Non-steroidal Anti-inflammatory Drugs Naproxen Research Articles

Combining naproxen and a dual amylin and calcitonin receptor agonist improves pain and structural outcomes in the collagen-induced arthritis rat model

BackgroundPain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction when administered alone. KBPs (Key Bioscience peptides) are synthetic peptides based on salmon calcitonin and are expected to inhibit bone resorption and to be chondroprotective. In this study, we investigated if combining a standard of care NSAID (naproxen) with a KBP resulted in improvement in pain scores, as well as disease activity and structural damage in a rat model of RA.MethodsCollagen-induced arthritis (CIA) was induced in 40 female Lewis rats by immunization with porcine type II collagen; 10 rats were given sham injections. CIA rats were treated with KBP and/or naproxen. Health scores and joint scores were evaluated daily. Mechanical and cold allodynia tests and burrowing tests were used to assess pain-like behaviors. Blood samples were collected for biomarker testing, and paws were collected for histology and microcomputed tomography.ResultsNaproxen monotherapy increased the time until humane endpoints was reached, and improved health score, pain assessments, and trabecular thickness, while KBP monotherapy did not result in improvements. Combination therapy had improved efficacy over naproxen monotherapy; combination therapy resulted in improved health scores, and importantly reduced mechanical and cold allodynia assessment. Furthermore, protection of articular cartilage structure and preservation of bone structure and bone volume were also observed.ConclusionsThis study demonstrates that combining KBP and naproxen may be a relevant therapeutic strategy for RA, resulting in improvements to the overall health, pain, inflammation, and joint structure.

Study of energy transfer mechanism in the EuIII and GdIII homobimetallic complexes containing the anti-inflammatory drug naproxen and N,N-donors ligands

Abstract In this work, we present the synthesis, solid state characterization and complete photoluminescence study of new important homobimetallic lanthanide complexes containing the non-steroidal anti-inflammatory drug (NSAID) naproxen. The analytical and spectroscopic techniques reveals the formation of eight compounds of general formula [Ln2(nap)6(H2O)4] (Eu 1 and Gd 2), [Ln2(nap)6(bpy)2] (Eu 3 and Gd 4), [Ln2(nap)6(4,4'-dmbpy)2] (Eu 5 and Gd 6) and [Ln2(nap)6(phen)2] (Eu 7 and Gd 8), where: nap = naproxen ligand, bpy =2,2'-bipyridine, 4,4'-dmbpy = 4,4'-dimethyl-2,2'-bipyridine and phen = 1,10-phenanthroline. Using the RM1 model, the molecular structures of the EuIII complexes were calculated, with your optimized ground state geometries used to obtain all details involved in the energy transfer process. From the respective GdIII complexes were obtained the lowest ligand triplet states, proving that the photoluminescence in the EuIII naproxen complexes is proposed to be a ligand sensitized luminescence process. On the other hand, the position of the triplet states also explains the non-effective energy transfer in the TbIII naproxen complexes. The presence of N,N-donors ligands (bpy, 4,4'-dmbpy and phen) results in an 3–4-fold increase in the quantum efficiency when compared with the EuIII complex without nitrogen ligands. The high values of emission quantum efficiency (η ~ 70 - 98%) show the EuIII complexes can be potential candidates as emitters in biologic assays.

Combined hormonal contraceptives for heavy menstrual bleeding.

Menorrhagia or heavy menstrual bleeding (HMB) is an excessive blood loss that impairs a woman's quality of life, either physical, emotional, social or material. It is benign and not associated with pregnancy or any other gynaecological or systemic disease. Medical treatments used to reduce excessive menstrual blood loss (MBL) include prostaglandin synthetase inhibitors, antifibrinolytics, oral contraceptive pills, and other hormones. The combined oral contraceptive pill (COCP) is claimed to have a variety of beneficial effects, inducing a regular shedding of a thinner endometrium and inhibiting ovulation, thus having the effect of both treating HMB and providing contraception. More recently, a contraceptive vaginal ring (CVR) has been trialled to investigate whether this treatment can provide similar benefits to COCP while lessening hormonal systemic exposure. This review is an update of a review which originally focused on COCP alone. The scope of the review has been widened to consider other types of delivery of combined hormonal contraceptives for reduction of MBL.To determine the efficacy of combined hormonal contraceptives (pills, vaginal ring or patch) compared with other medical therapies, placebo, or no therapy in the treatment of HMB. A secondary objective was to compare the COCP with the CVR.We searched the Gynecology and Fertility Group trials register, MEDLINE, Embase, CENTRAL, CINAHL and PsycINFO (search dates: Oct 1996, May 2002, June 2004, April 2006, June 2009, July 2017 and September 2018) for all randomised controlled trials (RCTs) of COCP and CVR for the treatment of HMB. We also searched trial registers and the reference lists of retrieved studies for additional trials.We included randomised controlled trials (RCTs) of the use of COCP or CVR compared with no treatment, placebo, or other medical therapies for women with HMB and regular menstrual cycles.All assessments of trial quality and data extraction were performed unblinded by at least two review authors. Our primary review outcomes were treatment success, menstrual bleeding (assessed objectively, semi-objectively or subjectively), and participant satisfaction with treatment. Secondary outcomes were adverse events, quality of life, and haemoglobin level.We identified eight RCTs involving 805 participants. Two trials comparing COCP with placebo were considered to be moderate quality and the remaining studies were low to very low quality, mainly because of serious risk of bias from lack of blinding and concerns over precision.COCP versus placeboCOCP, with a step-down oestrogen and step-up progestogen regimen, improved response to treatment (return to menstrual 'normality') (OR 22.12, 95% CI 4.40 to 111.12; 2 trials; 363 participants; I2 = 50%; moderate-quality evidence), and lowered MBL (OR 5.15, 95% CI 3.16 to 8.40; 2 trials; 339 participants; I2 = 0%; moderate-quality evidence) when compared to placebo. The results suggested that, if the chance of 'successful' treatment was 3% in women taking placebo, then COCP increased this chance from 12% to 77% in women with unacceptable HMB. Minor adverse events, in particular breast pain, were more common with COCP. No study in this comparison reported semi-objectively assessed MBL or participant satisfaction with treatment.COCP versus other medical treatmentsNon-steroidal anti-inflammatory drugs (NSAIDs)There was insufficient evidence to determine whether the COCP reduced MBL when compared to NSAIDs (mefenamic acid and naproxen). No study in this comparison reported semi-objectively assessed MBL, subjectively assessed MBL, participant satisfaction with treatment or adverse events.Levonorgestrel-releasing intrauterine system (LNG IUS)The LNG IUS was more effective than COCP in reducing MBL (OR 0.21, 95% CI 0.09 to 0.48; 2 trials; 151 participants; I2 = 0%; low-quality evidence) but it was not clear whether satisfaction with treatment or adverse effects varied according to which treatment was used. No study in this comparison reported semi-objectively assessed MBL or subjectively assessed MBL.Contraceptive vaginal ring (CVR) versus other medical treatmentsCOCP COCP was compared with CVR in two trials. There were discrepancies between some of the findings and there was no evidence of a benefit for one treatment compared to the other for response to treatment, MBL or participant satisfaction with treatment. There was a greater likelihood of nausea with COCP. No study in this comparison reported objectively assessed MBL or subjectively assessed MBL.ProgestogensCVR was compared to long course progestogens in one trial. It is possible that CVR increased the odds of satisfaction; but we are uncertain whether CVR improved MBL. The evidence was based on small numbers of participants and was very low quality, so definitive conclusions could not be reached. No study in this comparison reported objectively assessed MBL, subjectively assessed MBL, or adverse events.Moderate-quality evidence suggests that the combined oral contraceptive pill over six months reduces HMB in women with unacceptable HMB from 12% to 77% (compared to 3% in women taking placebo). When compared with other medical options for HMB, COCP was less effective than the LNG IUS. Limited evidence suggested that COCP and CVR had similar effects. There was insufficient evidence to determine comparative efficacy of combined hormonal contraceptives with NSAIDs, or long course progestogens.

A nanocomposite consisting of an amorphous seed and a molecularly imprinted covalent organic framework shell for extraction and HPLC determination of nonsteroidal anti-inflammatory drugs.

A novel nanocomposite consisting of an amorphous seed and a molecularly imprinted covalent organic framework shell was prepared via a heterogeneous nucleation and growth method. By using ibuprofen as the dummy template, a molecularly imprinted covalent organic framework (MICOF) with a large surface area was prepared from 1,3,5-triformylbenzene and 4,4'-diaminobiphenyl. It was placed on the surface of monodisperse amorphous seeds. Owing to strong π-interaction, the MICOF@SiO2 nanocomposite displays fast binding kinetics, large adsorption capacities and selectivity for nonsteroidal anti-inflammatory drugs (NSAIDs). Following desorption from the MICOF@SiO2 with methanol containing 1% ammonium hydroxide, the NSAIDs ketoprofen, ibuprofen, diclofenac, indomethacin, flurbiprofen and naproxen were quantified by HPLC with UV detection. Under optimized conditions, the method exhibits good linearity within the range of 0.002-1.0μgmL-1, low limits of detection (0.38-2.92μgL-1), and acceptable repeatability. The recoveries of NSAIDs at three spiking levels range from 77 to 112%, and the RSDs are <9.4%. The method was successfully applied to the analysis of NSAIDs in spiked environmental water samples. Graphical abstract A molecular imprinted covalent organic framework nanocomposite (MICOF@SiO2) was prepared by heterogeneous nucleation and growth method. It was explored as a sorbent for the solid phase extraction of nonsteroidal anti-inflammatory drugs before determination by HPLC with UV detection.

Synthesis, characterization and biological evaluation of naproxen Cu(II) complexes

Two Cu(II) complexes of the non-steroidal anti-inflammatory drug Naproxen were synthesized, characterized and evaluated for anti-inflammatory, analgesic, ulcerogenic and urease inhibition activities. The complex 1 [Cu(nap)2(H2O)3]·H2O was reported previously, and the crystal structure of complex 2 [Cu(nap)2(dap)(H2O)] (nap = Naproxen, dap = 1,3-diaminopropane) was confirmed by X-ray diffraction crystallography. The anti-inflammatory and ulcerogenic study showed that the compounds 1 and 2 were the promising anti-inflammatory agents and demonstrated significant gastric tolerance when compared with Naproxen, especially for complex 1 with the edema inhibition of 93.6% after 3 h, and ulcer index of 15 ± 2. Analgesic and urease inhibition assay showed that complex 2 was a potent urease inhibitor with the IC50 value of 1.69 ± 0.08 μM and pain inhibition value of 65%. As effective urease inhibitors, molecular docking study was performed to investigate the binding mode of the complexes with urease.

Infantile Cortical Hyperostosis (ICH) Secondary to Prostaglandin E1 Infusion in a Newborn with Complex Cyanotic Heart Disease: A Case Report

Infantile cortical hyperostosis (ICH), also known as Caffey’s disease, is a benign self-limiting condition affecting young infants. The initial symptom of the classical ICH is usually irritability, fever and soft tissue swelling affecting one or more bones. Diagnosis is usually delayed because its clinical presentation mimics many other clinical conditions such as osteomyelitis, scurvy, hypervitaminosis A, child abuse, bone tumor or even fracture. There are no laboratory tests to confirm the diagnosis. There are two types of ICH been described; the classical mild infantile form and the more severe prenatal form. Most of the cases of ICH are sporadic, but autosomal dominant and recessive patterns have been reported as well. It is linked with missense mutation in COL1A1, the gene encoding the α1 chain of type I collagen and has raised some doubts whether it is a type of collagen disorder, like osteogenesis imperfect. In this case, the newborn developed ICH due to prolonged infusion with prostaglandin E1 which was given in view of congenital cyanotic heart disease. Prostaglandin E1 infusion is used for maintaining the patency of ductus arteriosus in ductus dependent congenital heart defects in neonates and is usually administered before corrective heart surgery. ICH is mostly self-limiting and resolves within 12-24 months and usually does not require any treatment. Anti-inflammatory drugs such as NSAIDS(indomethacin and naproxen) and steroids has been used in symptomatic cases with success. The outcome is generally good with symptoms resolution usually before the age of one year. Relapses are uncommon.

Solubilities of Organic Semiconductors and Nonsteroidal Anti-inflammatory Drugs in Pure and Mixed Organic Solvents: Measurement and Modeling with Hansen Solubility Parameter

The solubilities of five organic semiconductors and four nonsteroidal anti-inflammatory drugs (NSAIDs) were measured by a static analytical method in a set of seven representative organic solvents at 298.15 K and 0.10 MPa to determine the Hansen solubility parameter (HSP) of the solutes by a quantitative correlation with the extended Hansen model. Solubilities of the organic semiconductors (N,N′-di-1-naphthyl-N,N′-diphenylbenzidine (NPB), 4,4′-bis(9H-carbazol-9-yl)biphenyl (CBP), anthracene, tetracene, and perylene) exhibited similar solvent dependence to each other, increasing in the order of ethanol < acetonitrile < hexane < acetone < carbon tetrachloride < chlorobenzene ≈ chloroform due to the large dispersion parameter δD ≈ 21 and the small polarity and hydrogen bonding parameters (δP, δH) ≈ (5, 5) of the solutes. In contrast, the solubilities of NSAIDs (naproxen, diclofenac, indomethacin, and niflumic acid) were hexane < carbon tetrachloride < acetonitrile ≈ chlorobenzene < ethanol ≈ chloroform < ace...

Trends and patterns of analgesic prescribing in Malaysian public hospitals from 2010 to 2016: tramadol predominately used.

PurposeTo examine the trends of analgesic prescribing at public tertiary hospital outpatient settings and explore the patterns of their utilization in nonsteroidal anti-inflammatory drugs (NSAIDs), tramadol, and opioid patients.Patients and methodsThis cross-sectional study was conducted from 2010 to 2016 using the prescription databases of two tertiary hospitals in Malaysia. Prescriptions for nine NSAIDs (ketoprofen, diclofenac, celecoxib, etoricoxib, ibuprofen, indomethacin, meloxicam, mefenamic acid, and naproxen), tramadol, and five other opioids (morphine, fentanyl, oxycodone, dihydrocodeine, and buprenorphine) were included in this study. Annual number of patients and prescriptions were measured in repeat cross-sectional estimates. Descriptive statistics and linear trend analysis were performed using Stata version 13.ResultsA total of 192,747 analgesic prescriptions of the nine NSAIDs, tramadol, and five other opioids were given for 97,227 patients (51.8% NSAIDs patients, 46.6% tramadol patients, and 1.7% opioid patients) from 2010 to 2016. Tramadol (37.9%, n=72,999) was the most frequently prescribed analgesic, followed by ketoprofen (17.5%, n=33,793), diclofenac (16.2%, n=31,180), celecoxib (12.2%, n=23,487), and other NSAIDs (<4.5%). All the analgesics were increased over time except meloxicam, indomethacin, and mefenamic acid. Opioids, primarily morphine (2.2%, n=4,021) and oxycodone (0.5%, n=1,049), were prescribed the least, but the rate of increase was the highest.ConclusionTramadol was the most frequently prescribed analgesic in hospital outpatient settings in Malaysia. Opioids were prescribed the least, but noted the highest increase in utilization.

Influence of Naproxen, Age and Body Mass Index on the Biological Composition of Leukocyte Rich Platelet-Rich Plasma: A Prospective, Therapeutic, Cohort Study

Objectives:Platelet-rich plasma (PRP) is comprised of several biologically active factors that can stimulate musculoskeletal healing processes. Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat many musculoskeletal conditions and influence platelet function. The influence of NSAIDs on the biological composition of PRP is not well known. The purpose of this study was to quantify and compare growth factors and other chemokines and cytokines in leukocyte-rich PRP (LR-PRP) between baseline, following one-week of NSAID (Naproxen) use, and after a one-week washout period. We hypothesized that Naproxen would alter both the catabolic and anabolic factors in LR-PRP. Our secondary hypothesis was that discontinuing Naproxen use for one-week would be sufficient to return LR-PRP’s molecular constituents back to baseline.Study Design:Non-randomized, prospective cohort study; Level of evidence: 2.Methods:Sixteen healthy volunteers (n=8 male and n=8 females) were enrolled in this IRB approved study. Peripheral blood was drawn at three-time points: baseline, one-week after Naproxen intake, and after a one-week washout period. Donors were instructed after the first blood-draw to ingest oral Naproxen tablets twice a day (440 mg bid) for one-week. Fifty-two anabolic and catabolic factors in LR-PRP were measured at all time points. Donor demographics were collected at the time of the initial blood-draw. To address the primary hypothesis of this study, Friedman’s test was used to identify significant differences between the baseline, Naproxen and washout time points while accounting for the repeated measures design of this study. When Friedman’s test was significant, pairwise comparisons were made using Holm’s method to control the family-wise type 1 error rate.Results:Three anabolic growth factors, platelet derived growth factor-AA (PDGF-AA, Figure 1), platelet derived growth factor-AB (PDGF-AB, Figure 1), and transforming growth factor-β1 (TGF-β1), had a significant decline from baseline (p<0.05) after one-week of Naproxen use. There was a significant recovery (p<0.05) of PDGF-AA and PDGF-AB levels after the one-week washout of NSAIDs, with a return to baseline levels. TGF-β1 did not recover to baseline levels after a one-week washout period. Catabolic factors tumor necrosis factor-β (TNF-β) and interleukin-6 (IL-6) had a significant decline from baseline (p<0.05) after NSAID use for one-week and returned to levels similar to baseline (p<0.05) after a one-week washout period.Conclusion:Naproxen use diminished several biological factors in LR-PRP; however, a one-week washout period was sufficient for the recovery of PDGF-AA, PDGF-AB, TNF-β, and IL-6 to return to baseline levels. Our results suggest that patients undergoing PRP treatment should discontinue Naproxen, and other NSAID use, at least one-week prior to harvest and injection of PRP.

Separation and purification of intermediates for the preparation of naproxen from synthetic mixtures by countercurrent chromatography.

Three key intermediates in the preparation of the nonsteroidal anti-inflammatory drug naproxen were successfully separated and purified with high purity from synthetic mixtures by countercurrent chromatography with a selected biphasic solvent system. The biphasic solvent system composed of n-hexane/ethyl acetate/methanol/water (9:1:9:1, v/v/v/v) was selected according to partition performance of the three components using thin-layer chromatography. Fifty milligrams of the synthetic mixture after the three-step reaction was injected into a preparative countercurrent chromatography separation column and yielded 3.5, 14.0, and 8.0mg of three key intermediates with 95.0, 99.0, and 98.0% purity, and the recovery of each component was 65.2, 71.2, and 69.6%, respectively. The results indicated that countercurrent chromatography is an efficient alternative and economical method for the separation and purification of intermediate components from synthetic mixtures.

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs.

Efficacy of naproxen prophylaxis for the prevention of heterotopic ossification after hip surgery: a meta-analysis

BackgroundThis meta-analysis aimed to assess whether the specific nonsteroidal anti-inflammatory drug (NSAID) naproxen has a role in reducing the occurrence of heterotopic ossification after hip surgery.MethodsPotential studies were identified in the following electronic databases: PubMed, EMBASE, Web of Science, Cochrane Library, and Google. We included studies involving hip surgery patients in which the intervention group received naproxen and the control group received placebo. The occurrence of heterotopic ossification and complications were the final outcomes. Stata 13.0 was used for the meta-analysis.ResultsFour randomized controlled trials (RCTs) involving 269 patients were ultimately included in this meta-analysis. The use of naproxen was associated with a significant reduction in the occurrence of heterotopic ossification at 1.5-, 3-, 6-, and 12-month follow-ups (P < 0.05). There was no significant difference in the occurrence of complications between treatment and control groups (P > 0.05).ConclusionOur analysis indicates that naproxen can decrease the occurrence of heterotopic ossification without increasing complications in hip surgery patients. Due to the limited number of studies included, more high-quality RCTs are needed to identify the optimal dose of naproxen.

Pharmacological characterisation of CR6086, a potent prostaglandin E2 receptor 4 antagonist, as a new potential disease-modifying anti-rheumatic drug

BackgroundProstaglandin E2 (PGE2) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play a key role in the onset and progression of rheumatoid arthritis (RA). We present the pharmacological characterisation of CR6086, a novel EP4 receptor antagonist, and provide evidence for its potential as a disease-modifying anti-rheumatic drug (DMARD).MethodsCR6086 affinity and pharmacodynamics were studied in EP4-expressing HEK293 cells by radioligand binding and cyclic adenosine monophosphate (cAMP) production, respectively. In immune cells, IL-6 and vascular endothelial growth factor (VEGF) expression were analysed by RT-PCR, and IL-23 and IL-17 release were measured by enzyme-linked immunosorbent assay (ELISA). In collagen-induced arthritis (CIA) models, rats or mice were immunised with bovine collagen type II. Drugs were administered orally (etanercept and methotrexate intraperitoneally) starting at disease onset. Arthritis progression was evaluated by oedema, clinical score and histopathology. Anti-collagen II immunoglobulin G antibodies were measured by ELISA.ResultsCR6086 showed selectivity and high affinity for the human EP4 receptor (Ki = 16.6 nM) and functioned as a pure antagonist (half-maximal inhibitory concentration, 22 nM) on PGE2-stimulated cAMP production. In models of human immune cells in culture, CR6086 reduced key cytokine players of RA (IL-6 and VEGF expression in macrophages, IL-23 release from dendritic cells, IL-17 release from Th17 cells). In the CIA model of RA in rats and mice, CR6086 significantly improved all features of arthritis: severity, histology, inflammation and pain. In rats, CR6086 was better than the selective cyclooxygenase-2 inhibitor rofecoxib and at least as effective as the Janus kinase inhibitor tofacitinib. In mice, CR6086 and the biologic DMARD etanercept were highly effective, whereas the non-steroidal anti-inflammatory drug naproxen was ineffective. Importantly, in a study of CR6086/methotrexate, combined treatment greatly improved the effect of a fully immunosuppressive dose of methotrexate.ConclusionsCR6086 is a novel, potent EP4 antagonist showing favourable immunomodulatory properties, striking DMARD effects in rodents, and anti-inflammatory activity targeted to immune-mediated inflammatory diseases and distinct from the general effects of cyclooxygenase inhibitors. These results support the clinical development of CR6086, both as a stand-alone DMARD and as a combination therapy with methotrexate. The proof-of-concept trial in patients with RA is ongoing.

Degradation of anti-inflammatory drugs in municipal wastewater by heterogeneous photocatalysis and electro-Fenton process

ABSTRACTNon-steroidal anti-inflammatory drugs (NSAID) are compounds frequently found in municipal wastewater and their degradation by conventional wastewater treatment plants (WWTP) is generally incomplete. This study compared the efficiency of two advanced oxidation processes (AOP), namely heterogeneous photocatalysis (HP) and electro-Fenton (EF), in the degradation of a mixture of common NSAID (diclofenac, ibuprofen and naproxen) dissolved in either deionized water or effluent from a WWTP. Both processes were effective in degrading the NSAID mixture and the trend of degradation was as follows, diclofenac > naproxen > ibuprofen. EF with a current density of 40 mA cm−2 and 0.3 mmol Fe2+ L−1 was the most efficient process to mineralize the organic compounds, achieving up to 92% TOC removal in deionized water and 90% in the WWTP effluent after 3 h of reaction. HP with 1.4 g TiO2 L−1 at pH 7 under sunlight, produced 85% TOC removal in deionized water and 39% in WWTP effluent also after 3 h treatment. The lower TOC removal efficiency shown by HP with the WWTP effluent was attributed mainly to the scavenging of reactive species by background organic matter in the wastewater. On the contrary, inorganic ions in the wastewater may produce oxidazing species during the EF process, which contributes to a higher degradation efficiency. EF is a promising option for the treatment of anti-inflammatory pharmaceuticals in municipal WWTP at competitive electrical energy efficiencies.

Manganese(ii) complexes with the non-steroidal anti-inflammatory drugs naproxen and mefenamic acid: synthesis, structure, antioxidant capacity, and interaction with albumins and DNA

The structure, antioxidant activity and interaction with DNA and albumins of a series of manganese(ii) complexes of mefenamic acid or naproxen are presented herein.

Photo-switchable nanoporous silica supports for controlled drug delivery

A stimuli-responsive drug delivery system consisting of SBA-12 nanoporous silica modified with a photo-switchable coumarin ligand was studied for the delivery of the non-steroidal anti-inflammatory drug naproxen.

Correlation between glucuronidation and covalent adducts formation with proteins of nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause idiosyncratic liver injury. Mechanisms involved in NSAID-induced liver injury are complex. Previous studies have suggested that acyl glucuronide of NSAIDs (NSAIDs-Glu) plays an important role in the development of liver injury via covalently binds to proteins and the resultant adduct induces immunological toxicity. As only some NSAIDs-Glu are commercially available, the evaluation of covalent protein adduct formation using ready-made NSAIDs-Glu is difficult and inconvenient. Moreover, glucuronidation potency varies with the NSAID, including stereoisomers. Therefore, in this study, we simultaneously examined the glucuronidation and covalent adduct formation using enantiomers of parent NSAIDs (ibuprofen, naproxen, pranoprofen, ketoprofen, and flurbiprofen) in rat liver microsomes. Glucuronides and covalent adducts were quantified by HPLC. The amount of covalent adduct increased with NSAIDs-Glu formation in the rat liver microsomes in a time-dependent manner. A significant positive correlation was observed between the AUC of NSAIDs-Glu and that of covalent adduct, except ketoprofen. Although ketoprofen exhibited the highest glucuronidation rate among the NSAIDs investigated, the amount of covalent adduct was similar to that for pranoprofen, which had the lowest glucuronidation rate. Thus, it may be difficult for ketoprofen glucuronide to covalently bind with proteins in the rat liver microsomes. Our results suggested that the amount of glucuronide formed is a key factor in predicting covalent bond formation with protein in NSAIDs, in addition to degradability and bindability with proteins of NSAIDs-Glu. Further studies are required to confirm the relationship between the tendency of glucuronidation and the formation of covalent adducts of NSAIDs.

Multifunctionalized mesoporous silica as an efficient reversed-phase/anion exchange mixed-mode sorbent for solid-phase extraction of four acidic nonsteroidal anti-inflammatory drugs in environmental water samples

A mesoporous silica Santa Barbara Amorphous-15 (SBA-15) has been first functionalized with 3-[2-(2-aminoethylamino)ethylamino]propyl-trimethoxysilane (a silane with three amines) and then reacted with an excess of phenyl glycidyl ether to generate a mixed-mode anion-exchanger containing both anion-exchange (three amines) and reversed-phase (multiple ether-linked phenyls) functionalities in a single branched ligand. The resulting material has been characterized by scanning electron microscopy, transmission electron microscopy, nitrogen adsorption-desorption measurements, Fourier-transform infrared spectroscopy, and elemental analysis. The results obtained indicated a BET specific surface area (SBET) of 362.5m2g−1, a pore volume of 0.70cm3g−1 with a narrow pore size distribution centered at 6.6nm, and carbon and nitrogen contents of 28.30% and 2.84%, respectively. The dimensions of these particles (∼5μm diameter, ∼60μm length), their large surface areas, their high-density functionalities and anion-exchange mixed-mode characteristics make them very attractive for highly effective solid phase extraction (SPE) of acidic nonsteroidal anti-inflammatory drugs (NSAIDs). The important parameters on extraction efficiency including sample pH, breakthrough volume, type and volume of eluent were optimized. A simple and sensitive analytical method based on mixed-mode SPE coupled to high-performance liquid chromatography with ultraviolet detection (HPLC-UV) was developed and successfully applied to the analysis of four NSAIDs (ketoprofen, naproxen, diclofenac, and ibuprofen) in spiked real water samples with satisfactory recoveries (80.6–110.9%) and repeatability (relative standard deviation <11.3%, n=3). The limit of detections of four NSAIDs were 0.006–0.070μgL−1 for tap water, and 0.014–0.16μgL−1 for river water and wastewater, with the enrichment factors of 806–1109-fold.

Pharmaceuticals and other anthropogenic chemicals in atmospheric particulates and precipitation

Air and precipitation samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC–MS) for pharmaceuticals, personal care products, and other commercial chemicals within the St. Paul/Minneapolis metropolitan area of Minnesota, U.S. Of the 126 chemicals analyzed, 17 were detected at least once. Bisphenol A, N,N-diethyl-meta-toluamide (DEET), and cocaine were the most frequently detected; their maximum concentrations in snow were 3.80, 9.49, and 0.171ng/L and in air were 0.137, 0.370, and 0.033ng/m3, respectively. DEET and cocaine were present in samples of rain up to 14.5 and 0.806ng/L, respectively. Four antibiotics - ofloxacin, ciprofloxacin, enrofloxacin, and sulfamethoxazole - were detected at concentrations up to 10.3ng/L in precipitation, while ofloxacin was the sole antibiotic detected in air at 0.013ng/m3. The X-ray contrast agent iopamidol and the non-steroidal anti-inflammatory drug naproxen were detected in snow up to 228ng/L and 3.74ng/L, respectively, while caffeine was detected only in air at 0.069 and 0.111ng/m3. Benzothiazole was present in rain up to 70ng/L, while derivatives of benzotriazole – 4-methylbenzotriazole, 5-methylbenzotriazole, and 5-chlorobenzotriazole - were detected at concentrations up to 1.5ng/L in rain and 3.4ng/L in snow. Nonylphenol and nonylphenol monoethoxylate were detected once in air at 0.165 and 0.032ng/m3, respectively. Although the sources of these chemicals to atmosphere are not known, fugacity analysis suggests that wastewater may be a source of nonylphenol, nonylphenol monoethoxylate, DEET, and caffeine to atmosphere. The land-spreading of biosolids is known to generate PM10 that could also account for the presence of these contaminants in air. Micro-pollutant detections in air and precipitation are similar to the profile of contaminants reported previously for surface water. This proof of concept study suggests that atmospheric transport of these chemicals may partially explain the ubiquity of these contaminants in the aquatic environment.

Preemptive Use of Naproxen on Tooth Sensitivity Caused by In-Office Bleaching: A Triple-Blind, Crossover, Randomized Clinical Trial.

A triple-blind, randomized, crossover clinical trial evaluated prior use of nonsteroidal anti-inflammatory naproxen on sensitivity reported by patients undergoing in-office tooth bleaching. Fifty patients were subjected to two sessions of in-office tooth bleaching with 35% hydrogen peroxide in a single application of 40 minutes for two sessions, with an interval of seven days between applications. One hour prior to the procedure, each patient randomly received a single dose of naproxen (500 mg) or placebo. The patient's sensitivity level was evaluated during and immediately after the bleaching using two scales (verbal and visual analog); the verbal scale only was repeated after 24 hours. The effectiveness of the bleaching procedures was evaluated with the Bleachedguide scale. Relative risk to sensitivity was calculated and adjusted by session, while comparison of overall risk was performed by the McNemar test. Data on the sensitivity level for both scales and shade were subjected to the Friedman, Wilcoxon, and Mann-Whitney tests (α=0.05). The use of naproxen only decreased the absolute risk and intensity of tooth sensitivity reported immediately after the second session. On the other hand, no measurable effect was observed during or 24 hours after either session. The sequence of drug administration did not affect the bleaching effectiveness. Preemptive use of naproxen only reduced tooth sensitivity reported by patients immediately after the second session of bleaching.