Non-steroidal Anti-inflammatory Drugs Naproxen Research Articles

Design of 3D multi-layered electrospun membranes embedding iron-based layered double hydroxide for drug storage and control of sustained release

Nowadays polymer dressings are expected to possess multiply functions. Besides acting as physical barriers, dressings may provide for the injured tissue species able to turn wound healing process faster and painless. In this way, dressings can be designed aiming to enable the release of drugs. The possibility to modulate drug release kinetics is a desired characteristic to be achieved in order to turn drug delivery systems adequate to specific treatments. However, hydrophilic drugs and hydrophobic polymers incompatibility hinders such modulation and a long-term release cannot be achieved efficiently. Here we present the design of poly(lactic acid) (PLA) membranes containing iron-based Layered Double Hydroxide (LDH) particles able to storage a hydrophilic anionic drug (derived from the non-steroidal anti-inflammatory naproxen). LDH particles are excellent candidates to compose multifunctional composites. They may present diverse biocompatible compositions, possess an elevated encapsulation capacity and tends to promote drugs sustained release by its own, besides assisting tissues regeneration process. Nanofibrous membranes were prepared by the combination of electrospun PLA and electrosprayed LDH as alternated layers (approach A) and also by both technics performed at the same time (approach B). In approach A, by varying the thickness of the PLA fibrous layers, it was possible to easily modulate the drug release rate. Half of drug content was released after 1, 4 and 17 days for the membranes containing the thinnest, the intermediate and the thicker PLA layers, respectively, and after 56 h for the membrane prepared by the approach B. Naproxen release was kept for 18 days for the thinnest membrane, 59 days for the membrane prepared by the approach B and 66 days for the thicker membranes. We believe that this work can inspire the development of new functional membranes with tunable drug release profile thanks to the versatile electrospinning and electrospraying techniques.

Metabolic Capability of Penicillium oxalicum to Transform High Concentrations of Anti-Inflammatory and Analgesic Drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics are two of the most employed drug groups around the world due to their use in the treatment of edema and pain. However, they also present an ecological challenge because they are considered as potential water pollutants. In this work, the biodegradation of four NSAIDs (diclofenac, ibuprofen, naproxen and ketoprofen) and one analgesic (acetaminophen) at 50 µM (initial concentration) by Penicillium oxalicum, at both flask and bioreactor bench scales, was evaluated. An important co-metabolic mechanism as part of the global bioremediation process for the elimination of these drugs was observed, as in some cases it was necessary to supplement glucose to achieve a 100% removal rate: both individually and as a complex mixture. Identical behavior in the implementation of a fluidized bench-scale batch bioreactor, inoculated with pellets of this fungus and the complex mix of the drugs, was observed. The role of the cytochrome P450 enzymes (CYP) in the biodegradation of the drugs mix were evidenced by the observation of hydroxylated by-products. The results on the reduction of toxicity (micro and phyto) were not conclusive; however, a reduction in phytotoxicity was detected.

Activated carbon embedded alginate beads for removing nonsteroidal anti-inflammatory drug naproxen from wastewater: equilibrium, kinetics, thermodynamics, desorption, and reusability.

In the present study, activated carbon/alginate (AC/ALG) beads were successfully synthesized with different AC:ALG ratios of 1.0-3.0 (w/v) and used for the adsorption of the nonsteroidal anti-inflammatory drug naproxen from wastewater. The beads were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and Brunauer-Emmett-Teller (BET) analysis, and adsorbent dosage, initial pH, initial naproxen concentration, and contact time in removal efficiency were investigated. Maximum naproxen removal percentage was achieved using 350 mg of AC/ALG beads with a ratio of 3.0% (w/v) within six hours and naproxen removal performance was determined to be 98.0%. Freundlich, Temkin, and Dubinin-Radushkevich (D-R) isotherm models were fitted to the equilibrium data better than the Langmuir model. According to kinetics results, the equilibrium time for the AC/ALG beads was reached in four hours and the kinetic model was determined by the pseudo-second-order equation. The thermodynamic parameters were calculated and enthalpy of naproxen adsorption was found to be positive for all AC/ALG beads. After the adsorption process the beads can easily be regenerated by ethanol and reused within seven cycles.

Simultaneous Determination of Four Nonsteroidal Anti-Inflammatory Drugs and Three Estrogen Steroid Hormones in Wastewater Samples by Dispersive Liquid-Liquid Microextraction Based on Solidification of Floating Organic Droplet and HPLC.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and estrogen steroid hormones (estrogens) are pharmaceuticals intensively studied in environmental analysis due to their toxic effect on animal and human beings. Development of a simple, fast, and sensitive extraction method for the simultaneously analysis of four NSAIDs (ketoprofen, naproxen, ibuprofen, and diclofenac) and three estrogens (17ß-estradiol, 17α-ethynylestradiol, and estriol) from wastewater samples. Dispersive liquid-liquid microextraction based on solidification of floating organic droplet followed by HPLC analysis with UV detection was developed. The influence of the main extraction parameters, e.g., the volume of extraction solvent and of disperser, the pH, and the ionic strength of sample were evaluated. Good resolutions between the selected drugs were obtained using a reverse-phase column and a mobile phase of acetonitrile and water. This method provides good linearity (r > 0.999) in a concentration range of 1-100 µg/mL, good intra- and inter-day precision (RSD <7%) and low LOQs. The obtained enrichment factors were ranged between 162 and 180 for NSAIDs and between 118 and 185 for estrogens. The relative recoveries were situated >80% for all analysed drugs, except estriol (59%) both in synthetic and real wastewater samples. The developed method has been successfully applied for the analysis of the selected drugs in wastewater samples collected from the influent of a wastewater treatment plant. Four NSAIDs and three estrogens from wastewater samples were simultaneously extracted and analysed using only 10 mL of sample and 50 μL of extraction solvent.

Investigating the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the composition and ultrastructure of green leafy vegetables with important nutritional values

The global presence of pharmaceuticals in the environment has been particularly considered a concerning problem with unknown consequences. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed drugs in the world, and as a result, they are commonly found in different environmental compartments. In the present work, we studied the effects of NSAIDs (diclofenac, ibuprofen, and naproxen) on the composition and ultrastructure of Atriplex patula L., S. oleracea, and Lactuca sativa L., three green leafy vegetables with significant nutritional value. Contaminant solutions of NSAIDs were applied every two days using concentrations of 0.1 mg L−1, 0.5 mg L−1, and 1 mg L−1. After eight weeks of exposure of the green leafy vegetables to the selected NSAIDs, the chlorophylls (a + b), carotenoids (zeaxanthin, lutein, and ß-carotene), total polyphenol and total flavonoid contents, antioxidant capacity, and the ultrastructural modifications were determined. The obtained results indicated a moderate reduction in the assimilating pigments, total polyphenol and flavonoid contents. In addition, ultrastructural damages of the chloroplasts and cell walls were observed in the leaves of the selected vegetables, which were exposed to abiotic stress-induced by NSAIDs. All data collectively suggest that this group of drugs induced harmful effects on plants, and implicitly they may also negatively affected human health on the long term.

Combination of Erlotinib and Naproxen Employing Pulsatile or Intermittent Dosing Profoundly Inhibits Urinary Bladder Cancers.

Daily dosing of either NSAIDs or EGFR inhibitors has been shown to prevent bladder cancer development in a N-butyl-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced rat model. However, these inhibitors cause gastrointestinal ulceration and acneiform rash, respectively, limiting their continuous use in a clinical prevention setting. We studied chemopreventive efficacy of pulsatile dosing of EGFR inhibitor erlotinib (42 mg/kg BW, once/week) combined with intermittent or continuous low doses of the NSAID naproxen (30 mg/kg BW/day, 3 weeks on/off or 128 ppm daily in diet) in the OH-BBN induced rat bladder cancer model. The interventions were started either at 1 or 4 weeks (early intervention) or 3 months (delayed intervention) after the last OH-BBN treatment, by which time the rats had developed microscopic bladder lesions. All combination regimens tested as early versus late intervention led to the reduction of the average bladder tumor weights (54%-82%; P < 0.01 to P < 0.0001), a decrease in tumor multiplicity (65%-85%; P < 0.01 to P < 0.0001), and a decrease in the number of rats with large palpable tumors (>200 mg; 83%-90%; P < 0.01 to P < 0.0001). Levels of signal transduction markers, Ki-67, cyclin D1, IL1β, pSTAT3, and pERK, were significantly (P < 0.05 to P < 0.001) reduced in the treated tumors, demonstrating their potential utility as predictive markers for efficacy. These findings demonstrate that significant chemopreventive efficacy could be achieved with alternative intervention regimens designed to reduce the toxicity of agents, and that starting erlotinib and/or naproxen treatments at the time microscopic tumors were present still conferred the efficacy.

Thermal behavior of naproxen and ketoprofen nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs naproxen (NAP) ((+)-(S)-2-(6-methoxynaphthalen-2-yl) propionic acid) and ketoprofen (KET) (RS)-(2-(3-benzoylphenyl)-propionic acid) were investigated by thermoanalytical techniques (TG/DTG/DTA, DSC and hot-stage microscopy) and evolved gas analysis (TG-FTIR) for evaluating their thermal behavior. In air, TG curve of NAP presented one mass loss step followed by the burning of carbonaceous material, with final residue of 1.5%, while in nitrogen, a single mass loss step was observed. After melting, if the sample is submitted to an isotherm it evaporates. According to DSC curve, NAP melts at 153.5 °C (∆Hfus = 31.6 kJ mol−1; ∆Sfus = 73.5 J K−1 mol−1) and recrystallizes in the cooling step. These events were confirmed by hot-stage microscopy. TG-FTIR studies revealed that NAP decomposes by releasing 2-methoxynaphthalene and propionic acid. Ketoprofen TG curves in both atmospheres presented a single mass loss. When the sample was kept under isotherm, after melting, it evaporated. From DSC data, the melting at 93.3 °C (∆Hfus=28.4 kJ mol−1, ∆Sfus = 76.9 J K−1 mol−1) was observed, without crystallization or cooling.

Distribution and Removal of Pharmaceuticals in Liquid and Solid Phases in the Unit Processes of Sewage Treatment Plants.

In this study, we analyzed 27 pharmaceuticals in liquid and solid phase samples collected from the unit processes of four different sewage treatment plants (STPs) to evaluate their distribution and behavior of the pharmaceuticals. The examination of the relative distributions of various categories of pharmaceuticals in the influent showed that non-steroidal anti-inflammatory drugs (NSAIDs) were the most dominant. While the relative distribution of antibiotics in the influent was not high (i.e., 3%–5%), it increased to 14%–30% in the effluent. In the four STPs, the mass load of the target pharmaceuticals was reduced by 88%–95% mainly in the biological treatment process, whereas the ratio of pharmaceuticals in waste sludge to those in the influent (w/w) was only 2%. In all the STPs, the removal efficiencies for the stimulant caffeine, NSAIDs (acetaminophen, naproxen, and acetylsalicylic acid), and the antibiotic cefradine were high; they were removed mainly by biological processes. Certain compounds, such as the NSAID ketoprofen, contrast agent iopromide, lipid regulator gemfibrozil, and antibiotic sulfamethoxazole, showed varying removal efficiencies depending on the contribution of biodegradation and sludge sorption. In addition, a quantitative meta-analysis was performed to compare the pharmaceutical removal efficiencies of the biological treatment processes in the four STPs, which were a membrane bioreactor (MBR) process, sequencing batch reactor (SBR) process, anaerobic–anoxic–oxic (A2O) process, and moving-bed biofilm reactor (MBBR) process. Among the biological processes, the removal efficiency was in the order of MBR > SBR > A2O > MBBR. Among the tertiary treatment processes investigated, powdered activated carbon showed the highest removal efficiency of 18%–63% for gemfibrozil, ibuprofen, ketoprofen, atenolol, cimetidine, and trimethoprim.

Prescribing of Nonsteroidal Anti-inflammatory Drugs, Tramadol, and Opioids in Children: Patterns of Its Utilization.

ABSTRACTBackground:Analgesic is commonly used in children but little is known about its patterns of utilization. This study explored the patterns of analgesic prescribing in children.Materials and Methods:This cross-sectional study used prescription databases of tertiary hospital settings in Malaysia from 2010 to 2016. Prescriptions for nine NSAIDs (diclofenac, ketoprofen, etoricoxib, celecoxib, ibuprofen, indomethacin, mefenamic acid, meloxicam, and naproxen), tramadol, and five other opioids (morphine, oxycodone, fentanyl, buprenorphine, and dihydrocodeine) prescribed for children aged <18 years were included. Number of annual patients and prescriptions were measured and analyzed using Stata v15.Results:During a 7-year study period, a total of 5040 analgesic prescriptions of the nine NSAIDs, tramadol, and five other opioids were prescribed for 2460 pediatric patients (81.8% NSAIDs patients, 17.9% tramadol patients, and 0.3% opioid patients). Ibuprofen was the primary analgesic in young children less than 12 years old (≤2 years old [y.o.] [75%], 3–5 y.o. [85%], and 6–12 y.o. [56.3%]). However, there was a wide range of analgesics used in older children (>12 y.o.) with the majority for naproxen (13–15 y.o. (28.2%) and 16–17 y.o. (28.2%). Other frequently prescribed analgesics for older children included ibuprofen (20.6%) and diclofenac (18.2%) for 12–15 y.o. and diclofenac (26.7%) and tramadol (17.6%) for 16–17 y.o.Conclusion:Ibuprofen was the primary analgesic for children less than 12 y.o., whereas there was a wide range of analgesics prescribed for children age >12 y.o. including naproxen, diclofenac, and tramadol.

Methotrexate in Early Chikungunya Arthritis: A 6 Month Randomized Controlled Open-label Trial.

Evidence for treating chikungunya arthritis early in the course of illness is scarce. This study assesses the efficacy of Methotrexate in early Chikungunya arthritis. It is a randomized controlled open-label assessor-blinded trial with a crossover design. Sixty patients with persistent post chikungunya arthritis with at least 3 or more tender or swollen joints (28 joint count) were recruited. MTX arm was given oral Methotrexate and NSAID arm was given NSAIDs (Naproxen 1 gm/day or Etoricoxib 120 mg/day). Patients were followed at 1, 2, 4 and 6 months. After 2 months patients in NSAID arm who have not achieved remission were given MTX. The primary endpoint was remission (no tender or swollen joints by 28 joint count) at 6 months. Secondary endpoints were change in CDAI, Indian HAQ, total steroid use, total NSAID use, and serious adverse effects. Intention to treat analysis was used. TJC, SJC, CDAI and HAQ were matched between two at baseline. Remission was achieved by 28 patients (93%, CI- 78%-98%) in the NSAID arm and 26 patients (86%, CI-70%- 94%) in MTX arm (p=0.18). There was no significant difference in steroid need, change in HAQ, CDAI, TJC or SJC. Those who have not achieved remission had higher disease activity at baseline. A protocol-based approach with steroid and NSAIDs helped to achieve remission in most patients with early subacute phase of post-Chikungunya arthritis and the effect was comparable to that of early initiation of methotrexate.

Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding.

Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels, which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea. To determine the effectiveness, safety and tolerability of NSAIDs in achieving a reduction in menstrual blood loss (MBL) in women of reproductive years with HMB. We searched, in April 2019, the Cochrane Gynaecology and Fertility specialised register, Cochrane Central Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, the clinical trial registries and reference lists of articles. The inclusion criteria were randomised comparisons of individual NSAIDs or combined with other medical therapy with each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment-induced) causes for their HMB. We identified 19 randomised controlled trials (RCTs) (759 women) that fulfilled the inclusion criteria for this review and two review authors independently extracted data. We estimated odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes from the data of nine trials. We described in data tables the results of the remaining seven cross-over trials with data unsuitable for pooling, one trial with skewed data, and one trial with missing variances. One trial had no data available for analysis. As a group, NSAIDs were more effective than placebo at reducing HMB but less effective than tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs, but this did not appear to affect the acceptability of treatment, based on trials from 1980 to 1990. However, currently danazol is not a usual or recommended treatment for HMB. There was no clear evidence of difference between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system and the oral contraceptive pill (OCP), but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. The evidence quality ranged from low to moderate, the main limitations being risk of bias and imprecision. NSAIDs reduce HMB when compared with placebo, but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, there was no clear evidence of a difference in efficacy between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCP or the older progesterone-releasing intrauterine system.

Differential chemoreactome analysis of synergistic combinations of tolperisone and nonsteroidal anti-inflammatory drugs

The concurrent use of muscle relaxants and nonsteroidal anti-inflammatory drugs (NSAIDs) is a promising treatment for painful muscle hypertonia and convulsive states.Objective: to identify the most effective and safe synergist combinations of tolperisone and NSAIDs.Material and methods. A differential chemoreactome analysis was employed to evaluate the effects of the muscle relaxant tolperisone and five NSAIDs (dexketoprofen, etoricoxib, meloxicam, naproxen, and diclofenac). The biological activities of the molecules under study were assessed in five sections: 1) inhibition of the proteins of prostaglandin and leukotriene metabolism; 2) inhibition of the effects of the transcription factor nuclear factor kappa, tumor necrosis factor-, and other anti-inflammatory mechanisms; 3) inhibition of excessive blood coagulation and platelet aggregation; 4) vasodynamic effects; 5) antitumor properties on cell lines in culture.Results and discussion. Based on the differences in the pharmacological activity profiles of tolperisone and NSAIDs under study, the investigators identified the most promising synergistic combinations, in which both active ingredients complemented each other as effectively and safely as possible. The obtained estimates of the degree of synergism of various combinations of tolperisone and NSAIDs hold that the most promising antithrombotic, and antitumor effects.Conclusion. The results of this study will help adequately choose combinations of muscle relaxants and NSAIDs in patients with muscle hypertonia, which will be able to improve the efficiency and safety of treatment.

Evaluation of the photosynthetic parameters, emission of volatile organic compounds and ultrastructure of common green leafy vegetables after exposure to non-steroidal anti-inflammatory drugs (NSAIDs).

Understanding the effects of many essential non-steroidal anti-inflammatory drugs (NSAIDs) on plants is still limited, especially at environmentally realistic concentrations. This paper presents the influence of three of the most frequently used NSAIDs (diclofenac, ibuprofen, and naproxen) at environmentally realistic concentrations on the autochthonous green leafy vegetables: orache (Atriplex patula L.), spinach (Spinacia oleracea L.) and lettuce (Lactuca sativa L.). Our research was focused on the determination of the photosynthetic parameters, the emission rate of volatile organic compounds, and the evaluation of the ultrastructure of leaves of studied vegetables after exposure to abiotic stress induced by environmental pollutants, namely NSAIDs. The data obtained indicate a moderate reduction of foliage physiological activity as a response to the stress induced by NSAIDs to the selected green leafy vegetables. The increase of the 3-hexenal and monoterpene emission rates with increasing NSAIDs concentration could be used as a sensitive and a rapid indicator to assess the toxicity of the NSAIDs. Microscopic analysis showed that the green leafy vegetables were affected by the selected NSAIDs. In comparison to the controls, the green leafy vegetables treated with NSAIDs presented irregular growth of glandular trichomes on the surface of the adaxial side of the leaves, less stomata, cells with less cytoplasm, irregular cell walls and randomly distributed chloroplasts. Of the three NSAIDs investigated in this study, ibuprofen presented the highest influence. The results obtained in this study can be used to better estimate the impact of drugs on the environment and to improve awareness on the importance of the responsible use of drugs.

Long-term exposure to the non-steroidal anti-inflammatory drug (NSAID) naproxen causes thyroid disruption in zebrafish at environmentally relevant concentrations

The presence of trace levels of pharmaceuticals is an emerging issue impacting the aquatic ecosystem. Naproxen (NPX) is a nonsteroidal anti-inflammatory drug (NSAID) that has been frequently detected in aquatic environments worldwide. Recently, concerns regarding endocrine disruption by NSAIDs have increased; however, their effects on the thyroid system have yet to be understood. In this study, zebrafish were utilized to evaluate the thyroid-disrupting effects of NPX. After a 60-day exposure to various concentrations of NPX (0.1, 1, 10 and 100 μg/L), the body length and weight of the zebrafish were significantly decreased. The decrease of cytochrome P450 gene expression and enzyme activity might inhibit the metabolism of NPX, which might result in the significant bioconcentration in zebrafish. Thyroid hormone (TH) analysis showed that both triiodothyronine (T3) and thyroxine (T4) levels were substantially decreased. Gene transcription expressions along the hypothalamic-pituitary-thyroid (HPT) axis were also markedly affected. Significant downregulation of dio1, dio2, nis, nkx2.1, pax8, tg, tpo, trβ and ttr levels, along with the stimulation of the tshβ gene, were also observed in exposed fish compared to controls. Western blot analysis indicated that expression of the TTR protein was significantly decreased, which coincides with the results of the gene expression analysis. Collectively, our observations show that NPX increases the risk of bioconcentration and thyroid disruption in zebrafish. Given the continued increasing consumption and emission of pharmaceuticals, thyroid disruption should be considered when assessing the aquatic risk of long-term exposure to environmentally relevant concentrations of pharmaceuticals.

Cytotoxic ruthenium(II) polypyridyl complexes with naproxen as NSAID: Synthesis, biological interactions and antioxidant activity

The non-steroidal anti-inflammatory drug (NSAID) naproxen (nap) bound to ruthenium(II) in the presence of a bidentate nitrogen donor heterocyclic ligands (bpy = 2,2′-bipyridine and phen = 1,10-phenanthroline), namely, [Ru(bpy)2(nap)][PF6] (1) and [Ru(phen)2(nap)][PF6] (2) have been synthesized and characterized using various physicochemical methods. Naproxen was coordinated to the Ru(II) center through carboxylato oxygen atoms (–COO−) in a bidentate fashion. The compounds were evaluated for their photophysical properties, stability in solution, reactivity with 5′-guanosine monophosphate (5′-GMP) and GSH, interactions with CT-DNA and BSA. The complexes showed high binding affinity or reactivity towards these biological targets and bioanalytes. Both the compounds 1 and 2 showed moderate antioxidant activity by scavenging DPPH (1,1-diphenyl-picrylhydrazyl) and ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals. The complexes 1 and 2 were highly cytotoxic against PC3 and MCF-7 cancer cells giving IC50 values ranging from 17 µM to 27 µM.

Comparison of the effect of intraarticular hyaluronic acid and effect of naproxen sodium in patients with osteoarthritis of the knee

Purpose: The purpose of this study was to compare the effects of Intraarticular Hyaluronic Acid( IAHA) injection & Naproxen sodium to reduce pain and functional improvement in patient with osteoarthritis of knee. Methods: Randomized clinical trial was conducted in the Department of Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh during the period from November’2015 to October’2016. A number of total 100 patients of OA knee were selected as per inclusion and exclusion criteria. After proper evaluation and clinical examination patients were undergo study procedure and evaluated by selected assessment criteria. All subjects were enrolled after having informed written consent. 100patients were randomly assigned to 2 groups (Group A=50, and Group B=50). Group A: IAHA series of weekly (20mg/2ml each) for 3 weeks, Exercise and ADL instructions and Group B: NSAIDs (Naproxen 500mg) twice daily for four weeks, Exercise and ADL. Respondents of both groups were assessed to at 4th week, 12th week, and 26th week by OA specific translated and validated Bengali instrument- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire and VAS pain score. The results were expressed as percentage and mean ± SD and level of significance was set at 0.05 and p<0.05 was considered as the level of significant. Student`s t- test and chi-squared (X2) test were done to test the hypothesis which appropriate. Results: 47 patients in group-A and 50 patients in Group-B have completed the study. The improvement of VAS Pain score was 4.02 in group A and 5.62 in group B at week twenty six (26th), which was significant p<0.001. The improvement of WOMAC Pain score was 271.81 in group A and 315.50in group B at week twenty six (26th), which was significant p<0.05.The improvement of WOMAC stiffness score was 107.98 in group A and128.00in group B at week twenty six (26th), which was significant p<0.05. The improvement of WOMAC physical function scorewas 977.66 in group A and B 1314.50in group B at week twenty six (26th), which wassignificant p<0.05. Conclusions: IAHA injection is more beneficial to Naproxen sodium along with exercise and ADL in OA knee.

Exploration of interaction mechanism of tyrosol as a potent anti-inflammatory agent

Drug discovery for a vigorous and feasible lead candidate is a challenging scientific mission as it requires expertise, experience, and huge investment. Natural products and their derivatives having structural diversity are renowned source of therapeutic agents since many years. Tyrosol (a natural phenylethanoid) has been extracted from olive oil, and its structure was confirmed by elemental analysis, FT-IR, FT-NMR, and single crystal X-ray crystallography. The conformational analysis for tyrosol geometry was performed by Gaussian 09 in terms of density functional theory. Validation of bond lengths and bond angles obtained experimentally as well as theoretically were performed with the help of curve fitting analysis, and values of correlation coefficient (R) obtained as 0.988 and 0.984, respectively. The charge transfer within the tyrosol molecule was confirmed by analysis of HOMO→LUMO molecular orbitals. In molecular docking with COX-2 (PDB ID: 5F1A), tyrosol was found to possess satisfactory binding affinity as compared to other NSAIDs (Aspirin, Ibuprofen, and Naproxen) and a COX-2 selective drug (Celecoxib). ADMET prediction, drug-likeness and bioactivity score altogether confirm the lead/drug like potential of tyrosol. Further investigation of simulation quality plot, RMSD and RMSF plots, ligands behavior plot as well as post simulation analysis manifest the consistency of 5F1A-tyrosol complex throughout the 20 ns molecular simulation process that signifies its compactness and stability within the receptor pocket.AbbreviationsADMETAbsorption, Distribution, Metabolism, Excretion and ToxicityÅAngstromCOX-2Cyclooxygenase-2DFTDensity Functional TheoryDMFDimethylformamideFMOFrontier Molecular OrbitalFT-IRFourier-transform Infrared SpectroscopyFT-NMRNuclear Magnetic Resonance SpectroscopyHOMOHighest Occupied Molecular OrbitalLUMOLowest Unoccupied Molecular OrbitalMDMolecular DynamicsNSNanosecondNSAIDsNon-steroidal anti-inflammatory drugsOPEOsiris Property ExplorerRMSDRoot-Mean-Square DeviationRMSFRoot Sean Square FluctuationCommunicated by Ramaswamy H. Sarma

Pooled analysis of tanezumab efficacy and safety with subgroup analyses of phase III clinical trials in patients with osteoarthritis pain of the knee or hip.

PurposeA pooled analysis was conducted to evaluate tanezumab efficacy and safety in patients with osteoarthritis (OA), including subgroup analyses of at-risk patients with diabetes, severe OA symptoms, and those aged ≥65 years.Patients and methodsData from phase III placebo-controlled clinical trials of patients with moderate-to-severe OA of the knee or hip were pooled to evaluate tanezumab efficacy (four trials) and safety (nine trials). Patients received intravenous tanezumab, tanezumab plus an oral NSAID (naproxen, celecoxib, or diclofenac), active comparator (naproxen, celecoxib, diclofenac, or oxycodone), or placebo. Efficacy assessments included change from baseline to week 16 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores, Patient’s Global Assessment (PGA) of OA, and percentage of patients with ≥30%, ≥50%, ≥70%, and ≥90% improvement in WOMAC pain. Safety assessments included adverse event (AE) documentation and physical and neurologic examinations.ResultsTanezumab significantly improved all efficacy end points in the overall population. Efficacy in at-risk patient subgroups was similar to the overall population. Incidence of AEs was highest in the tanezumab plus NSAID group and lowest in the placebo group. Incidence of AEs in the tanezumab monotherapy and active comparator groups was similar. Overall incidence of AEs was similar across subgroups. AEs of abnormal peripheral sensation were more frequently reported in tanezumab-treated patients compared with placebo or active comparator. Patients receiving active comparator had a slightly higher incidence of AEs suggestive of postganglionic sympathetic dysfunction.ConclusionTanezumab consistently provided significant improvement of pain, physical function, and PGA in individuals with OA, including patients with diabetes, severe OA symptoms, or aged ≥65 years. No increased safety risk was observed in at-risk patient subgroups.Trial registrationNCT00733902, NCT00744471, NCT00830063, NCT00863304, NCT00809354, NCT00864097, NCT00863772, NCT01089725, NCT00985621.

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.