , Administração Intravenosa , Analgésicos , Criança , China , Fissura Palatina/cirurgia , Método Duplo-Cego , Humanos , Ibuprofeno/uso terapêutico , Lactente , Estudos Prospectivos
13.
PLoS One ; 16(9): e0257021, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34499688

RESUMO

OBJECTIVE: To compare the effectiveness and safety of prescribing ibuprofen and oxycodone for at-home management of children's fracture pain. METHODS: A prospective observational cohort was conducted at the Stollery Children's Hospital pediatric emergency department (June 2010-July 2014). Children aged 4-16 years with an isolated fracture discharged home with advice to use either ibuprofen or oxycodone were recruited. RESULTS: A cohort of 329 children (n = 217 ibuprofen, n = 112 oxycodone) were included. Mean age was 11.1 years (SD 3.5); 68% (223/329) were male. Fracture distribution included 80.5% (264/329) upper limb with 34.3% (113/329) requiring fracture reduction. The mean reduction in Faces Pain Score-Revised score (maximum pain-post-treatment pain) for Day 1 was 3.6 (SD 1.9) (ibuprofen) and 3.8 (SD 2.1) (oxycodone) (p = 0.50); Day 2 was 3.6 (SD 1.8) (ibuprofen) and 3.7 (SD 1.6) (oxycodone) (p = 0.56); Day 3 was 3.7 (SD 1.7) (ibuprofen) and 3.3 (SD 1.7) (oxycodone) (p = 0.24). Children prescribed ibuprofen (51.2%, 109/213) experienced less adverse events compared to those prescribed oxycodone (70.5% 79/112) on Day 1 (p = 0.001). Children prescribed ibuprofen (71.8%, 150/209) had their function (eat, play, school, sleep) affected less than those prescribed oxycodone (83.0%, 93/112) (p = 0.03) on Day 1. CONCLUSION: Children prescribed ibuprofen or oxycodone experienced similar analgesic effectiveness for at-home fracture pain. Oxycodone prescribing was associated with more adverse events and negatively impacted function. Oxycodone use does not appear to confer any benefit over ibuprofen for pain relief and has a negative adverse effect profile. Ibuprofen appears to be a safe option for fracture-related pain.


Assuntos
Analgésicos não Narcóticos/administração & dosagem , Fraturas Ósseas/tratamento farmacológico , Ibuprofeno/administração & dosagem , Oxicodona/administração & dosagem , Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Adolescente , Analgésicos não Narcóticos/efeitos adversos , Analgésicos Opioides , Criança , Pré-Escolar , Estudos de Coortes , Método Duplo-Cego , Serviço Hospitalar de Emergência , Feminino , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/patologia , Humanos , Ibuprofeno/efeitos adversos , Masculino , Oxicodona/efeitos adversos , Manejo da Dor , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/patologia
14.
Environ Toxicol Pharmacol ; 88: 103749, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34547448

RESUMO

We developed phospho-ERK1/2 ELISA for human and rainbow trout liver cells, employing HepG2 and RTL-W1 cell lines as models. The assay was applied to detect changes in ERK1/2 activity for nine chemicals, added over a wide concentration range and time points. Cell viability was measured to separate ERK1/2 regulation from cytotoxicity. Perfluorooctane sulfonate and carbendazim did not change ERK1/2 activity; influence on ERK1/2 due to cytotoxicity was indicated for tributyltin and cypermethrin. Mancozeb, benzo[a]pyrene, and bisphenol A stimulated ERK1/2 up to ∼2- (HepG2) and 1.5 (RTL-W1)-fold, though the kinetics differed between chemicals and cell lines. Bisphenol A and benzo[a]pyrene were the most potent concentration-wise, altering ERK1/2 activity in pM (HepG2) to nM (RTL-W1) range. While atrazine and ibuprofen increased ERK1/2 activity by ∼2-fold in HepG2, they did not initiate an appreciable response in RTL-W1. This assay proved to be a sensitive, medium- to high-throughput tool for detecting unrecognized ERK1/2-disrupting chemicals.


Assuntos
Fígado/citologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Ácidos Alcanossulfônicos/toxicidade , Animais , Atrazina/toxicidade , Compostos Benzidrílicos/toxicidade , Benzimidazóis/toxicidade , Benzo(a)pireno/toxicidade , Carbamatos/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fluorcarbonetos/toxicidade , Humanos , Ibuprofeno/toxicidade , Maneb/toxicidade , Oncorhynchus mykiss , Fenóis/toxicidade , Fosforilação/efeitos dos fármacos , Piretrinas/toxicidade , Compostos de Trialquitina/toxicidade , Zineb/toxicidade
15.
Cochrane Database Syst Rev ; 9: CD013264, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499349

RESUMO

BACKGROUND: Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, may reduce the incidence and severity of opioid-induced adverse events (AEs). OBJECTIVES: To assess the analgesic efficacy and adverse effects of single-dose intravenous (IV) ibuprofen, compared with placebo or an active comparator, for moderate-to-severe postoperative pain in adults. SEARCH METHODS: We searched the following databases without language restrictions: CENTRAL, MEDLINE, Embase and LILACS on 10 June 2021. We checked clinical trials registers and reference lists of retrieved articles for additional studies. SELECTION CRITERIA: We included randomized trials that compared a single postoperative dose of intravenous (IV) ibuprofen with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for review inclusion, assessed risk of bias, and extracted data. Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a 4- and 6-hour period. Our secondary outcomes were time to, and number of participants using rescue medication; withdrawals due to lack of efficacy, adverse events (AEs), and for any other cause; and number of participants reporting or experiencing any AE, serious AEs (SAEs), and specific NSAID-related or opioid-related AEs. We were not able to carry out any planned meta-analysis. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: Only one study met our inclusion criteria, involving 201 total participants, mostly female (mean age 42 years), undergoing primary, unilateral, distal, first metatarsal bunionectomy (with osteotomy and internal fixation). Ibuprofen 300 mg, placebo or acetaminophen 1000 mg was administered intravenously to participants reporting moderate pain intensity the day after surgery. Since we identified only one study for inclusion, we did not perform any quantitative analyses. The study was at low risk of bias for most domains. We downgraded the certainty of the evidence due to serious study limitations, indirectness and imprecision. Ibuprofen versus placebo Findings of the single study found that at both the 4-hour and 6-hour assessment period, the proportion of participants with at least 50% pain relief was 32% (24/76) for those assigned to ibuprofen and 22% (11/50) for those assigned to placebo. These findings produced a risk ratio (RR) of 1.44 (95% confidence interval (CI) 0.77 to 2.66 versus placebo for at least 50% of maximum pain relief over the 4-hour and 6-hour period (very low-certainty evidence). Median time to rescue medication was 101 minutes for ibuprofen and 71 minutes for placebo (1 study, 126 participants; very low-certainty evidence). The number of participants using rescue medication was not reported within the included study. During the study (1 study, 126 participants), 58/76 (76%) of participants assigned to ibuprofen and 39/50 (78%) assigned to placebo reported or experienced any adverse event (AE), (RR 0.98, 95% CI 0.81 to 1.19; low-certainty evidence). No serious AEs (SAEs) were experienced (1 study, 126 participants; very low-certainty evidence). Ibuprofen versus active comparators Ibuprofen (300 mg) was similar to the active comparator, IV acetaminophen (1000 mg) at 4 hours and 6 hours (1 study, 126 participants). For those assigned to active control (acetaminophen), the proportion of participants with at least 50% pain relief was 35% (26/75) at 4 hours and 31% (23/75) at 6 hours. At 4 hours, these findings produced a RR of 0.91 (95% CI 0.58 to 1.43; very low-certainty evidence) versus active comparator (acetaminophen). At 6 hours, these findings produced a RR of 1.03 (95% CI 0.64 to 1.66; very low-certainty evidence) versus active comparator (acetaminophen). Median time to rescue medication was 101 minutes for ibuprofen and 125 minutes for the active comparator, acetaminophen (1 study, 151 participants; very low-certainty evidence). The number of participants using rescue medication was not reported within the included study. During the study, 8/76 (76%) of participants assigned to ibuprofen and 45/75 (60%) assigned to active control (acetaminophen) reported or experienced any AE, (RR 1.27, 95% CI 1.02 to 1.59; very low-certainty evidence). No SAEs were experienced (1 study, 151 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the suggestion that IV ibuprofen is effective and safe for acute postoperative pain in adults.


Assuntos
Dor Aguda , Ibuprofeno , Acetaminofen/uso terapêutico , Dor Aguda/tratamento farmacológico , Adulto , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Feminino , Humanos , Ibuprofeno/efeitos adversos , Masculino , Dor Pós-Operatória/tratamento farmacológico
16.
J Chromatogr A ; 1655: 462520, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34517164

RESUMO

A high-performance version of in-line, three-phase direct immersion-single drop microextraction (DI-SDME) coupled with capillary electrophoresis (CE) was demonstrated using a commercial CE instrument, and all the major and minor details were described to provide an easy-to-follow and user-friendly protocol. The excellent sample cleanup and enrichment power of this method was demonstrated with nonsteroidal anti-inflammatory drugs (NSAIDs) in human urine. The only preparation of urine samples was the addition of HCl to acidify the urine sample to pH 2. The acidic NSAIDs in the acidified urine sample were extracted into a basic acceptor drop covered with a thin organic layer attached to the inlet tip of a capillary immersed in the sample. A simple but powerful DI-SDME-CE method could be carried out automatically without any modification of the existing CE instrument. For improved performance, sample agitation and heating were employed by installing a microstirrer and a thermostating jacket in the sample tray. With 10 min of DI-SDME at 35°C with stirring, NSAIDs such as ketoprofen, ibuprofen, and naproxen in urine were enriched 340-970-fold with intraday and interday RSDs of 0.8-2.4% and 1.1-3.6%, respectively. The LODs obtained with in-line coupled CE/UV were 10-50 nM (2-10 µg/L). The performance of DI-SDME-CE/UV was also demonstrated by determining the naproxen level in human urine collected 24 h after taking a single oral dose of the drug. The spike recovery of naproxen from a single-point standard addition to the urine sample was 80%. Our high-performance three-phase DI-SDME-CE method is quite promising for the analysis of ionizable trace analytes in a complex sample matrix.


Assuntos
Eletroforese Capilar , Cetoprofeno , Anti-Inflamatórios não Esteroides , Humanos , Ibuprofeno , Naproxeno
17.
Nihon Shokakibyo Gakkai Zasshi ; 118(9): 840-850, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34511551

RESUMO

BACKGROUND & AIMS: Capsule endoscopy has revealed that nonsteroidal anti-inflammatory drugs may cause damage not only to the stomach but also to the small intestine, which has become one of the most serious issues in gastroenterology. However, few studies have reported the effect of ibuprofen (IBP), which is widely prescribed worldwide, on the small intestine, and it remains unclear whether IBP can cause small intestinal damage. We have previously shown that acetaminophen (APAP), which is used as an antipyretic/analgesic drug, inhibits IBP-induced gastric damage by suppressing matrix metalloprotease-13 (MMP-13) gene expression. In this study, we investigated the ability of IBP to induce small intestinal damage and the efficacy of APAP against IBP-induced small intestinal damage in rats. MAIN METHODS: Nonfasted male Sprague-Dawley rats were orally administered with IBP (200mg/kg) and then euthanized at various time points (0, 4, 8, 16, and 24h) after the administration. The small intestine, jejunum, and ileum were removed, and intestinal lesions were measured. To elucidate the efficacy of APAP against IBP-induced small intestinal damage, the rats were treated with IBP (200mg/kg) with or without APAP (200mg/kg), and small intestinal damage was evaluated 24h after the administration. Moreover, the expression levels of GAPDH, TNFα, iNOS, and MMP-13 genes were determined at various time points (8, 16, and 24h) by RT-qPCR. KEY FINDINGS: The oral administration of IBP induced obvious small intestinal damage, which was found to be significant at 24h (p<0.05 vs 0h, Dunnett's test). The coadministration of APAP significantly prevented IBP-induced damage (p<0.05, Student's t-test). In addition, the expression levels of TNFα and iNOS genes were significantly increased by IBP (p<0.01 and p<0.05 vs. vehicle, respectively, Tukey-Kramer test), whereas the cotreatment with APAP suppressed the increases at 8h. Moreover, compared with the vehicle, the IBP treatment significantly increased the expression level of the MMP-13 gene (p<0.01) at each time point (8, 16, and 24h, Tukey-Kramer test), whereas the APAP cotreatment significantly suppressed the increase (p<0.01 vs. IBP at 8h, p<0.05 vs. IBP at 16 and 24h, Tukey-Kramer test). CONCLUSIONS: This study suggested that a single administration of IBP was associated with the risk of inducing small intestinal ulcers in rats, and APAP could prevent IBP-induced small intestinal damage by suppressing the MMP-13 gene expression.


Assuntos
Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Acetaminofen/toxicidade , Animais , Ibuprofeno/farmacologia , Intestino Delgado , Fígado , Masculino , Metaloproteinase 13 da Matriz/genética , Ratos , Ratos Sprague-Dawley
18.
Water Res ; 204: 117600, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34488141

RESUMO

The electro-hybrid ozonation-coagulation process (E-HOC) integrates electrocoagulation (EC) and ozonation simultaneously in a single unit. Nevertheless, the performance of the EC process is highly dependent on the polar connection configuration (monopolar vs. bipolar connection) and the type of generated coagulants (single-coagulant vs. dual-coagulants). In this study, the removal efficiency of the E-HOC process with different connection configurations and types of coagulants was assessed. The E-HOC process with bipolar connection (BE-HOC) exhibited higher removal efficiency for wastewater treatment plant (WWTP) effluent organic matter and ibuprofen (IBP) compared with the E-HOC process with monopolar connection (ME-HOC). Furthermore, dual-coagulant generation (released from both Al and Fe electrodes) in the BE-HOC process greatly improved the WWTP effluent organic matter and IBP removal efficiency. Lower energy consumption was observed for the BE-HOC process compared with the ME-HOC process. It was found that ozonation promoted the polymerization reactions during coagulant hydrolyzis in the E-HOC process. Compared with the ME-HOC process, the BE-HOC configuration and dual-coagulant mode further facilitated polymeric hydrolyzed coagulant species formation, thereby improving ozone catalytic and coagulation performance. According to trapping experiments and EPR analysis, •OH formation was enhanced in the BE-HOC process and dual-coagulant mode. In addition, more active reaction sites of generated hydrolyzed coagulant species were observed with bipolar connection and in the dual-coagulant generation mode based on X-ray photoelectron spectroscopy (XPS) analysis.


Assuntos
Ozônio , Poluentes Químicos da Água , Purificação da Água , Eletrodos , Ibuprofeno , Poluentes Químicos da Água/análise
19.
Water Res ; 204: 117647, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34536687

RESUMO

Understanding the in-sewer stability of analgesic biomarkers is important for interpreting wastewater-based epidemiology (WBE) data to estimate community-wide analgesic drugs consumption. The in-sewer stability of a suite of 19 analgesics and their metabolites was assessed using lab-scale sewer reactors. Target biomarkers were spiked into wastewater circulating in simulated gravity, rising main and control (no biofilm) sewer reactors. In-sewer transformation was observed over a hydraulic retention time of 12 h. All investigated biomarkers were stable under control reactor conditions. In gravity sewer conditions, diclofenac, desmetramadol, ibuprofen carboxylic acid, ketoprofen, lidocaine and tapentadol were highly stable (0-20% transformation in 12 h). Valdecoxib, parecoxib, etoricoxib, indomethacin, naltrexone, naloxone, piroxicam, ketoprofen, lidocaine, tapentadol, oxymorphone, hydrocodone, meperidine, hydromorphone were considered as moderately stable biomarkers (20-50% transformation in 12 h). Celecoxib and sulindac were considered unstable biomarkers (>50% transformation in 12 h). Ketoprofen, lidocaine, tapentadol, meperidine, hydromorphone were transformed to 0-20% whereas diclofenac, desmetramadol, ibuprofen carboxylic acid, valdecoxib, parecoxib, etoricoxib, indomethacin, naltrexone, piroxicam were transformed up to 20-50% in 12 h in rising main reactor (RMR). These biomarkers were considered as highly stable and stable biomarkers in RMR, respectively. Sulindac, celecoxib, naloxone, oxymorphone and hydrocodone were transformed more than 50% in 12 h and considered as unstable biomarkers in RMR. This study provides the information for a better understanding of the in-sewer loss of the analgesics before using them in WBE biomarkers for estimating drug loads at the population level.


Assuntos
Analgésicos , Cetoprofeno , Ácidos Carboxílicos , Diclofenaco , Ibuprofeno
20.
Trials ; 22(1): 627, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526095

RESUMO

BACKGROUND: Controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants. A persistent PDA is associated with neonatal mortality and morbidity, but causality remains unproven. Although both pharmacological and/or surgical treatment are effective in PDA closure, this has not resulted in an improved neonatal outcome. In most preterm infants, a PDA will eventually close spontaneously, hence PDA treatment potentially increases the risk of iatrogenic adverse effects. Therefore, expectant management is gaining interest, even in the absence of convincing evidence to support this strategy. METHODS/DESIGN: The BeNeDuctus trial is a multicentre, randomised, non-inferiority trial assessing early pharmacological treatment (24-72 h postnatal age) with ibuprofen versus expectant management of PDA in preterm infants in Europe. Preterm infants with a gestational age of less than 28 weeks and an echocardiographic-confirmed PDA with a transductal diameter of > 1.5 mm are randomly allocated to early pharmacological treatment with ibuprofen or expectant management after parental informed consent. The primary outcome measure is the composite outcome of mortality, and/or necrotizing enterocolitis Bell stage ≥ IIa, and/or bronchopulmonary dysplasia, all established at a postmenstrual age of 36 weeks. Secondary short-term outcomes are comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. This statistical analysis plan focusses on the short-term outcome and is written and submitted without knowledge of the data. TRIAL REGISTRATION: ClinicalTrials.gov NTR5479. Registered on October 19, 2015, with the Dutch Trial Registry, sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28.


Assuntos
Permeabilidade do Canal Arterial , Pré-Escolar , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/terapia , Humanos , Ibuprofeno/efeitos adversos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Conduta Expectante
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