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Sample records for naproxen ale

  1. Naproxen

    MedlinePlus

    ... relieve mild pain from headaches, muscle aches, arthritis, menstrual periods, the common cold, toothaches, and backaches. Naproxen is in a class of medications called NSAIDs. It works by stopping the body's production of a substance that causes pain, fever, and inflammation.

  2. Naproxen sodium overdose

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/002507.htm Naproxen sodium overdose To use the sharing features on this page, please enable JavaScript. Naproxen sodium is a nonsteroidal anti-inflammatory drug (NSAID) used ...

  3. Improvement of the physicochemical properties of Co-amorphous naproxen-indomethacin by naproxen-sodium.

    PubMed

    Beyer, Andreas; Grohganz, Holger; Löbmann, Korbinian; Rades, Thomas; Leopold, Claudia S

    2017-06-30

    Improvement of the physicochemical properties of amorphous active pharmaceutical ingredients (APIs) applying the concept of co-amorphisation is a promising alternative to the use of polymer glass solutions. In co-amorphous systems, the physical stability and the dissolution rate of the involved components may be improved in comparison to the respective single amorphous phases. However, for the co-amorphous naproxen-indomethacin model system it has been reported that recrystallization could not be prevented for more than 112days regardless of the applied preparation method and blend ratio In the present study, it was thus tested if the physicochemical properties of co-amorphous naproxen-indomethacin could be optimized by incorporation of the naproxen sodium into the system. Three different co-amorphous systems in nine different molar ratios were prepared by quench-cooling: naproxen-indomethacin (NI), naproxen-sodium-naproxen-indomethacin (NSNI) and naproxen-sodium-indomethacin (NSI). The samples were analyzed by XRPD, FTIR, DSC and by intrinsic dissolution experiments to investigate the influence of naproxen-sodium on the resulting physicochemical properties of the systems. With the three systems, fully amorphous samples with single glass transition temperatures could be prepared with naproxen molar fractions up to 0.7. The NSI and NSNI systems showed up to about 40°C higher Tgs than the NI system. Furthermore, no recrystallization occurred during 270d of storage with the NSI and NSNI samples that were initially amorphous. Moreover, with the NSI system, the intrinsic dissolution rate of naproxen and indomethacin was improved by a factor of 2 compared to the unmodified NI system. In conclusion, the physical stability as well as the dissolution rate was significantly improved if partial or full exchange of naproxen by its sodium salt was performed, which may present a general optimization method to improve co-amorphous systems. Copyright © 2017 Elsevier B.V. All

  4. Massive naproxen overdose with serial serum levels.

    PubMed

    Al-Abri, Suad A; Anderson, Ilene B; Pedram, Fatehi; Colby, Jennifer M; Olson, Kent R

    2015-03-01

    Massive naproxen overdose is not commonly reported. Severe metabolic acidosis and seizure have been described, but the use of renal replacement therapy has not been studied in the context of overdose. A 28-year-old man ingested 70 g of naproxen along with an unknown amount of alcohol in a suicidal attempt. On examination in the emergency department 90 min later, he was drowsy but had normal vital signs apart from sinus tachycardia. Serum naproxen level 90 min after ingestion was 1,580 mg/L (therapeutic range 25-75 mg/L). He developed metabolic acidosis requiring renal replacement therapy using sustained low efficiency dialysis (SLED) and continuous venovenous hemofiltration (CVVH) and had recurrent seizure activity requiring intubation within 4 h from ingestion. He recovered after 48 h. Massive naproxen overdose can present with serious toxicity including seizures, altered mental status, and metabolic acidosis. Hemodialysis and renal replacement therapy may correct the acid base disturbance and provide support in cases of renal impairment in context of naproxen overdose, but further studies are needed to determine the extraction of naproxen.

  5. Single dose oral naproxen and naproxen sodium for acute postoperative pain (Review)

    PubMed Central

    Mason, L; Edwards, JE; Moore, RA; McQuay, HJ

    2014-01-01

    Background Postoperative pain is often poorly managed. Treatment options include a range of drug therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) of which naproxen is one. Naproxen is used to treat a variety of painful conditions including acute postoperative pain, and is often combined with sodium to improve its solubility for oral administration. Naproxen sodium 550 mg (equivalent to 500 mg of naproxen) is considered to be an effective dose for treating postoperative pain but to date no systematic review of the effectiveness of naproxen/naproxen sodium at different doses has been published. Objectives To assess the efficacy, safety and duration of action of a single oral dose of naproxen or naproxen sodium for acute postoperative pain in adults. Search strategy We searched The Cochrane Library, MEDLINE, EMBASE and the Oxford Pain Relief Database for relevant studies. Additional studies were identified from the reference list of retrieved reports. The most recent search was undertaken in July 2004. Selection criteria Included studies were randomised, double blind, placebo-controlled trials of a single dose of orally administered naproxen or naproxen sodium in adults with moderate to severe acute postoperative pain. Data collection and analysis Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50% pain relief over four to six hours. Relative risk estimates (RR) and the number-needed-to-treat (NNT) for at least 50% pain relief were then calculated. Information was sought on the percentage of patients experiencing any adverse event, and the number-needed-to-harm was derived. Time to remedication was also estimated. Main results Ten trials (996 patients) met the inclusion criteria: nine assessed naproxen sodium; one combined the results from two small trials of naproxen alone. Included studies scored well for methodological quality. Meta-analysis of six trials (500

  6. ALES: An Innovative Argument-Learning Environment

    ERIC Educational Resources Information Center

    Abbas, Safia; Sawamura, Hajime

    2010-01-01

    This paper presents the development of an Argument-Learning System (ALES). The idea is based on the AIF (argumentation interchange format) ontology using "Walton theory". ALES uses different mining techniques to manage a highly structured arguments repository. This repository was designed, developed and implemented by the authors. The aim is to…

  7. Clinical Pharmacology and Cardiovascular Safety of Naproxen.

    PubMed

    Angiolillo, Dominick J; Weisman, Steven M

    2017-04-01

    The voluntary withdrawal of Vioxx (rofecoxib) from the market in 2004, as well as the 2005 and 2014 US FDA Advisory Committee meetings about non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular risk, have raised questions surrounding the use of NSAIDs in at-risk populations. This paper discusses the cardiovascular safety profile of naproxen in the context of the NSAID class. The balance of evidence suggests that cardiovascular risk correlates with cyclooxygenase (COX)-2 selectivity, and the low COX-2 selectivity of naproxen results in a lower cardiovascular risk than that of other NSAIDs. The over-the-counter (OTC) use of naproxen is expected to pose minimal cardiovascular risk; however, the benefit-risk ratio and appropriate use should be considered at an individual patient level, particularly to assess underlying conditions that may increase the risk of events. Likewise, regulatory authorities should revisit label information periodically to ensure labeling reflects the current understanding of benefits and risks.

  8. 21 CFR 520.1468 - Naproxen granules.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... pain and lameness exhibited with arthritis, as well as myositis and other soft tissue diseases of the..., administer 10 milligrams naproxen per kilogram of animal body weight twice daily as top dressing in the...

  9. 21 CFR 520.1468 - Naproxen granules.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... pain and lameness exhibited with arthritis, as well as myositis and other soft tissue diseases of the..., administer 10 milligrams naproxen per kilogram of animal body weight twice daily as top dressing in the...

  10. 21 CFR 520.1468 - Naproxen granules.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... pain and lameness exhibited with arthritis, as well as myositis and other soft tissue diseases of the..., administer 10 milligrams naproxen per kilogram of animal body weight twice daily as top dressing in the...

  11. 21 CFR 520.1468 - Naproxen granules.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... pain and lameness exhibited with arthritis, as well as myositis and other soft tissue diseases of the..., administer 10 milligrams naproxen per kilogram of animal body weight twice daily as top dressing in the...

  12. 21 CFR 520.1468 - Naproxen granules.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1468 Naproxen granules. (a... musculoskeletal system of the horse. (2)(i) For oral maintenance therapy following initial intravenous dosage...

  13. CHEMOPREVENTIVE EFFICACY OF NAPROXEN AND NO-NAPROXEN IN RODENT MODELS OF COLON, URINARY BLADDER, AND MAMMARY CANCERS

    PubMed Central

    Steele, Vernon E.; Rao, Chinthalapally V.; Zhang, Yuting; Patlolla, Jagan; Boring, Daniel; Kopelovich, Levy; Juliana, M. Margaret; Grubbs, Clinton J.; Lubet, Ronald A.

    2009-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been highly effective in preventing colon, urinary bladder, and skin cancer preclinically; and also in clinical trials of colon adenoma formation. However, certain NSAIDs cause gastrointestinal (GI) ulceration and may increase cardiovascular (CV) events. Naproxen appears to cause the lowest CV events of the common NSAIDs other than aspirin. NO-naproxen was tested based on the finding that adding a nitric oxide (NO) group to NSAIDs may help alleviate GI toxicity. In the azoxymethane (AOM)-induced rat colon aberrant crypt foci (ACF) model, naproxen administered at 200 and 400 ppm in the diet reduced mean ACFs in the colon by about 45–60%, respectively. NO-naproxen was likewise administered in the diet at roughly equimolar doses (300 and 600 ppm), and reduced total ACF by 20–40%, respectively. In the hydroxybutyl (butyl) nitrosamine (OH-BBN) rat urinary bladder cancer model, NO-naproxen was given at 183 ppm or 550 ppm in the diet, and naproxen at 128 ppm. The NO-naproxen groups had 77% and 73% decreases, respectively, in the development of large urinary bladder tumors, while the 128 ppm naproxen group also showed a strong decrease (69%). If treatments were started three months after OH-BBN, NO-naproxen (550 ppm) and naproxen (400 ppm) were also highly effective (86–94% decreases). In the methylnitrosourea (MNU)-induced mammary cancer model in rats, NO-naproxen and naproxen showed non-significant inhibitions (12 and 24%) at 550 and 400 ppm, respectively. These data show that both naproxen and NO-naproxen are effective agents against urinary bladder and colon, but not mammary, carcinogenesis. PMID:19892664

  14. Microbial models of mammalian metabolism: microbial transformation of naproxen.

    PubMed

    el Sayed, K A

    2000-12-01

    Preparative-scale fermentation of S-naproxen, the known antiinflammatory, analgesic and antipyretic drug, with Cunninghamella elegans ATCC 9245 afforded S-demethylnaproxen, the known human active metabolite of naproxen, in a 90% yield. Demethylnaproxen was also detected as the major metabolite of naproxen using Cunninghamella blakesleeana ATCC 8688a. A review of the previous microbial metabolism studies using the fungi Cunninghamella species suggested that it could be a plausible in vitro predictor for mammalian metabolism.

  15. Ecotoxicity of naproxen and its phototransformation products.

    PubMed

    Isidori, Marina; Lavorgna, Margherita; Nardelli, Angela; Parrella, Alfredo; Previtera, Lucio; Rubino, Maria

    2005-09-15

    The occurrence of pharmaceuticals in the environment is of great concern and only few data are available about the adverse effects of such molecules and their derivatives on non-target aquatic organisms. This study was designed to assess the toxic potential of Naproxen, a nonsteroidal anti-inflammatory, Naproxen Na, its freely water soluble sodium salt and their photoproducts in the aquatic environment. Bioassays were performed on algae, rotifers and microcrustaceans to assess acute and chronic toxicity. Furthermore, possible genotoxic effects of photoderivatives were investigated using SOS chromotest and Ames fluctuation test. The results showed that photoproducts were more toxic than the parent compounds both for acute and chronic values, while genotoxic and mutagenic effects were not found. These findings suggested the opportunity to consider derivatives in ecotoxicology assessment of drugs.

  16. Sensitization of meningeal nociceptors: inhibition by naproxen

    PubMed Central

    Levy, Dan; Zhang, Xi-Chun; Jakubowski, Moshe; Burstein, Rami

    2009-01-01

    Migraine attacks associated with throbbing (manifestation of peripheral sensitization) and cutaneous allodynia (manifestation of central sensitization) are readily terminated by intravenous administration of a non-selective cyclooxygenase (COX) inhibitor. Evidence that sensitization of rat central trigeminovascular neurons was also terminated in vivo by non-selective COX inhibition has led us to propose that COX inhibitors may act centrally in the dorsal horn. In the present study, we examined whether COX inhibition can also suppress peripheral sensitization in meningeal nociceptors. Using single-unit recording in the trigeminal ganglion in vivo, we found that intravenous infusion of naproxen, a non-selective COX inhibitor, reversed measures of sensitization induced in meningeal nociceptors by prior exposure of the dura to inflammatory soup (IS): ongoing activity of Aδ- and C-units and their response magnitude to mechanical stimulation of the dura, which were enhanced after IS, returned to baseline after naproxen infusion. Topical application of naproxen or the selective COX-2 inhibitor N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) onto the dural receptive field of Aδ- and C-unit nociceptors also reversed the neuronal hyper-responsiveness to mechanical stimulation of the dura. The findings suggest that local COX activity in the dura could mediate the peripheral sensitization that underlies migraine headache. PMID:18333963

  17. The Myotoxic Effects of Microencapsulated Naproxen and Carrier Polymer After Intramuscular Injection in Rats

    DTIC Science & Technology

    1996-10-10

    THE MYOTOXIC EFFECTS OF MICROENCAPSULATED NAPROXEN AND CARRIER POLYMER AFTER INTRAMUSCULAR INJECTION IN RATS A Masters Thesis By Kevin J. Bohan... Microencapsulated Naproxen and Carrier Polymer After Intramuscular Injection in Rats" beyond brief excerpts is with the pennission of the copyright...naproxen to be microencapsulated (MEC) for parenteral use. Intramuscular MEC naproxen could provide greater pain relief than ketoralac with a longer

  18. Enzymes Involved in Naproxen Degradation by Planococcus sp. S5.

    PubMed

    Wojcieszyńska, Danuta; Domaradzka, Dorota; Hupert-Kocurek, Katarzyna; Guzik, Urszula

    2016-01-01

    Naproxen is a one of the most popular non-steroidal anti-inflammatory drugs (NSAIDs) entering the environment as a result of high consumption. For this reason, there is an emerging need to recognize mechanisms of its degradation and enzymes engaged in this process. Planococcus sp. S5 is a gram positive strain able to degrade naproxen in monosubstrate culture (27%). However, naproxen is not a sufficient growth substrate for this strain. In the presence of benzoate, 4-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid or vanillic acid as growth substrates, the degradation of 21.5%, 71.71%, 14.75% and 8.16% of naproxen was observed respectively. It was shown that the activity of monooxygenase, hydroxyquinol 1,2-dioxygenase, protocatechuate 3,4-dioxygenase and protocatechuate 4,5-dioxyegnase in strain S5 was induced after growth of the strain with naproxen and 4-hydroxybenzoate. Moreover, in the presence of naproxen activity of gentisate 1,2-dioxygenase, enzyme engaged in 4-hydroxybenzoate metabolism, was completely inhibited. The obtained results suggest that monooxygenase and hydroxyquinol 1,2-dioxygenase are the main enzymes in naproxen degradation by Planococcus sp. S5.

  19. Periorbital edema associated with separate courses of ibuprofen and naproxen.

    PubMed

    Balas, Morad; Plakogiannis, Roda; Sinnett, Mark

    2010-06-01

    A case of periorbital edema associated with separate courses of ibuprofen and naproxen is reported. An 80-year-old African- American woman with a history of osteoarthritis and hypertension came to the clinic. Her medication regimen included fosinopril sodium 40 mg daily, which she began two years prior. She had no known drug allergies and denied consuming any over-the-counter medications or herbal substances and reported a negative atopic status. She had seen her primary care provider several days prior and reported pain in the hands, fingers, and ankles, which would escalate in the morning and progressively lessen during the course of the day. Her physician prescribed naproxen 375 mg every eight hours as needed. After ingesting two doses of naproxen, she developed itching, swelling, and erythema around the left eye that became progressively worse and spread to the right eye. She contacted her primary care physician, who instructed her to discontinue the naproxen, and the reaction resolved within three days. The patient was maintained on acetaminophen for the arthritic pain with no issues. Approximately three months prior, ibuprofen 600 mg every eight hours as needed was prescribed for the same pain. She stated that after ingesting two doses of ibuprofen, she experienced a reaction similar to that recently experienced with naproxen. At that time, she was instructed to discontinue the ibuprofen, and her symptoms resolved. An elderly woman developed periorbital edema after taking ibuprofen on one occasion and naproxen on another.

  20. Sumatriptan/Naproxen Sodium: A Review in Migraine.

    PubMed

    Syed, Yahiya Y

    2016-01-01

    Sumatriptan/naproxen sodium (Treximet®) is a fixed-dose combination of a serotonin 5-HT1B/1D receptor agonist (sumatriptan) and an NSAID (naproxen sodium), approved in the USA for the acute treatment of migraine with or without aura in adolescents and adults. In a randomized, phase 3 trial in adolescents, significantly more sumatriptan/naproxen sodium than placebo recipients were pain-free at 2 h. Similarly, in a pair of randomized phase 3 trials in adults, significantly more sumatriptan/naproxen sodium than placebo recipients had relief from migraine symptoms at 2 h, and the combination was more effective than individual components in terms of sustained (2-24 h) pain-free response rate. Sumatriptan/naproxen sodium was generally well tolerated, with ≤11 % of adolescents and ≤22 % of adults reporting treatment-related adverse events in the key clinical trials. The most common adverse reactions were nasopharyngitis, hot flushes and muscle tightness in adolescents, and dizziness, pain or pressure sensations, nausea, somnolence, dry mouth, dyspepsia and paraesthesia in adults. Based on current data, sumatriptan/naproxen sodium is a useful option for the acute treatment of migraine in adolescents and adults. The fixed-dose combination may reduce pill burden and improve adherence in some patients.

  1. Instantons on ALE spaces and orbifold partitions

    NASA Astrophysics Data System (ADS)

    Dijkgraaf, Robbert; Sułkowski, Piotr

    2008-03-01

    We consider Script N = 4 theories on ALE spaces of Ak-1 type. As is well known, their partition functions coincide with Ak-1 affine characters. We show that these partition functions are equal to the generating functions of some peculiar classes of partitions which we introduce under the name 'orbifold partitions'. These orbifold partitions turn out to be related to the generalized Frobenius partitions introduced by G. E. Andrews some years ago. We relate the orbifold partitions to the blended partitions and interpret explicitly in terms of a free fermion system.

  2. Serum concentrations of salicylate and naproxen during concurrent therapy in patients with rheumatoid arthritis.

    PubMed

    Furst, D E; Sarkissian, E; Blocka, K; Cassell, S; Dromgoole, S; Harris, E R; Hirschberg, J M; Josephson, N; Paulus, H E

    1987-10-01

    The kinetic interaction between salicylate and naproxen was investigated in 25 rheumatoid arthritis patients. Kinetic interactions were tested in serum after patients had been on each drug regimen for 1 month. Salicylate decreased serum naproxen concentration from 89.5 mg/liter to 65.9 mg/liter (P less than 0.001) and increased serum naproxen clearance by 56%. Naproxen had minimal effect on serum salicylate concentrations.

  3. A coupled ALE-AMR method for shock hydrodynamics

    DOE PAGES

    Waltz, J.; Bakosi, J.

    2018-03-05

    We present a numerical method combining adaptive mesh refinement (AMR) with arbitrary Lagrangian-Eulerian (ALE) mesh motion for the simulation of shock hydrodynamics on unstructured grids. The primary goal of the coupled method is to use AMR to reduce numerical error in ALE simulations at reduced computational expense relative to uniform fine mesh calculations, in the same manner that AMR has been used in Eulerian simulations. We also identify deficiencies with ALE methods that AMR is able to mitigate, and discuss the unique coupling challenges. The coupled method is demonstrated using three-dimensional unstructured meshes of up to O(10 7) tetrahedral cells.more » Convergence of ALE-AMR solutions towards both uniform fine mesh ALE results and analytic solutions is demonstrated. Speed-ups of 5-10× for a given level of error are observed relative to uniform fine mesh calculations.« less

  4. A coupled ALE-AMR method for shock hydrodynamics

    SciTech Connect

    Waltz, J.; Bakosi, J.

    We present a numerical method combining adaptive mesh refinement (AMR) with arbitrary Lagrangian-Eulerian (ALE) mesh motion for the simulation of shock hydrodynamics on unstructured grids. The primary goal of the coupled method is to use AMR to reduce numerical error in ALE simulations at reduced computational expense relative to uniform fine mesh calculations, in the same manner that AMR has been used in Eulerian simulations. We also identify deficiencies with ALE methods that AMR is able to mitigate, and discuss the unique coupling challenges. The coupled method is demonstrated using three-dimensional unstructured meshes of up to O(10 7) tetrahedral cells.more » Convergence of ALE-AMR solutions towards both uniform fine mesh ALE results and analytic solutions is demonstrated. Speed-ups of 5-10× for a given level of error are observed relative to uniform fine mesh calculations.« less

  5. Cometabolic Degradation of Naproxen by Planococcus sp. Strain S5.

    PubMed

    Domaradzka, Dorota; Guzik, Urszula; Hupert-Kocurek, Katarzyna; Wojcieszyńska, Danuta

    Naproxen is a non-steroidal anti-inflammatory drug frequently detected in the influent and effluent of sewage treatment plants. The Gram-positive strain Planococcus sp. S5 was able to remove approximately 30 % of naproxen after 35 days of incubation in monosubstrate culture. Under cometabolic conditions, with glucose or phenol as a growth substrate, the degradation efficiency of S5 increased. During 35 days of incubation, 75.14 ± 1.71 % and 86.27 ± 2.09 % of naproxen was degraded in the presence of glucose and phenol, respectively. The highest rate of naproxen degradation observed in the presence of phenol may be connected with the fact that phenol is known to induce enzymes responsible for aromatic ring cleavage. The activity of phenol monooxygenase, naphthalene monooxygenase, and hydroxyquinol 1,2-dioxygenase was indicated in Planococcus sp. S5 culture with glucose or phenol as a growth substrate. It is suggested that these enzymes may be engaged in naproxen degradation.

  6. Preparation and In vitro Evaluation of Naproxen Suppositories

    PubMed Central

    Hargoli, S.; Farid, J.; Azarmi, S. H.; Ghanbarzadeh, S.; Zakeri-Milani, P.

    2013-01-01

    The aim of this work was to develop the best formulations for naproxen suppositories. The effects of different bases and surfactants on the physicochemical characteristics of the suppositories were determined by several tests such as weight variation, melting point, assay, hardness, and release rate. All formulations met the standard criteria for tested physicochemical parameters; weight variation (97-112%), content uniformity (97-105%), melting point (4.66-8.7 min) and hardness tests (>5400 g). Based on release rate studies, hydrophilic, and lipophilic bases without surfactants were not suitable bases for naproxen suppository. Amongst the formulations containing surfactants only Witepsol H15 with 0.5% w/w of Tween 80 and Witepsol W35 with 0.5% of cetylpyridinium chloride were suitable and released nearly complete drug during 30 and 60 min, respectively. This study demonstrates the effects of incorporation of known agents on the in vitro release characteristics of naproxen suppository. PMID:24019561

  7. Alteration of plasma prednisolone levels by indomethacin and naproxen.

    PubMed Central

    Rae, S A; Williams, I A; English, J; Baylis, E M

    1982-01-01

    Eleven patients with stable rheumatoid disease (RD) who were receiving regular corticosteroid therapy (CS) were investigated to discover the effect on plasma prednisolone levels of additional therapy with the non-steroidal anti-inflammatory (NSAI) drugs, indomethacin and naproxen. There was a highly significant (P less than 0.001) increase in free prednisolone levels after concurrent therapy with either indomethacin or naproxen for 2 weeks. Total prednisolone levels were unchanged. These results could provide an explanation for clinical reports that these two NSAI drugs possess a steroid-sparing effect. PMID:7126420

  8. Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery.

    PubMed

    Bali, Cagla; Ergenoglu, Pinar; Ozmete, Ozlem; Akin, Sule; Ozyilkan, Nesrin Bozdogan; Cok, Oya Yalcin; Aribogan, Anis

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18(th) hour on movement (p<0.05). The median time to the first demand of PCA was shorter in Group N compared with Group NC (p<0.001). Meperidine consumption was higher in Group N compared with Group NC (p<0.001). There was no difference between groups with respect to side effects (p>0.05). The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  9. [Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery].

    PubMed

    Bali, Cagla; Ergenoglu, Pinar; Ozmete, Ozlem; Akin, Sule; Ozyilkan, Nesrin Bozdogan; Cok, Oya Yalcin; Aribogan, Anis

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18(th) hour on movement (p<0.05). The median time to the first demand of PCA was shorter in Group N compared with Group NC (p<0.001). Meperidine consumption was higher in Group N compared with Group NC (p<0.001). There was no difference between groups with respect to side effects (p>0.05). The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  10. Non-steroidal anti-inflammatory drug naproxen destabilizes Aβ amyloid fibrils: A molecular dynamics investigation

    PubMed Central

    Takeda, Takako; Kumar, Rashmi; Raman, E. Prabhu; Klimov, Dmitri K.

    2010-01-01

    Using implicit solvent model and replica exchange molecular dynamics we examine the propensity of non-steroidal anti-inflammatory drug, naproxen, to interfere with Aβ fibril growth. We also compare the anti-aggregation propensity of naproxen with that of ibuprofen. Naproxen anti-aggregation effect is influenced by two factors. Similar to ibuprofen, naproxen destabilizes binding of incoming Aβ peptides to the fibril due to direct competition between the ligands and the peptides for the same binding location on the fibril surface (the edge). However, in contrast to ibuprofen naproxen binding also alters the conformational ensemble of Aβ monomers by promoting β-structure. The second factor weakens naproxen anti-aggregation effect. These findings appear to explain the experimental observations, according to which naproxen binds to Aβ fibril with higher affinity than ibuprofen, yet produces weaker anti-aggregation action. PMID:20979356

  11. An AMR capable finite element diffusion solver for ALE hydrocodes [An AMR capable diffusion solver for ALE-AMR

    SciTech Connect

    Fisher, A. C.; Bailey, D. S.; Kaiser, T. B.

    2015-02-01

    Here, we present a novel method for the solution of the diffusion equation on a composite AMR mesh. This approach is suitable for including diffusion based physics modules to hydrocodes that support ALE and AMR capabilities. To illustrate, we proffer our implementations of diffusion based radiation transport and heat conduction in a hydrocode called ALE-AMR. Numerical experiments conducted with the diffusion solver and associated physics packages yield 2nd order convergence in the L 2 norm.

  12. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis.

    PubMed

    Nissen, Steven E; Yeomans, Neville D; Solomon, Daniel H; Lüscher, Thomas F; Libby, Peter; Husni, M Elaine; Graham, David Y; Borer, Jeffrey S; Wisniewski, Lisa M; Wolski, Katherine E; Wang, Qiuqing; Menon, Venu; Ruschitzka, Frank; Gaffney, Michael; Beckerman, Bruce; Berger, Manuela F; Bao, Weihang; Lincoff, A Michael

    2016-12-29

    The cardiovascular safety of celecoxib, as compared with nonselective nonsteroidal antiinflammatory drugs (NSAIDs), remains uncertain. Patients who required NSAIDs for osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk were randomly assigned to receive celecoxib, ibuprofen, or naproxen. The goal of the trial was to assess the noninferiority of celecoxib with regard to the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke. Noninferiority required a hazard ratio of 1.12 or lower, as well as an upper 97.5% confidence limit of 1.33 or lower in the intention-to-treat population and of 1.40 or lower in the on-treatment population. Gastrointestinal and renal outcomes were also adjudicated. A total of 24,081 patients were randomly assigned to the celecoxib group (mean [±SD] daily dose, 209±37 mg), the naproxen group (852±103 mg), or the ibuprofen group (2045±246 mg) for a mean treatment duration of 20.3±16.0 months and a mean follow-up period of 34.1±13.4 months. During the trial, 68.8% of the patients stopped taking the study drug, and 27.4% of the patients discontinued follow-up. In the intention-to-treat analyses, a primary outcome event occurred in 188 patients in the celecoxib group (2.3%), 201 patients in the naproxen group (2.5%), and 218 patients in the ibuprofen group (2.7%) (hazard ratio for celecoxib vs. naproxen, 0.93; 95% confidence interval [CI], 0.76 to 1.13; hazard ratio for celecoxib vs. ibuprofen, 0.85; 95% CI, 0.70 to 1.04; P<0.001 for noninferiority in both comparisons). In the on-treatment analysis, a primary outcome event occurred in 134 patients in the celecoxib group (1.7%), 144 patients in the naproxen group (1.8%), and 155 patients in the ibuprofen group (1.9%) (hazard ratio for celecoxib vs. naproxen, 0.90; 95% CI, 0.71 to 1.15; hazard ratio for celecoxib vs. ibuprofen, 0.81; 95% CI, 0.65 to 1.02; P<0.001 for noninferiority in

  13. Naproxen-PC: a GI safe and highly effective anti-inflammatory.

    PubMed

    Lichtenberger, L M; Romero, J J; Dial, E J; Moore, J E

    2009-02-01

    We have been developing a family of phosphatidylcholine (PC)-associated NSAIDs, which appear to have improved GI safety and therapeutic efficacy in both rodent model systems and pilot clinical trials. As naproxen has been demonstrated to be associated with the lowest cardiovascular adverse events in comparison with both COX-2 selective inhibitors and conventional NSAIDs, we have been developing a Naproxen-PC formulation for evaluation in animal models and clinical trials. We have determined that an oil-based formulation of naproxen and triple strength soy lecithin provides excellent GI protection in both: 1) an acute NSAID-induced intestinal bleeding model in rats pretreated with L-NAME that are intragastrically administered a single dose of naproxen (at a dose of 50 mg/kg) vs the equivalent dose of Naproxen-PC; and 2) a more chronic model (at a naproxen dose of 25 mg/kg BID) in rats that have pre-existing hindpaw inflammation (induced with a intradermal injection of Complete Freund's Adjuvant/CFA). Both models demonstrate the superior GI safety of Naproxen-PC vs naproxen while this novel formulation had significant anti-inflammatory efficacy to reduce hindpaw edema and the generation of PGE(2) in the collected joint synovial fluid. Naproxen-PC appears to induce significantly less GI injury and bleeding in two rodent model systems while maintaining anti-inflammatory and COX-inhibitory activity.

  14. Physicochemical characterization and structural evaluation of a specific 2:1 cocrystal of naproxen-nicotinamide.

    PubMed

    Ando, Shigeru; Kikuchi, Junko; Fujimura, Yuko; Ida, Yasuo; Higashi, Kenjirou; Moribe, Kunikazu; Yamamoto, Keiji

    2012-09-01

    Physicochemical characterization and structural evaluation of a 2:1 naproxen-nicotinamide cocrystal were performed. The 2:1 cocrystal showed rapid naproxen dissolution and less water vapor adsorption, indicating better pharmaceutical properties of naproxen. The unique 2:1 cocrystal formation was evaluated by solid-state nuclear magnetic resonance (NMR). The assignments of all H and (13) C peaks for naproxen and the cocrystal were performed using dipolar-insensitive nuclei enhanced by polarization transfer and (1) H-(13) C cross-polarization (CP)-heteronuclear correlation (HETCOR) NMR measurements. The (13) C chemical shift revealed that two naproxen molecules and one nicotinamide molecule existed in the asymmetric unit of the cocrystal. The (1) H chemical shifts indicated that the carboxylic group of the naproxen in the cocrystal was nonionized, and the CH-π interaction between naproxens was very strong. From the (1) H-(13) C CP-HETCOR NMR spectrum with contact time of 5 ms, two different synthons, carboxylic acid-amide and carboxylic acid-pyridine ring, were found between naproxen and nicotinamide. Single-crystal X-ray analysis, which supported the solid-state NMR results, clarified the geometry and intermolecular interactions in more detail. The structure is unique among pharmaceutical cocrystals because each carboxyl group of the two naproxens formed different intermolecular synthons. Copyright © 2012 Wiley Periodicals, Inc.

  15. Functionalized β-cyclodextrin based potentiometric sensor for naproxen determination.

    PubMed

    Lenik, Joanna; Łyszczek, Renata

    2016-04-01

    Potentiometric sensors based on neutral β-cyclodextrins: (2-hydroxypropyl)-β-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, heptakis(2,3,6-tri-O-benzoyl)-β-cyclodextrin and anionic β-cyclodextrin: (2-hydroxy-3-N,N,N-trimethylamino)propyl-β-cyclodextrin chloride for naproxen are described. Inclusion complexes of naproxen with the above-mentioned cyclodextrins were studied using IR spectroscopy. The electrode surface was made from PVC membranes doped with the appropriate β-cyclodextrin as ionophores and quaternary ammonium chlorides as positive charge additives that were dispersed in plasticizers. The optimum membrane contains heptakis(2,3,6-tri-O-benzoyl)-β-cyclodextrin, o-nitrophenyloctyl ether and tetraoctyl ammonium chloride as a lipophilic salt. The electrode is characterized by a Nernstian response slope of -59.0 ± 0.5 mV decade(-1) over the linear range of 5.0 × 10(-5)-1.0 × 10(-2) mol L(-1) and the detection limit 1.0 × 10(-5) mol L(-1), as well as the response time 10s. It can be used in the pH range 6.2-8.5 for 10 months without any considerable deterioration. Incorporation of β-cyclodextrins improved the electrode selectivity towards naproxen ions from several inorganic and organic interferents and some common drug excipients due to concovalent interactions (host molecule-guest molecule). The notable advantages of the naproxen-selective electrode include its high sensitivity, high selectivity, cost-effectiveness as well as accurate and comfortable application in drug analysis and milk samples. Copyright © 2015. Published by Elsevier B.V.

  16. Degradation of naproxen by UV, VUV photolysis and their combination.

    PubMed

    Arany, Eszter; Szabó, Rita Katalin; Apáti, László; Alapi, Tünde; Ilisz, István; Mazellier, Patrick; Dombi, András; Gajda-Schrantz, Krisztina

    2013-11-15

    Naproxen is a widely used nonsteroidal anti-inflammatory drug. Recently, this medicine was detected both in natural waters (up to 1.5 μg L(-1)) and in sewage treatment plant effluents (up to 5.2 μg L(-1)). Moreover, naproxen is only partly eliminated by classical processes used in sewage treatment plants. Therefore, its degradation is of utmost interest. Advanced oxidation processes proved to be the most suitable methods for the elimination of persistent organic contaminants. In this work ultraviolet (UV, 254 nm), vacuum ultraviolet photolysis (VUV, 172 nm) and their combination (UV/VUV, 254/185 nm) were investigated. The efficiency of the methods increased in the following order: UV < VUV < UV/VUV photolysis. However, VUV irradiation was found to mineralize the contaminant molecule most effectively. The chemical structures of three out of four aromatic by-products and of some aliphatic carboxylic acids were presumed. The effects of dissolved O2 and the initial concentration of naproxen on the degradation were also investigated. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Hydrogen sulfide releasing naproxen offers better anti-inflammatory and chondroprotective effect relative to naproxen in a rat model of zymosan induced arthritis.

    PubMed

    Dief, A E; Mostafa, D K; Sharara, G M; Zeitoun, T H

    2015-04-01

    Hydrogen sulfide (H2S) is rapidly gaining ground as a physiological mediator of inflammation, but there is no clear consensus as to its precise role in inflammation. Therefore, this study was undertaken to evaluate the effects of ATB-346 as a novel H2S-releasing naproxen compared to naproxen, as a traditional non-steroidal anti-inflammatory drug on zymosan induced mono-arthritis in rats. Male Wistar rats (n=48) were randomly assigned to four main groups: normal control, untreated arthritis, Naproxen and ATB-346 treated groups. Mono-arthritis was induced by intra-articular injection of zymosan into the knee joints. Mechanical hypernociception and joint swelling were evaluated at 6 hours and 5 days. Inflammatory cellular recruitment and adherence, tumor necrosis factor alpha, nuclear factor kappa β, total sulfide levels, and histological changes were evaluated in knee lavages, blood or joint tissues at selected time points. Zymosan injection evoked knee inflammation and pain as characterized by mechanical hypernociception, impaired gait, joint swelling with inflammatory exudation and histological changes. Treatment with ATB-346 attenuated nociceptive responses, inflammatory cellular and biochemical changes in comparison to naproxen. Only ATB-346 was able to suppress neutrophil adherence and to preserve normal articular structure. H2S releasing naproxen represents an advancement over the parent drug, naproxen. Apart from the superior anti-inflammatory and anti-noceiceptive activity, ATB-346 offered a distinguished chondroprotective effect and is almost devoid from naproxen deleterious effects on articular cartilage.

  18. Molecular Basis for Cyclooxygenase Inhibition by the Non-steroidal Anti-inflammatory Drug Naproxen

    SciTech Connect

    Duggan, Kelsey C.; Walters, Matthew J.; Musee, Joel

    Naproxen ((S)-6-methoxy-{alpha}-methyl-2-naphthaleneacetic acid) is a powerful non-selective non-steroidal anti-inflammatory drug that is extensively used as a prescription and over-the-counter medication. Naproxen exhibits gastrointestinal toxicity, but its cardiovascular toxicity may be reduced compared with other drugs in its class. Despite the fact that naproxen has been marketed for many years, the molecular basis of its interaction with cyclooxygenase (COX) enzymes is unknown. We performed a detailed study of naproxen-COX-2 interactions using site-directed mutagenesis, structure-activity analysis, and x-ray crystallography. The results indicate that each of the pendant groups of the naphthyl scaffold are essential for COX inhibition, and only minimal substitutions aremore » tolerated. Mutation of Trp-387 to Phe significantly reduced inhibition by naproxen, a result that appears unique to this inhibitor. Substitution of S or CH2 for the O atom of the p-methoxy group yielded analogs that were not affected by the W387F substitution and that exhibited increased COX-2 selectivity relative to naproxen. Crystallization and x-ray analysis yielded structures of COX-2 complexed to naproxen and its methylthio analog at 1.7 and 2.3 {angstrom} resolution, respectively. The combination of mutagenesis, structure analysis, and x-ray crystallography provided comprehensive information on the unique interactions responsible for naproxen binding to COX-2.« less

  19. Acute toxicity and histopathological effects of naproxen in zebrafish (Danio rerio) early life stages.

    PubMed

    Li, Qian; Wang, Peipei; Chen, Ling; Gao, Hongwen; Wu, Lingling

    2016-09-01

    Zebrafish (Danio rerio) embryos and larvae were selected to investigate the potential risk and aquatic toxicity of a widely used pharmaceutical, naproxen. The acute toxicity of naproxen to embryos and larvae was measured, respectively. The histopathology was investigated in the liver of zebrafish larvae after 8-day embryo-larvae exposure to naproxen. The values of 96-h LC50 were 115.2 mg/L for embryos and 147.6 mg/L for larvae, indicating that zebrafish embryos were more sensitive than larvae to naproxen exposure. Large suites of symptoms were induced in zebrafish (D. rerio) early life stages by different dosages of naproxen, including hatching inhibition, lower heart rate, and morphological abnormalities. The most sensitive sub-lethal effect caused by naproxen was pericardial edema, the 72-h EC50 values of which for embryos and larvae were 98.3 and 149.0 mg/L, respectively. In addition, naproxen-treated zebrafish larvae exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. The results indicated that naproxen is a potential threat to aquatic organisms.

  20. Biodegradation of naproxen by freshwater algae Cymbella sp. and Scenedesmus quadricauda and the comparative toxicity.

    PubMed

    Ding, Tengda; Lin, Kunde; Yang, Bo; Yang, Mengting; Li, Juying; Li, Wenying; Gan, Jay

    2017-08-01

    Naproxen is one of the most prevalent pharmaceuticals and of great environment concern. Information about bioremediation of naproxen by algae remains limited and no study has been reported on the degradation mechanism and the toxicity of NPX on algae. In this study, both Cymbella sp. and Scenedesmus quadricauda showed complete growth inhibition (100%) at 100mgL -1 within 24h. Biochemical characteristics including chlorophyll a, carotenoid contents and enzyme activities for these two microalgae were affected by NPX at relatively high concentrations after 4d of exposure. Degradation of naproxen was accelerated by both algae species. Cymbella sp. showed a more satisfactive effect in the bioremediation of NPX with higher removal efficiency. A total of 12 metabolites were identified by LC-MS/MS and the degradation pathways of naproxen in two algae were proposed. Hydroxylation, decarboxylation, demethylation, tyrosine conjunction and glucuronidation contributed to naproxen transformation in algal cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. S-Naproxen and desmethylnaproxen glucuronidation by human liver microsomes and recombinant human UDP-glucuronosyltransferases (UGT): role of UGT2B7 in the elimination of naproxen

    PubMed Central

    Bowalgaha, Kushari; Elliot, David J; Mackenzie, Peter I; Knights, Kathleen M; Swedmark, Stellan; Miners, John O

    2005-01-01

    Aims To characterize the kinetics of S-naproxen (‘naproxen’) acyl glucuronidation and desmethylnaproxen acyl and phenolic glucuronidation by human liver microsomes and identify the human UGT isoform(s) catalysing these reactions. Methods Naproxen and desmethylnaproxen glucuronidation were investigated using microsomes from six and five livers, respectively. Human recombinant UGTs were screened for activity towards naproxen and desmethylnaproxen. Where significant activity was observed, kinetic parameters were determined. Naproxen and desmethylnaproxen glucuronides were measured by separate high-performance liquid chromatography methods. Results Naproxen acyl glucuronidation by human liver microsomes followed biphasic kinetics. Mean apparent Km values (±SD, with 95% confidence interval in parentheses) for the high- and low-affinity components were 29 ± 13 µm (16, 43) and 473 ± 108 µm (359, 587), respectively. UGT 1A1, 1A3, 1A6, 1A7, 1A8, 1A9, 1A10 and 2B7 glucuronidated naproxen. UGT2B7 exhibited an apparent Km (72 µm) of the same order as the high-affinity human liver microsomal activity, which was inhibited by the UGT2B7 selective ‘probe’ fluconazole. Although data for desmethylnaproxen phenolic glucuronidation by human liver microsomes were generally adequately fitted to either the single- or two-enzyme Michaelis–Menten equation, model fitting was inconclusive for desmethylnaproxen acyl glucuronidation. UGT 1A1, 1A7, 1A9 and 1A10 catalysed both the phenolic and acyl glucuronidation of desmethylnaproxen, while UGT 1A3, 1A6 and 2B7 formed only the acyl glucuronide. Atypical glucuronidation kinetics were variably observed for naproxen and desmethylnaproxen glucuronidation by the recombinant UGTs. Conclusion UGT2B7 is responsible for human hepatic naproxen acyl glucuronidation, which is the primary elimination pathway for this drug. PMID:16187975

  2. Factors influencing naproxen metabolite interference in total bilirubin assays.

    PubMed

    Saifee, Nabiha Huq; Ranjitkar, Pratistha; Greene, Dina N

    2016-04-01

    The factors influencing naproxen metabolite O-desmethylnaproxen (ODMN) positive interference in diazo-based Jendrassik and Grof (JG) total bilirubin (Tbil) assays and lack of interference in direct bilirubin (Dbil) assays have not been resolved. The objective of this study was to understand the conditions causing this interference pattern. Pooled normal and ultra-filtered plasma samples spiked with ODMN and naproxen were measured on the Beckman Coulter DxC and AU instruments. Absorbance spectra were obtained for ODMN mixed with Dbil reagent at original and adjusted pH. Absorbance spectra were also obtained for ODMN and bilirubin samples mixed with Tbil assay reagents. ODMN produces a positive interference in the DxC JG Tbil assays, but not the AU Tbil or Dbil assays or the DxC Dbil assay. Neutralizing the acidic pH of AU and DxC Dbil reagents allows ODMN to react with diazo salts. ODMN samples mixed with DxC and AU Tbil reagents produce broad peaks from 450 to 560nm and 400 to 540nm, respectively. The DxC JG Tbil assay monitors a change in absorbance at 520nm close to peak absorbance wavelength of diazo-reacted ODMN, whereas the AU Tbil assay monitors a change in absorbance at 570/660nm, beyond the peak absorbance wavelengths of diazo-reacted ODMN. The acidic pH of diazo-based Dbil assay reagents inhibits the reaction of ODMN with diazo salts. The AU JG Tbil assay is a reliable method to measure Tbil in the setting of naproxen overdose. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  3. Synergistic effect of the interaction between naproxen and citral on inflammation in rats.

    PubMed

    Ortiz, Mario I; González-García, Martha P; Ponce-Monter, Héctor A; Castañeda-Hernández, Gilberto; Aguilar-Robles, Paulina

    2010-12-15

    The combination of non-steroidal anti-inflammatory drugs with herbs having analgesic effects can increase their antinociceptive activity and limit their side effects. The aim of the present study was to examine the effects on inflammation and gastric injury in rats resulting from the interaction between naproxen and citral. Naproxen, citral, or fixed-dose naproxen-citral combinations were administered orally and their anti-inflammation (carrageenan-induced paw edema) and gastric damage were assessed in rats. The pharmacological interaction type was evaluated by the isobolographic analysis. Naproxen, citral, or combinations of naproxen and citral produced anti-inflammatory effects. The sole administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or combinations. ED(30) values were estimated for the individual drugs, and isobolograms were constructed. The derived theoretical ED(30) for the anti-inflammatory effect was 504.4 mg/kg; this was significantly higher than the observed experimental value (190.6 mg/kg). These results indicate that a synergistic interaction underlies the anti-inflammatory effect. The data suggests that the naproxen-citral combination can interact and to produce minor gastric damage and may have therapeutic advantages for the clinical treatment of inflammation. Copyright © 2010 Elsevier GmbH. All rights reserved.

  4. The combination of naproxen and citral reduces nociception and gastric damage in rats.

    PubMed

    Ortiz, Mario I; Ramírez-Montiel, Martha L; González-García, Martha P; Ponce-Monter, Héctor A; Castañeda-Hernández, Gilberto; Cariño-Cortés, Raquel

    2010-10-01

    It has been shown that the association of non-steroidal anti-inflammatory drugs with plant extracts can increase their antinociceptive activity, allowing the use of lower doses and, thus, limiting side effects. Therefore, the aim of this study was to examine the effects of the interaction between naproxen and citral on nociception and gastric injury in rats. Naproxen, citral, or combinations of naproxen and citral produced an antinociceptive effect. The administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or the naproxen-citral combination. The ED(50) value was estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED(50) for the antinociceptive effect (423.8 mg/kg) was not significantly different from the observed experimental value (359.0 mg/kg); hence, the interaction between naproxen and citral mediating the antinociceptive effect is additive. These data suggest that the naproxen-citral combination interacts at the systemic level, produces minor gastric damage, and potentially has therapeutic advantages for the clinical treatment of inflammatory pain.

  5. ¹H NMR-based metabolic profiling of naproxen-induced toxicity in rats.

    PubMed

    Jung, Jeeyoun; Park, Minhwa; Park, Hye Jin; Shim, Sun Bo; Cho, Yang Ha; Kim, Jinho; Lee, Ho-Sub; Ryu, Do Hyun; Choi, Donwoong; Hwang, Geum-Sook

    2011-01-15

    The dose-dependent perturbations in urinary metabolite concentrations caused by naproxen toxicity were investigated using ¹H NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic evaluation of naproxen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) of ¹H NMR from rat urine revealed a dose-dependent metabolic shift between the vehicle-treated control rats and rats treated with low-dose (10 mg/kg body weight), moderate-dose (50 mg/kg), and high-dose (100 mg/kg) naproxen, coinciding with their gastric damage scores after naproxen administration. The resultant metabolic profiles demonstrate that the naproxen-induced gastric damage exhibited energy metabolism perturbations that elevated their urinary levels of citrate, cis-aconitate, creatine, and creatine phosphate. In addition, naproxen administration decreased choline level and increased betaine level, indicating that it depleted the main protective constituent of the gastric mucosa. Moreover, naproxen stimulated the decomposition of tryptophan into kynurenate, which inhibits fibroblast growth factor-1 and delays ulcer healing. These findings demonstrate that ¹H NMR-based urinary metabolic profiling can facilitate noninvasive and rapid diagnosis of drug side effects and is suitable for elucidating possible biological pathways perturbed by drug toxicity. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Naproxen Interferes with the Assembly of Aβ Oligomers Implicated in Alzheimer's Disease

    PubMed Central

    Kim, Seongwon; Chang, Wenling E.; Kumar, Rashmi; Klimov, Dmitri K.

    2011-01-01

    Experimental and epidemiological studies have shown that the nonsteroidal antiinflammatory drug naproxen may be useful in the treatment of Alzheimer's disease. To investigate the interactions of naproxen with Aβ dimers, which are the smallest cytotoxic aggregated Aβ peptide species, we use united atom implicit solvent model and exhaustive replica exchange molecular dynamics. We show that naproxen ligands bind to Aβ dimer and penetrate its volume interfering with the interpeptide interactions. As a result naproxen induces a destabilizing effect on Aβ dimer. By comparing the free-energy landscapes of naproxen interactions with Aβ dimers and fibrils, we conclude that this ligand has stronger antiaggregation potential against Aβ fibrils rather than against dimers. The analysis of naproxen binding energetics shows that the location of ligand binding sites in Aβ dimer is dictated by the Aβ amino acid sequence. Comparison of the in silico findings with experimental observations reveals potential limitations of naproxen as an effective therapeutic agent in the treatment of Alzheimer's disease. PMID:21504739

  7. Structure-based design of novel naproxen derivatives targeting monomeric nucleoprotein of Influenza A virus

    PubMed Central

    Tarus, Bogdan; Bertrand, Hélène; Zedda, Gloria; Di Primo, Carmelo; Quideau, Stéphane; Slama-Schwok, Anny

    2015-01-01

    The nucleoprotein (NP) binds the viral RNA genome as oligomers assembled with the polymerase in a ribonucleoprotein complex required for transcription and replication of influenza A virus. Novel antiviral candidates targeting the nucleoprotein either induced higher order oligomers or reduced NP oligomerization by targeting the oligomerization loop and blocking its insertion into adjacent nucleoprotein subunit. In this study, we used a different structure-based approach to stabilize monomers of the nucleoprotein by drugs binding in its RNA-binding groove. We recently identified naproxen as a drug competing with RNA binding to NP with antiinflammatory and antiviral effects against influenza A virus. Here, we designed novel derivatives of naproxen by fragment extension for improved binding to NP. Molecular dynamics simulations suggested that among these derivatives, naproxen A and C0 were most promising. Their chemical synthesis is described. Both derivatives markedly stabilized NP monomer against thermal denaturation. Naproxen C0 bound tighter to NP than naproxen at a binding site predicted by MD simulations and shown by competition experiments using wt NP or single-point mutants as determined by surface plasmon resonance. MD simulations suggested that impeded oligomerization and stabilization of monomeric NP is likely to be achieved by drugs binding in the RNA grove and inducing close to their binding site conformational changes of key residues hosting the oligomerization loop as observed for the naproxen derivatives. Naproxen C0 is a potential antiviral candidate blocking influenza nucleoprotein function. PMID:25333630

  8. Structure-based design of novel naproxen derivatives targeting monomeric nucleoprotein of Influenza A virus.

    PubMed

    Tarus, Bogdan; Bertrand, Hélène; Zedda, Gloria; Di Primo, Carmelo; Quideau, Stéphane; Slama-Schwok, Anny

    2015-09-01

    The nucleoprotein (NP) binds the viral RNA genome as oligomers assembled with the polymerase in a ribonucleoprotein complex required for transcription and replication of influenza A virus. Novel antiviral candidates targeting the nucleoprotein either induced higher order oligomers or reduced NP oligomerization by targeting the oligomerization loop and blocking its insertion into adjacent nucleoprotein subunit. In this study, we used a different structure-based approach to stabilize monomers of the nucleoprotein by drugs binding in its RNA-binding groove. We recently identified naproxen as a drug competing with RNA binding to NP with antiinflammatory and antiviral effects against influenza A virus. Here, we designed novel derivatives of naproxen by fragment extension for improved binding to NP. Molecular dynamics simulations suggested that among these derivatives, naproxen A and C0 were most promising. Their chemical synthesis is described. Both derivatives markedly stabilized NP monomer against thermal denaturation. Naproxen C0 bound tighter to NP than naproxen at a binding site predicted by MD simulations and shown by competition experiments using wt NP or single-point mutants as determined by surface plasmon resonance. MD simulations suggested that impeded oligomerization and stabilization of monomeric NP is likely to be achieved by drugs binding in the RNA grove and inducing close to their binding site conformational changes of key residues hosting the oligomerization loop as observed for the naproxen derivatives. Naproxen C0 is a potential antiviral candidate blocking influenza nucleoprotein function.

  9. Structure and physicochemical characterization of a naproxen-picolinamide cocrystal.

    PubMed

    Kerr, Hannah E; Softley, Lorna K; Suresh, Kuthuru; Hodgkinson, Paul; Evans, Ivana Radosavljevic

    2017-03-01

    Naproxen (NPX) is a nonsteroidal anti-inflammatory drug with pain- and fever-relieving properties, currently marketed in the sodium salt form to overcome solubility problems; however, alternative solutions for improving its solubility across all pH values are desirable. NPX is suitable for cocrystal formation, with hydrogen-bonding possibilities via the COOH group. The crystal structure is presented of a 1:1 cocrystal of NPX with picolinamide as a coformer [systematic name: (S)-2-(6-methoxynaphthalen-2-yl)propanoic acid-pyridine-2-carboxamide (1/1), C 14 H 14 O 3 ·C 6 H 6 N 2 O]. The pharmaceutically relevant physical properties were investigated and the intrinsic dissolution rate was found to be essentially the same as that of commercial naproxen. An NMR crystallography approach was used to investigate the H-atom positions in the two crystallographically unique COOH-CONH hydrogen-bonded dimers. 1 H solid-state NMR distinguished the two carboxyl protons, despite the very similar crystallographic environments. The nature of the hydrogen bonding was confirmed by solid-state NMR and density functional theory calculations.

  10. Carbamazepine and naproxen: fate in wetland mesocosms planted with Scirpus validus.

    PubMed

    Zhang, Dong Qing; Hua, Tao; Gersberg, Richard M; Zhu, Junfei; Ng, Wun Jern; Tan, Soon Keat

    2013-03-01

    Scirpus validus was grown hydroponically and exposed to the pharmaceuticals, carbamazepine and naproxen at concentrations of 0.5-2.0 mg L(-1) for an exposure duration of up to 21 d. By the end of experiment, carbamazepine elimination from the nutrient solution reached to 74%, while nearly complete removal (>98%) was observed for naproxen. Photodegradation and biodegradation played only minor roles for carbamazepine elimination, while naproxen showed a high potential for both photodegradation and biodegradation. Levels of carbamazepine ranged from 3.3 to19.0 μg g(-1) (fresh weight) in the roots and 0.3-0.7 μg g(-1) (fresh weight) in the shoots, while naproxen concentrations were 0.2-2.4 μg g(-1) (fresh weight) in the roots and 0.2-2.8 μg g(-1) (fresh weight) in the shoots. Bioaccumulation factors (BAFs) for carbamazepine ranged from 5.5 to 13.0 for roots and 0.3-1.0 for shoots, and uptake by S. validus accounted for up to 22% of the total mass loss of carbamazepine in the nutrient solutions. All BAFs for naproxen were less than 4.2 and plant uptake accounted for less than 5% of the total mass loss of naproxen, implying that plant uptake was not significant in naproxen elimination. The rather limited plant uptake of naproxen was not surprising despite the fact that its log K(ow) is close to the optimal range (1.8-3.1) for maximal potential for plant uptake. Apparently, for ionizable compounds such as naproxen, the effects of pK(a) and pH partitioning might be more important than lipophilicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Naproxen-induced Ca2+ movement and death in MDCK canine renal tubular cells.

    PubMed

    Cheng, H-H; Chou, C-T; Sun, T-K; Liang, W-Z; Cheng, J-S; Chang, H-T; Tseng, H-W; Kuo, C-C; Chen, F-A; Kuo, D-H; Shieh, P; Jan, C-R

    2015-11-01

    Naproxen is an anti-inflammatory drug that affects cellular calcium ion (Ca(2+)) homeostasis and viability in different cells. This study explored the effect of naproxen on [Ca(2+)](i) and viability in Madin-Darby canine kidney cells (MDCK) canine renal tubular cells. At concentrations between 50 μM and 300 μM, naproxen induced [Ca(2+)](i) rises in a concentration-dependent manner. This Ca(2+) signal was reduced partly when extracellular Ca(2+) was removed. The Ca(2+) signal was inhibited by a Ca(2+) channel blocker nifedipine but not by store-operated Ca(2+) channel inhibitors (econazole and SKF96365), a protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, and a PKC inhibitor GF109203X. In Ca(2+)-free medium, pretreatment with 2,5-di-tert-butylhydroquinone or thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+) pumps, partly inhibited naproxen-induced Ca(2+) signal. Inhibition of phospholipase C with U73122 did not alter naproxen-evoked [Ca(2+)](i) rises. At concentrations between 15 μM and 30 μM, naproxen killed cells in a concentration-dependent manner, which was not reversed by prechelating cytosolic Ca(2+) with the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl. Annexin V/propidium iodide staining data suggest that naproxen induced apoptosis. Together, in MDCK renal tubular cells, naproxen induced [Ca(2+)](i) rises by inducing Ca(2+) release from multiple stores that included the endoplasmic reticulum and Ca(2+) entry via nifedipine-sensitive Ca(2+) channels. Naproxen induced cell death that involved apoptosis. © The Author(s) 2015.

  12. Intravenous lipid emulsion therapy in three cases of canine naproxen overdose.

    PubMed

    Herring, Jennifer M; McMichael, Maureen A; Corsi, Raffaella; Wurlod, Virginie

    2015-01-01

    To report a case series of canine naproxen overdoses successfully treated with intravenous lipid emulsion therapy (IVLE). Three dogs were presented for acute ingestion of naproxen and were treated with IVLE. Baseline and post treatment serum naproxen concentrations were measured. The first exposure involved ingestion of 61 mg/kg of an over-the-counter naproxen formulation in a 7-month-old male intact Labrador Retriever. Pre-IVLE toxin concentration assessed by high performance liquid chromatography (HPLC) was 73 μg/mL with a one-hour post-IVLE concentration decreasing to 30 μg/mL. The second and third exposures were 3-year-old female spayed Pembroke Welsh Corgi dogs from the same family, presented for potential ingestion of up to 207 mg/kg of a prescription strength naproxen formulation. Pre-IVLE naproxen concentration by HPLC for case 2 was 30 μg/mL with a reduction to 12 μg/mL and 7.2 μg/mL 1 and 3 hours post-IVLE treatment, respectively. For case 3, pre-IVLE naproxen concentration by HPLC was 86 μg/mL with post concentrations at 21 μg/mL one hour and 10 μg/mL 3 hours post-IVLE administration. Naproxen is a nonsteroidal anti-inflammatory drug with a long half-life and narrow margin of safety in dogs. Ingestion of > 5 mg/kg has been associated with adverse gastrointestinal effects, including ulceration. At doses > 10-25 mg/kg, acute kidney failure has been reported, and at doses > 50 mg/kg, neurologic abnormalities occur. This is the first reported use of IVLE for treatment of naproxen overdose with documented decrease in serum toxin concentrations shortly after administration. No long-standing gastrointestinal, renal, or neurologic effects occurred in these dogs. © Veterinary Emergency and Critical Care Society 2015.

  13. Don't Panic! Closed String Tachyons in ALE Spacetimes

    SciTech Connect

    Silverstein, Eva M

    2001-08-20

    We consider closed string tachyons localized at the fixed points of noncompact nonsupersymmetric orbifolds. We argue that tachyon condensation drives these orbifolds to flat space or supersymmetric ALE spaces. The decay proceeds via an expanding shell of dilaton gradients and curvature which interpolates between two regions of distinct angular geometry. The string coupling remains weak throughout. For small tachyon VEVs, evidence comes from quiver theories on D-branes probes, in which deformations by twisted couplings smoothly connect non-supersymmetric orbifolds to supersymmetric orbifolds of reduced order. For large tachyon VEVs, evidence comes from worldsheet RG flow and spacetime gravity. For C{sup 2}/Z{submore » n}, we exhibit infinite sequences of transitions producing SUSY ALE spaces via twisted closed string condensation from non-supersymmetric ALE spaces. In a T-dual description this provides a mechanism for creating NS5-branes via closed string tachyon condensation similar to the creation of D-branes via open string tachyon condensation. We also apply our results to recent duality conjectures involving fluxbranes and the type 0 string.« less

  14. Supra-Additive Interaction of Docosahexaenoic Acid and Naproxen and Gastric Safety on the Formalin Test in Rats.

    PubMed

    Arroyo-Lira, Arlette Guadalupe; Rodríguez-Ramos, Fernando; Ortiz, Mario I; Castañeda-Hernández, Gilberto; Chávez-Piña, Aracely Evangelina

    2017-11-01

    Preclinical Research The aim of this work was to evaluate the effect of docosahexaenoic acid (DHA) on the pharmacokinetics and pharmacodynamics-nociception-of naproxen in rats, as well as to determine the gastric safety resulting from this combination versus naproxen alone. Female Wistar rats were orally administered DHA, naproxen or the DHA-naproxen mixture at fixed-ratio combination of 1:3. The antinociceptive effect was evaluated using the formalin test. The gastric injury was determined 3 h after naproxen administration. An isobolographic analysis was performed to characterize the antinociceptive interaction between DHA and naproxen. To determine the possibility of pharmacokinetic interactions, the oral bioavailability of naproxen was evaluated in presence and absence of oral DHA. The experimental effective dose ED 30 values (Zexp) were decreased from theoretical additive dose values (Zadd; P < 0.05). The isobolographic analysis showed that the combination exhibited supra-additive interaction. The oral administration of DHA increased the pharmacokinetic parameter AUC 0- t of naproxen (P < 0.05). Furthermore, the gastric damage induced by naproxen was abolished when this drug was combined with DHA. These data suggest that oral administration of DHA-naproxen combination induces gastric safety and supra-additive antinociceptive effect in the formalin test so that this combination could be useful to management of inflammatory pain. Drug Dev Res 78 : 332-339, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Solubility of Naproxen in Polyethylene Glycol 200 + Water Mixtures at Various Temperatures

    PubMed Central

    Panahi-Azar, Vahid; Soltanpour, Shahla; Martinez, Fleming; Jouyban, Abolghasem

    2015-01-01

    The solubility of naproxen in binary mixtures of polyethylene glycol 200 (PEG 200) + water at the temperature range from 298.0 K to 318.0 K were reported. The combinations of Jouyban-Acree model + van’t Hoff and Jouyban-Acree model + partial solubility parameters were used to predict the solubility of naproxen in PEG 200 + water mixtures at different temperatures. Combination of Jouyban-Acree model with van’t Hoff equation can be used to predict solubility in PEG 200 + water with only four solubility data in mono-solvents. The obtained solubility calculation errors vary from ~ 17 % up to 35 % depend on the number of required input data. Non-linear enthalpy-entropy compensation was found for naproxen in the investigated solvent system and the Jouyban−Acree model provides reasonably accurate mathematical descriptions of the thermodynamic data of naproxen in the investigated binary solvent systems. PMID:26664370

  16. Amphiphilic naproxen prodrugs: differential scanning calorimetry study on their interaction with phospholipid bilayers.

    PubMed

    Giuffrida, Maria Chiara; Pignatello, Rosario; Castelli, Francesco; Sarpietro, Maria Grazia

    2017-09-01

    Naproxen, a nonsteroid anti-inflammatory drug studied for Alzheimer's disease, was conjugated with lipoamino acids (LAA) directly or through a diethylamine (EDA) spacer to improve the drug lipophilicity and the interaction with phospholipid bilayers. The interaction of naproxen and its prodrugs with biomembrane models consisting of dimyristoylphosphatidylcholine multilamellar vesicles was studied by differential scanning calorimetry. The transfer of prodrugs from a lipophilic carrier to a biomembrane model was also studied. Naproxen conjugation to lipoamino acids improves its interaction with biomembrane models and affects the transfer from a lipophilic carrier to biomembrane model. LAA portion may localize between the phospholipid chains; the entity of the interaction depends not only on the presence of the spacer but also on the LAA chain length. Variation of LAA portion can modulate the naproxen prodrugs affinity towards the biological membrane as well as towards the lipophilic carrier. © 2017 Royal Pharmaceutical Society.

  17. Synergism between Naproxen and Rutin in a Mouse Model of Visceral Pain.

    PubMed

    Alonso-Castro, Angel Josabad; Rangel-Velázquez, Joceline Estefanía; Isiordia-Espinoza, Mario A; Villanueva-Solís, Luis Enrique; Aragon-Martinez, Othoniel H; Zapata-Morales, Juan Ramón

    2017-08-01

    Preclinical Research The aim of the present study was to evaluate the antinociceptive interaction between naproxen and the glycoside flavonoid, rutin in the acetic acid-induced writhing test in mice. Naproxen (5, 20, 50, and 100 mg/kg p.o.) or rutin (10, 25, 50, and 100mg/kg p.o.) were administered 60 min before the intraperitoneal administration with acetic acid. The dose-response curve of each individual compound and the experimental effective dose 50 (ED 50 ) value were obtained to determinate different proportions of the combinations between the two compounds (naproxen-rutin 1:1, 3:1, and 3:1) in the writhing test. The results indicated a synergistic antinociceptive interaction between two drugs with different mechanism of action, naproxen and rutin in all the combinations. Drug Dev Res 78 : 184-188, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Biodegradation of micropollutant naproxen with a selected fungal strain and identification of metabolites.

    PubMed

    Aracagök, Y Doruk; Göker, Hakan; Cihangir, Nilüfer

    2017-05-01

    Pharmaceuticals are widely used for treating human and animal diseases. Naproxen [(S) 6-methoxy-α-methyl-2-naphthalene acetic acid] and its sodium salt are members of the α-arylpropionic acid group of nonsteroidal anti-inflammatory drugs. Due to excessive usage of naproxen, this drug has been determined even in drinking water. In this study, four fungal strains Phanerochaete chrysosporium, Funalia trogii, Aspergillus niger, and Yarrowia lipolytica were investigated in terms of naproxen removal abilities. According to LC/MS data, A. niger was found the most efficient strain with 98% removal rate. Two main by-products of fungal transformation, O-desmethylnaproxen and 7-hydroxynaproxen, were identified by using LC/MS, 1HNMR, and 13CNMR. Our results showed that O-demethylation and hydroxylation of naproxen is catalyzed by cytochrome P450 enzyme system.

  19. Comparison of ALE and SPH Methods for Simulating Mine Blast Effects on Structures

    DTIC Science & Technology

    2010-12-01

    Comparison of ALE and SPH methods for simulating mine blast effects on struc- tures Geneviève Toussaint Amal Bouamoul DRDC Valcartier Defence R&D...Canada – Valcartier Technical Report DRDC Valcartier TR 2010-326 December 2010 Comparison of ALE and SPH methods for simulating mine blast...Valcartier TR 2010-326 iii Executive summary Comparison of ALE and SPH methods for simulating mine blast effects on structures

  20. Toxicity of naproxen sodium and its mixture with tramadol hydrochloride on fish early life stages.

    PubMed

    Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Fiorino, Emma; Faggio, Caterina; Svobodova, Zdenka

    2017-12-01

    Pharmaceuticals occur in water bodies as a consequence of their incomplete removal during waste water treatment processes. The occurence of pharmaceuticals in surface waters as well as their possible impact on aquatic vertebrates have received considerable attention in recent years. However, there is still a lack of informations on the chronic effects of widely used drugs as well as their possible mixture toxicity on non-target aquatic vertebrates as well as their possible mixture toxicity. The aim of this study was to assess the effects of naproxen sodium on early life stages of fish and evaluate its mixture toxicity with tramadol hydrochloride, which was assessed in our earlier study as a single substance. Two embryo-larval toxicity tests with common carp (Cyprinus carpio) were performed according to the OECD guideline 210 (Fish, Early-life Stage Toxicity Test) in order to assess the subchronic toxicity of naproxen sodium and tramadol hydrochlorid-naproxen sodium mixture at the concentrations of 10; 50; 100 and 200 μg/L. These experiments were conducted for 32 days. The subchronic exposure to naproxen sodium and naproxen sodium and tramadol hydrochloride mixture had a strong effect on the early life stages of common carp. Hatching, developmental rate, morphology, histopathology and, in the case of the naproxen sodium and tramadol hydrochloride mixture, mortality were influenced. The bioindicators of oxidative stress were also influenced. The LOEC was determined at 10 μg/L for both naproxen sodium and naproxen sodium and tramadol hydrochloride mixture. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Isolation of (S)-(+)-naproxene from Musa acuminata. Inhibitory effect of naproxene and its 7-methoxy isomer on constitutive COX-1 and inducible COX-2.

    PubMed

    Abad, T; McNaughton-Smith, G; Fletcher, W Q; Echeverri, F; Diaz-Peñate, R; Tabraue, C; Ruiz de Galarreta, C M; López-Blanco, F; Luis, J G

    2000-06-01

    The isolation and characterisation of (S)-(+)-6-methoxy-alpha-methyl-2-naphthaleneacetic acid, a well known synthetic non-steroidal anti-inflammatory drug (naproxene), from a natural source is described for the first time. We evaluated the ability of naproxene and its 7-methoxy isomer to abrogate constitutive COX-1 and inducible COX-2 activity in human A549 cells. Naproxene inhibited COX-1 (IC50 = 3.42 microM) and COX-2 (IC50 = 1.53 microM), whereas the 7-methoxy isomer had no appreciable effect on COX-1 (IC50 > 100 microM) but also abrogated the activity of COX-2 enzyme (IC50 = 14.42 microM).

  2. Naproxen or estradiol for bleeding and spotting with the levonorgestrel intrauterine system: a randomized controlled trial.

    PubMed

    Madden, Tessa; Proehl, Sarah; Allsworth, Jenifer E; Secura, Gina M; Peipert, Jeffrey F

    2012-02-01

    The purpose of this study was to evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women who are initiating the levonorgestrel-releasing intrauterine system. We conducted a randomized controlled trial of naproxen, estradiol, or placebo that was administered over the first 12 weeks of levonorgestrel-releasing intrauterine system use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis. There were 129 women who were assigned randomly to naproxen (n = 42 women), estradiol (n = 44 women), or placebo (n = 43 women). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared with placebo (42.9% vs 16.3%; P = .03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (adjusted relative risk, 0.90; 95% confidence interval, 0.84-0.97) compared with placebo. More frequent bleeding and spotting was observed in the estradiol group (adjusted relative risk, 1.25; 95% confidence interval, 1.17-1.34). The administration of naproxen resulted in a reduction in bleeding and spotting days compared with placebo. Copyright © 2012 Mosby, Inc. All rights reserved.

  3. Structural studies of bovine, equine, and leporine serum albumin complexes with naproxen.

    PubMed

    Bujacz, Anna; Zielinski, Kamil; Sekula, Bartosz

    2014-09-01

    Serum albumin, a protein naturally abundant in blood plasma, shows remarkable ligand binding properties of numerous endogenous and exogenous compounds. Most of serum albumin binding sites are able to interact with more than one class of ligands. Determining the protein-ligand interactions among mammalian serum albumins is essential for understanding the complexity of this transporter. We present three crystal structures of serum albumins in complexes with naproxen (NPS): bovine (BSA-NPS), equine (ESA-NPS), and leporine (LSA-NPS) determined to 2.58 Å (C2), 2.42 Å (P61), and 2.73 Å (P2₁2₁2₁) resolutions, respectively. A comparison of the structurally investigated complexes with the analogous complex of human serum albumin (HSA-NPS) revealed surprising differences in the number and distribution of naproxen binding sites. Bovine and leporine serum albumins possess three NPS binding sites, but ESA has only two. All three complexes of albumins studied here have two common naproxen locations, but BSA and LSA differ in the third NPS binding site. None of these binding sites coincides with the naproxen location in the HSA-NPS complex, which was obtained in the presence of other ligands besides naproxen. Even small differences in sequences of serum albumins from various species, especially in the area of the binding pockets, influence the affinity and the binding mode of naproxen to this transport protein. © 2014 Wiley Periodicals, Inc.

  4. Naproxen or Estradiol for Bleeding and Spotting with the Levonorgestrel Intrauterine System: A Randomized Controlled Trial

    PubMed Central

    MADDEN, Tessa; PROEHL, Sarah; ALLSWORTH, Jenifer E.; SECURA, Gina M.; PEIPERT, Jeffrey F.

    2011-01-01

    Objective To evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women initiating the levonorgestrel-releasing intrauterine system (LNG-IUS). Study Design We conducted a randomized controlled trial of naproxen, estradiol, or placebo administered over the first 12 weeks of LNG-IUS use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis. Results There were 129 women randomized to naproxen (n=42), estradiol (n=44), or placebo (n=43). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared to placebo, 42.9% versus 16.3% (p=0.03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (RRadj 0.90, 95%CI 0.84–0.97) compared to placebo. More frequent bleeding and spotting was observed in the estradiol group (RRadj 1.25, 95%CI 1.17–1.34). Conclusions Administration of naproxen resulted in a reduction in bleeding and spotting days compared to placebo. (150 words) PMID:22055339

  5. The design of naproxen solid lipid nanoparticles to target skin layers.

    PubMed

    Akbari, Jafar; Saeedi, Majid; Morteza-Semnani, Katayoun; Rostamkalaei, Seyyed Sohrab; Asadi, Masoumeh; Asare-Addo, Kofi; Nokhodchi, Ali

    2016-09-01

    The aim of the current investigation was to produce naproxen solid lipid nanoparticles (Nap-SLNs) by the ultrasonication method to improve its skin permeation and also to investigate the influence of Hydrophilic-lipophilic balance (HLB) changes on nanoparticles properties. The properties of obtained SLNs loaded with naproxen were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). FT-IR was also used to investigate any interaction between naproxen and the excipients used at the molecular level during the preparation of the SLNs. The performance of the formulations was investigated in terms of skin permeation and also the retention of the drug by the skin. It was found that generally, with increasing the lipid concentration, the average particle size and polydispersity index (PDI) of SLNs increased from 94.257±4.852nm to 143.90±2.685nm and from 0.293±0.037 to 0.525±0.038 respectively. The results also showed that a reduction in the HLB resulted in an increase in the PDI, particle size, zeta potential and entrapment efficiency (EE%). DSC showed that the naproxen encapsulated in the SLNs was in its amorphous form. The peaks of prominent functional groups of naproxen were found in the FT-IR spectra of naproxen-SLN, which confirmed the entrapment of naproxen in the lipid matrix. FT-IR results also ruled out any chemical interaction between drug and the chemicals used in the preparation of SLNs. The amount of naproxen detected in the receptor chamber at all the sampling times for the reference formulation (naproxen solution containing all surfactants at pH 7.4) was higher than that of the Nap-SLN8 formulation. Nap-SLN8 showed an increase in the concentration of naproxen in the skin layer with less systemic absorption. This indicates that most of the drug in Nap-SLN8 remains in the skin which can reduce the side effect of systemic absorption of the drug and increases the

  6. NO-naproxen modulates inflammation, nociception and downregulates T cell response in rat Freund's adjuvant arthritis

    PubMed Central

    Cicala, Carla; Ianaro, Angela; Fiorucci, Stefano; Calignano, Antonio; Bucci, Mariarosaria; Gerli, Roberto; Santucci, Luca; Wallace, John L; Cirino, Giuseppe

    2000-01-01

    Anti-inflammatory non steroidal drugs releasing NO (NO-NSAIDs) are a new class of anti-inflammatory drugs to which has been added an NO-releasing moiety. These compounds have been shown to retain the anti-inflammatory, analgesic and antipyretic activity of the parent compound but to be devoid of gastrointestinal (GI) toxicity.Freund's adjuvant (FA) arthritis was induced in rats by a single intraplantar injection into the right hindpaw of 100 μl of mycobacterium butirricum (6 mg ml−1). The effect of equimolar doses of naproxen (1, 3 and 10 mg kg−1) and NO-naproxen (1.5, 4.5 and 16 mg kg−1) was evaluated using two dosage regimen protocols: (i) preventive, starting oral administration of the drugs at the time of induction of arthritis and for the following 21 days (day 1–21); (ii) therapeutic, starting oral administration of the drugs 7 days after adjuvant injection and for the following 14 days (day 7–21).Hindpaw swelling (days 3, 7, 11, 14, 17, 21) and nociception (days 15 and 21) were measured. On day 22 rats were sacrificed, draining lymph nodes were removed and T cells isolated. In vitro proliferation of T cells following stimulation with concanavalin A (0.5–5 μg ml−1) was measured using a tritiated thymidine incorporation assay. IL-2 receptor expression on T cells was measured by FACS analysis.Naproxen and NO-naproxen showed similar activity in reducing oedema formation in the non-injected (controlateral) hindpaw. Both drugs showed anti-nociceptive effect. NO-naproxen was anti-nociceptive at a dose of 4.5 mg kg−1 while naproxen showed the same extent of inhibition only at a dose of 10 mg kg−1.T cells were isolated and characterized by FACS analysis. Stimulation of isolated T cells with concanavallin A in vitro caused a significant increase in thymidine uptake. NO-naproxen at a dose of 4.5 mg kg−1 inhibited T cell proliferation to the same extent as 10 mg kg−1 of naproxen.Inhibition of T cell proliferation

  7. The ALE/GAGE/AGAGE Network (DB1001)

    DOE Data Explorer

    Prinn, Ronald G. [MIT, Center for Global Change Science; Weiss, Ray F. [University of California, San Diego; Scripps Institution of Oceanography; Krummel, Paul B. [CSIRO Oceans and Atmosphere, Cape Grim; O'Doherty, Simon [University of Bristol, Barbados and Mace Head Stations; Fraser, Paul [CSIRO Oceans and Atmosphere; Muhle, Jens [UCSD Scripps Institution of Oceanography; Cape Matatula Station; Reimann, Stefan [Swiss Federal Laboratories for Materials Science and Research (EMPA); Jungfraujoch Station; Vollmer, Martin [Swiss Federal Laboratories for Materials Science and Research (EMPA); Jungfraujoch Station; Simmonds, Peter G. [University of Bristol, Atmospheric Chemistry Research Group; Mace Head Station; Malone, Michela [University of Urbino; Monte Cimone Station; Arduini, Jgor [University of Urbino; Monte Cimone Station; Lunder, Chris [Norwegian Institute for Air Research; Ny Alesund Station; Hermansen, Ove [Norwegian Inst. for Air Research (NILU), Kjeller (Norway); Ny Alesund Station; Schmidbauer, Norbert [Norwegian Inst. for Air Research (NILU), Kjeller (Norway); Global Network; Young, Dickon [University of Bristol; Ragged Point Station; Wang, Hsiang J. (Ray) [Geogia Institute of Technology, School of Earth and Atmospheric Sciences; Global Network; Huang, Jin; Rigby, Matthew [University of Bristol; Global Network; Harth, Chris [UCSD, Scripps Institutioon of Oceanography; Global Network; Salameh, Peter [UCSD, Scripps Institution of Oceanography; Global Network; Spain, Gerard [National University of Ireland; Global Network; Steele, Paul [CSIRO Oceans and Atmosphere; Global Network; Arnold, Tim; Kim, Jooil [UCSD, Scripps Institution of Oceanography; Global Network; Derek, Nada; mitrevski, Blagoj; Langenfelds, Ray

    2008-01-01

    In the ALE/GAGE/AGAGE global network program, continuous high frequency gas chromatographic measurements of four biogenic/anthropogenic gases (methane, CH4; nitrous oxide, N2O; hydrogen, H; and carbon monoxide, CO) and several anthropogenic gases that contribute to stratospheric ozone destruction and/or to the greenhouse effect have been carried out at five globally distributed sites for several years. The program, which began in 1978, is divided into three parts associated with three changes in instrumentation: the Atmospheric Lifetime Experiment (ALE), which used Hewlett Packard HP5840 gas chromatographs; the Global Atmospheric Gases Experiment (GAGE), which used HP5880 gas chromatographs; and the present Advanced GAGE (AGAGE). AGAGE uses two types of instruments: a gas chromatograph with multiple detectors (GC-MD), and a gas chromatograph with mass spectrometric analysis (GC-MS). Beginning in January 2004, an improved cryogenic preconcentration system (Medusa) replaced the absorption-desorption module in the GC-MS systems at Mace Head and Cape Grim; this provided improved capability to measure a broader range of volatile perfluorocarbons with high global warming potentials. More information may be found at the AGAGE home page: http://agage.eas.gatech.edu/instruments-gcms-medusa.htm.

  8. A general higher-order remap algorithm for ALE calculations

    SciTech Connect

    Chiravalle, Vincent P

    2011-01-05

    A numerical technique for solving the equations of fluid dynamics with arbitrary mesh motion is presented. The three phases of the Arbitrary Lagrangian Eulerian (ALE) methodology are outlined: the Lagrangian phase, grid relaxation phase and remap phase. The Lagrangian phase follows a well known approach from the HEMP code; in addition the strain rate andflow divergence are calculated in a consistent manner according to Margolin. A donor cell method from the SALE code forms the basis of the remap step, but unlike SALE a higher order correction based on monotone gradients is also added to the remap. Four test problemsmore » were explored to evaluate the fidelity of these numerical techniques, as implemented in a simple test code, written in the C programming language, called Cercion. Novel cell-centered data structures are used in Cercion to reduce the complexity of the programming and maximize the efficiency of memory usage. The locations of the shock and contact discontinuity in the Riemann shock tube problem are well captured. Cercion demonstrates a high degree of symmetry when calculating the Sedov blast wave solution, with a peak density at the shock front that is similar to the value determined by the RAGE code. For a flyer plate test problem both Cercion and FLAG give virtually the same velocity temporal profile at the target-vacuum interface. When calculating a cylindrical implosion of a steel shell, Cercion and FLAG agree well and the Cercion results are insensitive to the use of ALE.« less

  9. Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation.

    PubMed

    Vistoli, G; De Maddis, D; Cipak, A; Zarkovic, N; Carini, M; Aldini, G

    2013-08-01

    Advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) have a pathogenetic role in the development and progression of different oxidative-based diseases including diabetes, atherosclerosis, and neurological disorders. AGEs and ALEs represent a quite complex class of compounds that are formed by different mechanisms, by heterogeneous precursors and that can be formed either exogenously or endogenously. There is a wide interest in AGEs and ALEs involving different aspects of research which are essentially focused on set-up and application of analytical strategies (1) to identify, characterize, and quantify AGEs and ALEs in different pathophysiological conditions; (2) to elucidate the molecular basis of their biological effects; and (3) to discover compounds able to inhibit AGEs/ALEs damaging effects not only as biological tools aimed at validating AGEs/ALEs as drug target, but also as promising drugs. All the above-mentioned research stages require a clear picture of the chemical formation of AGEs/ALEs but this is not simple, due to the complex and heterogeneous pathways, involving different precursors and mechanisms. In view of this intricate scenario, the aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation.

  10. Double-blind multicentre UK hospital studies of isoxicam vs naproxen

    PubMed Central

    Cardoe, N.; Hart, F. Dudley

    1986-01-01

    1 Two multicentre, parallel group, randomised, double-blind, double-dummy comparison studies were conducted between isoxicam in the usual dose of 200 mg once daily and naproxen 500 mg twice daily. 2 The drugs were administered for 4 weeks to 230 patients suffering from osteoarthritis of the hip and/or knee in the first trial and to 249 patients suffering from rheumatoid arthritis in the second. 3 The studies compared treatments for both safety and overall effectiveness in the relief of pain. 4 In the osteoarthritis trial, overall pain was reduced by both drugs after 2 weeks of therapy but only isoxicam produced further improvement after 4 weeks. 5 Isoxicam produced reductions comparable to those produced by naproxen in pain on standing from the sitting position, pain on walking, and pain on movement of the affected joint, after 2 and 4 weeks. 6 After 4 weeks, isoxicam given once daily in the morning was significantly more effective than naproxen given in the morning and the evening in relieving not only total pain as assessed by a visual analogue scale but, as importantly, night pain. 7 Compared to naproxen therapy, isoxicam therapy was associated with significantly more patients whose disease state was improved at 2 weeks, as assessed by physicians. 8 In the rheumatoid arthritis trial, isoxicam was equally as effective as naproxen in reducing joint tenderness, joint swelling, and pain; at 4 weeks there was a trend in favour of isoxicam in reduction of joint swelling and pain. 9 Isoxicam reduced morning stiffness significantly more than naproxen after 4 weeks; this trend was apparent at 2 weeks. 10 Patients thought that isoxicam was more effective than naproxen, to a significant difference. 11 In both trials, the two drugs were well tolerated and had similar side effects profiles, with the majority of adverse experiences being associated with the digestive system; no side effect was severe. PMID:3620277

  11. Fixed Drug Eruption Due to Selective Hypersensitivity to Naproxen with Tolerance to other Propionic Acid NSAIDs.

    PubMed

    Noguerado-Mellado, Blanca; Gamboa, Abdonias R; Perez-Ezquerra, Patricia R; Cabeza, Cristina M; Fernandez, Roberto P; De Barrio Fernandez, Manuel

    2016-01-01

    Naproxen is a non-steroidal anti-inflammatory drug (NSAID), belonging to propionic acid group, and its chemical structure is a 6-metoxi-metil-2-naftalenoacetic acid. Fixed drug eruptions (FDE) have been rarely reported. A 38-year-old woman referred that after 2 hours of taking 2 tablets of naproxen for a headache, she developed several edematous and dusky-red macules, one on right forearm and the other two in both thighs and she was diagnosed with FDE probably due to naproxen. We performed patch testing (PT) (Nonweven Patch Test Strips Curatest® Lohman & Rauscher International, Rangsdorf, Germany), with ibuprofen (5% Petrolatum), ketoprofen (2.5% Petrolatum), naproxen and nabumetone (both 10% in DMSO) on the residual lesion of the forearm with naproxen and in both thighs with ibuprofen, ketoprofen and nabumetone. Readings at day 1 (D1) and day 2 (D2) showed negative results to ibuprofen, ketoprofen and nabumetone, but were positive to naproxen in D1. A single blind oral challenge test (SBOCT) with other propionic acid derivates were performed in order to check for crossreactivity between them: ibuprofen, ketoprofen and nabumetone were administered and all drugs were well tolerated. In our patient PT confirmed the diagnosis and allowed us to study the cross-reactivity between NSAIDs of the same group, and confirmed by SBOCT. Cross-reactivity between propionic acid derivatives was studied. This is a case of hypersensitivity to naproxen with good tolerance to other propionic acids NSAIDs (ibuprofen and ketoprofen) and nabumetone, confirmed by PT and SBOCT. Some relavent patents for fixed drug eruption are discussed.

  12. Evaluation of the effect of naproxen on the pharmacokinetics and pharmacodynamics of apixaban

    PubMed Central

    Frost, Charles; Shenker, Andrew; Gandhi, Mohit D; Pursley, Janice; Barrett, Yu Chen; Wang, Jessie; Zhang, Donglu; Byon, Wonkyung; Boyd, Rebecca A; LaCreta, Frank

    2014-01-01

    Aim To assess pharmacokinetic and pharmacodynamic interactions between naproxen (a non-steroidal anti-inflammatory drug) and apixaban (an oral, selective, direct factor-Xa inhibitor). Method In this randomized, three period, two sequence study, 21 healthy subjects received a single oral dose of apixaban 10 mg, naproxen 500 mg or co-administration of both. Blood samples were collected for determination of apixaban and naproxen pharmacokinetics and pharmacodynamics (anti-Xa activity, international normalized ratio [INR] and arachidonic acid–induced platelet aggregation [AAI-PA]). Adverse events, bleeding time and routine safety assessments were also evaluated. Results Apixaban had no effect on naproxen pharmacokinetics. However, following co-administration, apixaban AUC(0,∞), AUC(0,t) and Cmax were 54% (geometric mean ratio 1.537; 90% confidence interval (CI) 1.394, 1.694), 55% (1.549; 90% CI 1.400, 1.713) and 61% (1.611; 90% CI 1.417, 1.831) higher, respectively. Mean (standard deviation [SD]) anti-Xa activity at 3 h post-dose was approximately 60% higher following co-administration compared with apixaban alone, 4.4 [1.0] vs. 2.7 [0.7] IU ml−1, consistent with the apixaban concentration increase following co-administration. INR was within the normal reference range after all treatments. AAI-PA was reduced by approximately 80% with naproxen. Co-administration had no impact beyond that of naproxen. Mean [SD] bleeding time was higher following co-administration (9.1 [4.1] min) compared with either agent alone (5.8 [2.3] and 6.9 [2.6] min for apixaban and naproxen, respectively). Conclusion Co-administration of naproxen with apixaban results in higher apixaban exposure and appears to occur through increased apixaban bioavailability. The effects on anti-Xa activity, INR and inhibition of AAI-PA observed in this study were consistent with the individual pharmacologic effects of apixaban and naproxen. PMID:24697979

  13. Effect of Aspirin Coadministration on the Safety of Celecoxib, Naproxen, or Ibuprofen.

    PubMed

    Reed, Grant W; Abdallah, Mouin S; Shao, Mingyuan; Wolski, Kathy; Wisniewski, Lisa; Yeomans, Neville; Lüscher, Thomas F; Borer, Jeffrey S; Graham, David Y; Husni, M Elaine; Solomon, Daniel H; Libby, Peter; Menon, Venu; Lincoff, A Michael; Nissen, Steven E

    2018-04-24

    The safety of nonsteroidal anti-inflammatory drug (NSAID) and aspirin coadministration is uncertain. The aim of this study was to compare the safety of combining NSAIDs with low-dose aspirin. This analysis of the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen) trial included 23,953 patients with osteoarthritis or rheumatoid arthritis at increased cardiovascular risk randomized to celecoxib, ibuprofen, or naproxen. The on-treatment population was used for this study. Outcomes included composite major adverse cardiovascular events, noncardiovascular death, gastrointestinal or renal events, and components of the composite. Cox proportional hazards models compared outcomes among NSAIDs stratified by aspirin use following propensity score adjustment. Kaplan-Meier analysis was used to compare the cumulative probability of events. When taken without aspirin, naproxen or ibuprofen had greater risk for the primary composite endpoint compared with celecoxib (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.22 to 1.90, p <0.001; and HR: 1.81; 95% CI: 1.46 to 2.26; p <0.001, respectively). Compared with celecoxib, ibuprofen had more major adverse cardiovascular events (p < 0.05), and both ibuprofen and naproxen had more gastrointestinal (p < 0.001) and renal (p < 0.05) events. Taken with aspirin, ibuprofen had greater risk for the primary composite endpoint compared with celecoxib (HR: 1.27; 95% CI: 1.06 to 1.51; p < 0.01); this was not significantly higher with naproxen (HR: 1.18; 95% CI: 0.98 to 1.41; p = 0.08). Among patients on aspirin, major adverse cardiovascular events were similar among NSAIDs, and compared with celecoxib, ibuprofen had more gastrointestinal and renal events (p < 0.05), while naproxen had more gastrointestinal events (p < 0.05), without a difference in renal events. Similar results were seen on adjusted Kaplan-Meier analysis. Celecoxib has a more favorable overall safety

  14. Evaluation of the effect of naproxen on the pharmacokinetics and pharmacodynamics of apixaban.

    PubMed

    Frost, Charles; Shenker, Andrew; Gandhi, Mohit D; Pursley, Janice; Barrett, Yu Chen; Wang, Jessie; Zhang, Donglu; Byon, Wonkyung; Boyd, Rebecca A; LaCreta, Frank

    2014-10-01

    To assess pharmacokinetic and pharmacodynamic interactions between naproxen (a non-steroidal anti-inflammatory drug) and apixaban (an oral, selective, direct factor-Xa inhibitor). In this randomized, three period, two sequence study, 21 healthy subjects received a single oral dose of apixaban 10 mg, naproxen 500 mg or co-administration of both. Blood samples were collected for determination of apixaban and naproxen pharmacokinetics and pharmacodynamics (anti-Xa activity, international normalized ratio [INR] and arachidonic acid-induced platelet aggregation [AAI-PA]). Adverse events, bleeding time and routine safety assessments were also evaluated. Apixaban had no effect on naproxen pharmacokinetics. However, following co-administration, apixaban AUC(0,∞), AUC(0,t) and Cmax were 54% (geometric mean ratio 1.537; 90% confidence interval (CI) 1.394, 1.694), 55% (1.549; 90% CI 1.400, 1.713) and 61% (1.611; 90% CI 1.417, 1.831) higher, respectively. Mean (standard deviation [SD]) anti-Xa activity at 3 h post-dose was approximately 60% higher following co-administration compared with apixaban alone, 4.4 [1.0] vs. 2.7 [0.7] IU ml(-1) , consistent with the apixaban concentration increase following co-administration. INR was within the normal reference range after all treatments. AAI-PA was reduced by approximately 80% with naproxen. Co-administration had no impact beyond that of naproxen. Mean [SD] bleeding time was higher following co-administration (9.1 [4.1] min) compared with either agent alone (5.8 [2.3] and 6.9 [2.6] min for apixaban and naproxen, respectively). Co-administration of naproxen with apixaban results in higher apixaban exposure and appears to occur through increased apixaban bioavailability. The effects on anti-Xa activity, INR and inhibition of AAI-PA observed in this study were consistent with the individual pharmacologic effects of apixaban and naproxen. © 2014 The British Pharmacological Society.

  15. Identification of Cytokines and Signaling Proteins Differentially Regulated by Sumatriptan/Naproxen

    PubMed Central

    Vause, Carrie V; Durham, Paul L

    2011-01-01

    Summary Objectives The goal of this study was to use protein array analysis to investigate temporal regulation of stimulated cytokine expression in trigeminal ganglia and spinal trigeminal nuclei in response to cotreatment of sumatriptan and naproxen sodium or individual drug. Background Activation of neurons and glia in trigeminal ganglia and spinal trigeminal nuclei leads to increased levels of cytokines that promote peripheral and central sensitization, which are key events in migraine pathology. While recent clinical studies have provided evidence that a combination of sumatriptan and naproxen sodium is more efficacious in treating migraine than either drug alone, it is not well understood why the combination therapy is superior to monotherapy. Methods Male Sprague Dawley rats were left untreated (control), injected with capsaicin, or pre-treated with sumatriptan/naproxen, sumatriptan, or naproxen for 1 hour prior to capsaicin. Trigeminal ganglia and spinal trigeminal nuclei were isolated 2 and 24 hours after capsaicin or drug treatment and levels of 90 proteins were determined using a RayBio® Label-Based Rat Antibody Array. Results Capsaicin stimulated a >3-fold increase in expression of the majority of cytokines in trigeminal ganglia at 2 hours that was sustained at 24 hours. Significantly, treatment with sumatriptan/naproxen almost completely abolished the stimulatory effects of capsaicin at 2 and 24 hours. Capsaicin stimulated >3-fold expression of more proteins in spinal trigeminal nuclei at 24 hours when compared to 2 hours. Similarly, sumatriptan/naproxen abolished capsaicin stimulation of proteins in spinal trigeminal nuclei at 2 hours and greatly suppressed protein expression 24 hours post capsaicin injection. Interestingly, treatment with sumatriptan alone suppressed expression of different cytokines in trigeminal ganglia and spinal trigeminal nuclei than repressed by naproxen sodium. Conclusion We found that the combination of sumatriptan/naproxen

  16. Photodegradation of naproxen and its photoproducts in aqueous solution at 254 nm: a kinetic investigation.

    PubMed

    Marotta, Raffaele; Spasiano, Danilo; Di Somma, Ilaria; Andreozzi, Roberto

    2013-01-01

    The kinetics of photodegradation of the non steroidal anti-inflammatory drug naproxen (+)-S-2-(6-methoxynaphthalen-2-yl)propanoic acid, an emerging organic pollutant, was studied in aqueous solutions under deaerated and aerated conditions. The photolysis experiments were carried out under monochromatic irradiation (λ = 254 nm) at pH = 7.0 and T = 25 °C. Simplified reaction schemes of photodegradation of naproxen are proposed in absence and in presence of oxygen respectively. The schemes take into account the photolysis of naproxen and its photoproducts and the reactions of the measured species with oxygen dissolved in the liquid bulk. According to these schemes, two kinetic models were developed which correlate the experimental data, for runs performed in absence and in presence of oxygen, with a fair accuracy and allowed to estimate the best values for the unknown kinetic parameters. The calculated quantum yield of direct photolysis of naproxen under deaerated media is in good agreement with the one previously reported. Under aerated conditions, the generation of singlet oxygen has also been taken into account. The obtained results, under the adopted conditions, indicated a marked influence of dissolved oxygen on the photodegradation rates of naproxen and the relative distribution of the major reaction intermediates. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Pharmacological Evaluation of Naproxen Metal Complexes on Antinociceptive, Anxiolytic, CNS Depressant, and Hypoglycemic Properties

    PubMed Central

    Das, Narhari; Abdur Rahman, S. M.

    2016-01-01

    Purpose. The present study was designed to investigate the antinociceptive, anxiolytic, CNS depressant, and hypoglycemic effects of the naproxen metal complexes. Methods. The antinociceptive activity was evaluated by acetic acid-induced writhing method and radiant heat tail-flick method while anxiolytic activity was evaluated by elevated plus maze model. The CNS depressant activity of naproxen metal complexes was assessed using phenobarbitone-induced sleeping time test and the hypoglycemic test was performed using oral glucose tolerance test. Results. Metal complexes significantly (P < 0.001) reduced the number of abdominal muscle contractions induced by 0.7% acetic acid solution in a dose dependent manner. At the dose of 25 mg/kg body weight p.o. copper, cobalt, and zinc complexes exhibited higher antinociceptive activity having 59.15%, 60.56%, and 57.75% of writhing inhibition, respectively, than the parent ligand naproxen (54.93%). In tail-flick test, at both doses of 25 and 50 mg/kg, the copper, cobalt, silver, and zinc complexes showed higher antinociceptive activity after 90 minutes than the parent drug naproxen. In elevated plus maze (EPM) model the cobalt and zinc complexes of naproxen showed significant anxiolytic effects in dose dependent manner, while the copper, cobalt, and zinc complexes showed significant CNS depressant and hypoglycemic activity. Conclusion. The present study demonstrated that copper, cobalt, and zinc complexes possess higher antinociceptive, anxiolytic, CNS depressant, and hypoglycemic properties than the parent ligand. PMID:27478435

  18. Effective anodic oxidation of naproxen by platinum nanoparticles coated FTO glass.

    PubMed

    Chin, Ching-Ju Monica; Chen, Tsan-Yao; Lee, Menshan; Chang, Chiung-Fen; Liu, Yu-Ting; Kuo, Yu-Tsun

    2014-07-30

    This study investigated applications of the electrochemical anodic oxidation process with Pt-FTO and Pt/MWCNTs-FTO glasses as anodes on the treatment of one of the most important emerging contaminants, naproxen. The anodes used in this study have been synthesized using commercial FTO, MWCNTs and Pt nanoparticles (PtNP). XRD patterns of Pt nanoparticles coated on FTO and MWCNTs revealed that MWCNTs can prevent the surface of PtNPs from sintering and thus provide a greater reaction sites density to interact with naproxen, which have also been confirmed by higher degradation and mineralization efficiencies in the Pt/MWCNTs-FTO system. Results from the CV analysis showed that the Pt-FTO and Pt/MWCNTs-FTO electrodes possessed dual functions of decreasing activation energy and interactions between hydroxyl radicals to effectively degrade naproxen. The lower the solution pH value, the better the degradation efficiency. The existence of humic acid indeed inhibited the degradation ability of naproxen due to the competitions in the multiple-component system. The electrochemical degradation processes were controlled by diffusion mechanism and two major intermediates of 2-acetyl-6-methoxynaphthalene and 2-(6-Hydroxy-2-naphthyl)propanoic acid were identified. This study has successfully demonstrated new, easy, flexible and effective anodic materials which can be feasibly applied to the electrochemical oxidation of naproxen. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Process parameter dependent growth phenomena of naproxen nanosuspension manufactured by wet media milling.

    PubMed

    Bitterlich, A; Laabs, C; Krautstrunk, I; Dengler, M; Juhnke, M; Grandeury, A; Bunjes, H; Kwade, A

    2015-05-01

    The production of nanosuspensions has proved to be an effective method for overcoming bioavailability challenges of poorly water soluble drugs. Wet milling in stirred media mills and planetary ball mills has become an established top-down-method for producing such drug nanosuspensions. The quality of the resulting nanosuspension is determined by the stability against agglomeration on the one hand, and the process parameters of the mill on the other hand. In order to understand the occurring dependencies, a detailed screening study, not only on adequate stabilizers, but also on their optimum concentration was carried out for the active pharmaceutical ingredient (API) naproxen in a planetary ball mill. The type and concentration of the stabilizer had a pronounced influence on the minimum particle size obtained. With the best formulation the influence of the relevant process parameters on product quality was investigated to determine the grinding limit of naproxen. Besides the well known phenomenon of particle agglomeration, actual naproxen crystal growth and morphology alterations occurred during the process which has not been observed before. It was shown that, by adjusting the process parameters, those effects could be reduced or eliminated. Thus, besides real grinding and agglomeration a process parameter dependent ripening of the naproxen particles was identified to be a concurrent effect during the naproxen fine grinding process. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Naproxen conjugated mPEG-PCL micelles for dual triggered drug delivery.

    PubMed

    Karami, Zahra; Sadighian, Somayeh; Rostamizadeh, Kobra; Parsa, Maliheh; Rezaee, Saeed

    2016-04-01

    A conjugate of the NSAIDs drug, naproxen, with diblock methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) copolymer was synthesized by the reaction of copolymer with naproxen in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The naproxen conjugated copolymers were characterized with different techniques including (1)HNMR, FTIR, and DSC. The naproxen conjugated mPEG-PCL copolymers were self-assembled into micelles in aqueous solution. The TEM analysis revealed that the micelles had the average size of about 80 nm. The release behavior of conjugated copolymer was investigated in two different media with the pH values of 7.4 and 5.2. In vitro release study showed that the drug release rate was dependant on pH as it was higher at lower pH compared to neutral pH. Another feature of the conjugated micelles was a more sustained release profile compared to the conjugated copolymer. The kinetic of the drug release from naproxen conjugated micelles under different values of pH was also investigated by different kinetic models such as first-order, Makoid-Banakar, Weibull, Logistic, and Gompertz. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Comparison of rectal indomethacin, diclofenac, and naproxen for the prevention of post endoscopic retrograde cholangiopancreatography pancreatitis.

    PubMed

    Mohammad Alizadeh, Amir H; Abbasinazari, Mohammad; Hatami, Behzad; Abdi, Saeed; Ahmadpour, Forozan; Dabir, Shideh; Nematollahi, Aida; Fatehi, Samira; Pourhoseingholi, Mohammad A

    2017-03-01

    NSAIDs are commonly utilized for the prevention of post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). However, not much is known about the most effective drug in preventing this complication. This study aims to clarify which drug (indomethacin, diclofenac, or naproxen) is most effective for the prevention of post endoscopic retrograde cholangiopancreatography (ERCP). In a double-blind, randomized study, patients received a single rectal dose of one of the three drugs 30 min before undergoing ERCP: diclofenac (100 mg), indomethacin (100 mg), or naproxen (500 mg). The primary outcome measured was the development of pancreatitis. The levels of serum amylase, lipase, lipoxin A4, and resolvin E1 were measured before ERCP, and at 24 h after the procedure. Three hundred and seventy-two patients completed the study. The overall incidence of PEP was 8.6%, which occurred in five of the 124 (4%) patients who received diclofenac, seven of the 122 (5.8%) patients who received indomethacin, and 20 of the 126 (15.9%) patients who received naproxen. There were no significant differences in amylase and lipase levels among the three groups (P=0.183 and 0.597, respectively). Unlike patients in the naproxen group, patients in the diclofenac and indomethacin groups showed a significant increase in lipoxin A4 and resolvin E1 (P=0.001 and 0.02, respectively). Diclofenac and indomethacin patient groups had a lower incidence of PEP than the naproxen group.

  2. Synergistic Skin Penetration Enhancer and Nanoemulsion Formulations Promote the Human Epidermal Permeation of Caffeine and Naproxen.

    PubMed

    Abd, Eman; Namjoshi, Sarika; Mohammed, Yousuf H; Roberts, Michael S; Grice, Jeffrey E

    2016-01-01

    We examined the extent of skin permeation enhancement of the hydrophilic drug caffeine and lipophilic drug naproxen applied in nanoemulsions incorporating skin penetration enhancers. Infinite doses of fully characterized oil-in-water nanoemulsions containing the skin penetration enhancers oleic acid or eucalyptol as oil phases and caffeine (3%) or naproxen (2%) were applied to human epidermal membranes in Franz diffusion cells, along with aqueous control solutions. Caffeine and naproxen fluxes were determined over 8 h. Solute solubility in the formulations and in the stratum corneum (SC), as well as the uptake of product components into the SC were measured. The nanoemulsions significantly enhanced the skin penetration of caffeine and naproxen, compared to aqueous control solutions. Caffeine maximum flux enhancement was associated with a synergistic increase in both caffeine SC solubility and skin diffusivity, whereas a formulation-increased solubility in the SC was the dominant determinant for increased naproxen fluxes. Enhancements in SC solubility were related to the uptake of the formulation excipients containing the active compounds into the SC. Enhanced skin penetration in these systems is largely driven by uptake of formulation excipients containing the active compounds into the SC with impacts on SC solubility and diffusivity.

  3. Flow injection chemiluminescence determination of loxoprofen and naproxen with the acidic permanganate-sulfite system

    PubMed Central

    Wang, Li-Juan; Tang, Yu-Hai; Liu, Yang-Hao

    2012-01-01

    A novel flow injection chemiluminescence (CL) method for the determination of loxoprofen and naproxen was proposed based on the CL system of KMnO4, and Na2SO3 in acid media. The CL intensity of KMnO4-Na2SO3 was greatly enhaneed in the presence of loxoprofen and naproxen. The mechanism of the CL reaction was studied by the kinetic proecss and UV-vis absorption and the conditions were optimized. Under optimized conditions, the CL intensity was linear with loxoprofen and naproxen concentration in the range of 7.0 × 10−8 – 1.0 × 10−5 g/mL and 2.0 × 10−7 – 4.0 × 10−6 g/mL with the detection limit of 2.0 × 10−8 g/mL and 3.0 × 10−8 g/mL (S/N = 3), respectively. Thc relative standard deviations were 2.39% and 1.37% for 5.0 × 10−7 g/mL naproxen and 5.0 × 10−7 g/mL loxoprofen (n = 10), respectively. The proposed method was satisfactorily applied to thc determination of loxoprofen and naproxen in pharmaceutical preparations. PMID:29403682

  4. Flow injection chemiluminescence determination of loxoprofen and naproxen with the acidic permanganate-sulfite system.

    PubMed

    Wang, Li-Juan; Tang, Yu-Hai; Liu, Yang-Hao

    2011-02-01

    A novel flow injection chemiluminescence (CL) method for the determination of loxoprofen and naproxen was proposed based on the CL system of KMnO 4 , and Na 2 SO 3 in acid media. The CL intensity of KMnO 4 -Na 2 SO 3 was greatly enhaneed in the presence of loxoprofen and naproxen. The mechanism of the CL reaction was studied by the kinetic proecss and UV-vis absorption and the conditions were optimized. Under optimized conditions, the CL intensity was linear with loxoprofen and naproxen concentration in the range of 7.0 × 10 -8 - 1.0 × 10 -5 g/mL and 2.0 × 10 -7 - 4.0 × 10 -6 g/mL with the detection limit of 2.0 × 10 -8 g/mL and 3.0 × 10 -8 g/mL (S/N = 3), respectively. Thc relative standard deviations were 2.39% and 1.37% for 5.0 × 10 -7 g/mL naproxen and 5.0 × 10 -7 g/mL loxoprofen ( n = 10), respectively. The proposed method was satisfactorily applied to thc determination of loxoprofen and naproxen in pharmaceutical preparations.

  5. The Montana ALE (Autonomous Lunar Excavator) Systems Engineering Report

    NASA Technical Reports Server (NTRS)

    Hull, Bethanne J.

    2012-01-01

    On May 2 1-26, 20 12, the third annual NASA Lunabotics Mining Competition will be held at the Kennedy Space Center in Florida. This event brings together student teams from universities around the world to compete in an engineering challenge. Each team must design, build and operate a robotic excavator that can collect artificial lunar soil and deposit it at a target location. Montana State University, Bozeman, is one of the institutions selected to field a team this year. This paper will summarize the goals of MSU's lunar excavator project, known as the Autonomous Lunar Explorer (ALE), along with the engineering process that the MSU team is using to fulfill these goals, according to NASA's systems engineering guidelines.

  6. Fourth-order derivative spectrophotometric method for simultaneous determination of pseudoephedrine and naproxen in pharmaceutical dosage forms

    PubMed Central

    Souri, Effat; Mosafer, Amir; Tehrani, Maliheh Barazandeh

    2016-01-01

    Combination dosage forms of naproxen sodium and pseudoephedrine hydrochloride are used for symptomatic treatment of cold and sinus disorders. In this study, fourth-order derivative spectrophotometric method was used for simultaneous determination of naproxen sodium and pseudoephedrine hydrochloride. The method was linear over the range of 2-28 μg/ml for pseudoephedrine hydrochloride and 4-200 μg/ml for naproxen sodium. The within-day and between-day coefficient of variation values were less than 5.8% and 2.5% for pseudoephedrine hydrochloride and naproxen sodium, respectively. The application of the proposed method for simultaneous determination of naproxen and pseudoephedrine in dosage forms was demonstrated without any special pretreatment. PMID:27168748

  7. Simulation of underwater explosion benchmark experiments with ALE3D

    SciTech Connect

    Couch, R.; Faux, D.

    1997-05-19

    Some code improvements have been made during the course of this study. One immediately obvious need was for more flexibility in the constitutive representation for materials in shell elements. To remedy this situation, a model with a tabular representation of stress versus strain and rate dependent effects was implemented. This was required in order to obtain reasonable results in the IED cylinder simulation. Another deficiency was in the ability to extract and plot variables associated with shell elements. The pipe whip analysis required the development of a scheme to tally and plot time dependent shell quantities such as stresses andmore » strains. This capability had previously existed only for solid elements. Work was initiated to provide the same range of plotting capability for structural elements that exist with the DYNA3D/TAURUS tools. One of the characteristics of these problems is the disparity in zoning required in the vicinity of the charge and bubble compared to that needed in the far field. This disparity can cause the equipotential relaxation logic to provide a less than optimal solution. Various approaches were utilized to bias the relaxation to obtain more optimal meshing during relaxation. Extensions of these techniques have been developed to provide more powerful options, but more work still needs to be done. The results presented here are representative of what can be produced with an ALE code structured like ALE3D. They are not necessarily the best results that could have been obtained. More experience in assessing sensitivities to meshing and boundary conditions would be very useful. A number of code deficiencies discovered in the course of this work have been corrected and are available for any future investigations.« less

  8. Gastric-sparing nitric oxide-releasable 'true' prodrugs of aspirin and naproxen.

    PubMed

    Gund, Machhindra; Gaikwad, Parikshit; Borhade, Namdev; Burhan, Aslam; Desai, Dattatraya C; Sharma, Ankur; Dhiman, Mini; Patil, Mohan; Sheikh, Javed; Thakre, Gajanan; Tipparam, Santhosh G; Sharma, Somesh; Nemmani, Kumar V S; Satyam, Apparao

    2014-12-15

    Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as potentially gastric-sparing NSAIDs. Herein, we report a novel class of '1-(nitrooxy)ethyl ester' group-containing NSAIDS as efficient NO releasing 'true' prodrugs of aspirin and naproxen. While an aspirin prodrug exhibited comparable oral bioavailability and antiplatelet activity (i.e., TXB2 inhibition) to those of aspirin, a naproxen prodrug exhibited better bioavailability than naproxen. These promising NO-NSAIDs protected experimental rats from gastric damage. We therefore believe that these promising NO-NSAIDs could represent a new class of potentially 'Safe NSAIDs' for the treatment of arthritic pain, inflammation and cardiovascular disorders in the case of NO-aspirin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Characterization of naproxen-loaded solid SMEDDSs prepared by spray drying: the effect of the polysaccharide carrier and naproxen concentration.

    PubMed

    Čerpnjak, Katja; Zvonar, Alenka; Vrečer, Franc; Gašperlin, Mirjana

    2015-05-15

    The purpose of this study was to prepare solid SMEDDS (sSMEDDS) particles produced by spray-drying using maltodextrin (MD), hypromellose (HPMC), and a combination of the two as a solid carrier. Naproxen (NPX) as the model drug was dissolved (at 6% concentration) or partially suspended (at 18% concentration) in a liquid SMEDDS composed of Miglyol(®) 812, Peceol™, Gelucire(®) 44/14, and Solutol(®) HS 15. Among the sSMEDDSs tested, the MD-based sSMEDDSs (with a granular, smooth-surfaced, microspherical appearance) preserved the self-microemulsifying properties of liquid SMEDDSs and exhibited dissolution profiles similar to those of liquid SMEDDSs, irrespective of the concentration of NPX. In contrast, HPMC-based sSMEDDSs (irregular-shaped microparticles) exhibited slightly prolonged release times due to the polymeric nature of the carrier. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and Raman mapping analysis confirmed molecularly dissolved NPX (at 6% of drug loading), whereas at 18% NPX loading drug is partially molecularly dissolved and partially in the crystalline state. Copyright © 2015. Published by Elsevier B.V.

  10. Nonselective inhibition of prostaglandin-endoperoxide synthase by naproxen ameliorates hepatic injury in animals with acute or chronic liver injury

    PubMed Central

    Bahde, Ralf; Kapoor, Sorabh; Gupta, Sanjeev

    2014-01-01

    The rising prevalence of hepatic injury due to toxins, metabolites, viruses, etc., necessitates development of further mechanisms for protecting the liver and for treating acute or chronic liver diseases. To examine whether inhibition of inflammation directed by cyclo-oxygenase pathways, we performed animal studies with naproxen, which inhibits prostaglandin-endoperoxide synthases 1 and 2 and is in extensive clinical use. We administered carbon tetrachloride to induce acute liver injury and ligated the common bile duct to induce chronic liver injury in adult rats. These experimental manipulations produced abnormalities in liver tests, tissue necrosis, compensatory hepatocyte or biliary proliferation, and onset of fibrosis, particularly after bile duct ligation. After carbon tetrachloride-induced acute injury, naproxen decreased liver test abnormalities, tissue necrosis and compensatory hepatocellular proliferation. After bile duct ligation-induced chronic injury, naproxen decreased liver test abnormalities, tissue injury and compensatory biliary hyperplasia. Moreover, after bile duct ligation, naproxen-treated rats showed more periductular oval liver cells, which have been classified as hepatic progenitor cells. In naproxen-treated rats, we found greater expression in hepatic stellate cells and mononuclear cells of cytoprotective factors, such as vascular endothelial growth factor. The ability of naproxen to induce expression of vascular endothelial growth factor was verified in cell culture studies with CFSC-8B clone of rat hepatic stellate cells. Whereas assays for carbon tetrachloride toxicity using cultured primary hepatocytes established that naproxen was not directly cytoprotective, we found conditioned medium containing vascular endothelial growth factor from naproxen-treated CFSC-8B cells protected hepatocytes from carbon tetrachloride toxicity. Therefore, naproxen was capable of ameliorating toxic liver injury, which involved naproxen-induced release of

  11. Sorption of the pharmaceuticals carbamazepine and naproxen to dissolved organic matter: role of structural fractions.

    PubMed

    Maoz, Adi; Chefetz, Benny

    2010-02-01

    Pharmaceutical compounds and dissolved organic matter (DOM) are co-introduced into the environment by irrigation with reclaimed wastewater and/or application of biosolids. In this study, we evaluate the role and mechanism of interaction of the pharmaceuticals naproxen and carbamazepine with structural fractions of biosolids-derived DOM. Sorption interactions were estimated from dialysis-bag experiments at different pHs. Sorption of naproxen and carbamazepine by the hydrophobic acid fraction exhibited strong pH-dependence. With both pharmaceuticals, the highest sorption coefficients (K(DOC)) were at pH 4. With the hydrophobic neutral fraction, pH affected only naproxen sorption (decreasing with increasing pH). Among the hydrophilic DOM fractions, the hydrophilic acid fraction exhibited the highest K(DOC) value for carbamazepine, probably due to their bipolar character. In the hydrophilic acid fraction-naproxen system, significant anionic repulsion was observed with increasing pH. The hydrophilic base fraction contains positively charged functional groups. Therefore with increasing ionization of naproxen (with increasing pH), K(DOC) to this fraction increased. The hydrophilic neutral fraction exhibited the lowest K(DOC) with both studied pharmaceuticals. The K(DOC) value of carbamazepine with the bulk DOM sample was higher than the calculated K(DOC) value based on sorption by the individual isolated fractions. The opposite trend was observed with naproxen at pH 8: the calculated K(DOC) value was higher than the value obtained for the bulk DOM. These results demonstrate that DOM fractions interact with each other and do not act as separate sorption domains. (c) 2009 Elsevier Ltd. All rights reserved.

  12. Development of Self Emulsifying Formulations of Poorly Soluble Naproxen for Enhanced Drug Delivery.

    PubMed

    Penjuri, Subhash C B; Saritha, Damineni; Ravouru, Nagaraju; Poreddy, Srikanth R

    2016-01-01

    The objective of this investigation was to develop a self emulsifying drug delivery system (SEDDS) of naproxen, a poorly water soluble drug, which could improve its solubility and oral bioavailability. The recent patents on SEDDS of abiraterone acetate (WO2014/009434 A1) and tamoxifen (WO2013/0080083) helped in selecting the naproxen and excipients. Phase diagrams were constructed and the formulations were taken from the micro emulsion region. Formulations were subjected to thermodynamic stability, dispersibility and precipitation tests for optimization. Physico chemical characterization was carried out by FTIR and DSC studies. The selected SEDDS consisted of IPM+labrafac lipophile WL 1349, tween 80, PEG 400 and naproxen. The optimized formulation has globule size- 187.6 nm, zeta potential- -9.81 mv, viscosity- 1.772 cps and infinite dilution ability. In vitro drug release was 98.21% and was found to be significantly different from the marketed product and plain drug. After oral administration in rats the SEDDS of naproxen showed anti inflammatory activity (69.82%) which was much improved as compared to the marketed formulation. The Cmax, AUC0t of naproxen was boosted with SEDDS to 133.63 g/ml and 698.29 hr. g/ml respectively. The optimized formulation was found to be stable for 6 months during stability studies conducted according to the ICH Q1A (R2) guidelines. Thus this developed self emulsifying drug delivery system may be a useful tool to enhance the solubility of oral poorly water soluble drug naproxen. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Simulating Small-Scale Experiments of In-Tunnel Airblast Using STUN and ALE3D

    SciTech Connect

    Neuscamman, Stephanie; Glenn, Lewis; Schebler, Gregory

    2011-09-12

    This report details continuing validation efforts for the Sphere and Tunnel (STUN) and ALE3D codes. STUN has been validated previously for blast propagation through tunnels using several sets of experimental data with varying charge sizes and tunnel configurations, including the MARVEL nuclear driven shock tube experiment (Glenn, 2001). The DHS-funded STUNTool version is compared to experimental data and the LLNL ALE3D hydrocode. In this particular study, we compare the performance of the STUN and ALE3D codes in modeling an in-tunnel airblast to experimental results obtained by Lunderman and Ohrt in a series of small-scale high explosive experiments (1997).

  14. ALE3D: An Arbitrary Lagrangian-Eulerian Multi-Physics Code

    SciTech Connect

    Noble, Charles R.; Anderson, Andrew T.; Barton, Nathan R.

    ALE3D is a multi-physics numerical simulation software tool utilizing arbitrary-Lagrangian- Eulerian (ALE) techniques. The code is written to address both two-dimensional (2D plane and axisymmetric) and three-dimensional (3D) physics and engineering problems using a hybrid finite element and finite volume formulation to model fluid and elastic-plastic response of materials on an unstructured grid. As shown in Figure 1, ALE3D is a single code that integrates many physical phenomena.

  15. Elucidation of the naproxen sodium adsorption onto activated carbon prepared from waste apricot: kinetic, equilibrium and thermodynamic characterization.

    PubMed

    Onal, Y; Akmil-Başar, C; Sarici-Ozdemir, C

    2007-09-30

    In this study, activated carbon (WA11Zn5) was prepared from waste apricot, which is waste in apricot plants in Malatya, by chemical activation with ZnCl(2). BET surface area of activated carbon is determined as 1060 m(2)/g. The ability of WA11Zn5, to remove naproxen sodium from effluent solutions by adsorption has been studied. Equilibrium isotherms for the adsorption of naproxen sodium on activated carbon were measured experimentally. Results were analyzed by the Langmiur, Freundlich equation using linearized correlation coefficient at 298 K. The characteristic parameters for each isotherm have been determined. Langmiur equation is found to best represent the equilibrium data for naproxen sodium-WA11Zn5 systems. The monolayer adsorption capacity of WA11Zn5 for naproxen sodium was found to be 106.38 mg/g at 298 K. The process was favorable and spontaneous. The kinetics of adsorption of naproxen sodium have been discussed using three kinetic models, i.e., the pseudo first-order model, the pseudo second-order model, the intraparticle diffusion model. Kinetic parameters and correlation coefficients were determined. It was shown that the pseudo second-order kinetic equation could describe the adsorption kinetics for naproxen sodium onto WA11Zn5. The thermodynamic parameters, such as DeltaG degrees , DeltaS degrees and DeltaH degrees, were calculated. The thermodynamics of naproxen sodium-WA11Zn5 system indicates endothermic process.

  16. Enteric protection of naproxen in a fixed-dose combination product produced by hot-melt co-extrusion.

    PubMed

    Vynckier, A-K; De Beer, M; Monteyne, T; Voorspoels, J; De Beer, T; Remon, J P; Vervaet, C

    2015-08-01

    In this study hot-melt co-extrusion is used as processing technique to manufacture a fixed-dose combination product providing enteric protection to naproxen incorporated in the core and immediate release to esomeprazole magnesium embedded in the coat. The plasticizing effect of naproxen and triethyl citrate (TEC) was tested on the enteric polymers investigated (Eudragit(®) L100-55, HPMC-AS-LF and HPMCP-HP-50). Core matrix formulations containing HPMC-AS-LF, TEC and a naproxen load of 15, 30 and 50% were processed and characterized. The in vitro naproxen release in 0.1N HCl was prevented for 2h for all formulations. The physicochemical state of the drug in the extrudates was determined and a stability study was performed. Intermolecular interactions between naproxen and polymer were identified using attenuated total reflection Fourier-transform infrared (ATR FT-IR) spectroscopy. When esomeprazole magnesium was formulated in a polyethylene oxide 100K:polyethylene glycol 4K (1:1) matrix, separated from the naproxen-containing layer, the formulation could be easily processed and complete in vitro drug release was observed after 45 min. When co-extruding the core/coat dosage form it was observed that a third layer of polymer, separating the naproxen loaded enteric formulation in the core from the coat, is required to prevent degradation of the acid-labile esomeprazole magnesium at the core/coat interface. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Removal of naproxen and bezafibrate by activated sludge under aerobic conditions: kinetics and effect of substrates.

    PubMed

    Tang, Ying; Li, Xiao-Ming; Xu, Zhen-Cheng; Guo, Qing-Wei; Hong, Cheng-Yang; Bing, Yong-Xin

    2014-01-01

    Naproxen and bezafibrate fall into the category of pharmaceuticals that have been widely detected in the aquatic environment, and one of the major sources is the effluent discharge from wastewater treatment plants. This study investigated the sorption and degradation kinetics of naproxen and bezafibrate in the presence of activated sludge under aerobic conditions. Experimental results indicated that the adsorption of pharmaceuticals by activated sludge was rapid, and the relative adsorbabilities of the two-target compounds were based on their log Kow and pKa values. The adsorption data could be well interpreted by the pseudo-second-order kinetic model. The degradation process could be described by the pseudo-first-order kinetic model, whereas the pseudo-second-order kinetics were also well suited to describe the degradation process of the selected compounds at low concentrations. Bezafibrate was more easily degraded by activated sludge compared with naproxen. The spiked concentration of the two-target compounds was negatively correlated with k1 and k2s , indicating that the substrate inhibition effect occurred at the range of studied concentrations. Chemical oxygen demand (COD) did not associate with naproxen degradation; thus, COD is not an alternative method that could be applied to investigate natural organic matter's impact on degradation of pharmaceuticals by activated sludge. © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  18. Features of the adsorption of naproxen enantiomers on weak chiral anion-exchangers in nonlinear chromatography

    SciTech Connect

    Asnin, Leonid; Kaczmarski, Krzysztof; Guiochon, Georges A

    The retention mechanism of the enantiomers of naproxen on a Pirkle-type chiral stationary phase (CSP) was studied. This CSP is made of a porous silica grafted with quinidine carbamate. It can interact with the weak organic electrolyte naproxen either by adsorbing it or by ion-exchange. Using frontal chromatography, we explored the adsorption equilibrium under such experimental conditions that naproxen dissociates or cannot dissociate. Under conditions preventing ionic dissociation, the adsorption isotherms were measured, the adsorption energy distributions determined, and the chromatographic profiles calculated. Three different types of the adsorption sites were found for both enantiomers. The density and the bindingmore » energy of these sites depend on the nature of the organic modifier. Different solute species, anions, neutral molecules, solvent-ion associates, and solute dimers can coexist in solution, giving rise to different forms of adsorption. This study showed the unexpected occurrence of secondary steps in the breakthrough profiles of S-naproxen in the adsorption mode at high concentrations. Being enantioselective, this phenomenon was assumed to result from the association of solute molecules involving a chiral selector moiety. A multisite Langmuir adsorption model was used to calculate band profiles. Although this model accounts excellently for the experimental adsorption isotherms, it does not explain all the features of the breakthrough profiles. A comparison between the calculated and experimental profiles allowed useful conclusions concerning the effects of the adsorbate-adsorbate and adsorbate-solvent interactions on the adsorption mechanism.« less

  19. Distinct enantiomeric signals of ibuprofen and naproxen in treated wastewater and sewer overflow.

    PubMed

    Khan, Stuart J; Wang, Lili; Hashim, Nor H; McDonald, James A

    2014-11-01

    Ibuprofen and naproxen are commonly used members of a class of pharmaceuticals known as 2-arylpropionic acids (2-APAs). Both are chiral chemicals and can exist as either of two (R)- and (S)-enantiomers. Enantioselective analyses of effluents from municipal wastewater treatment plants (WWTPs) and from untreated sewage overflow reveal distinctly different enantiomeric fractions for both pharmaceuticals. The (S)-enantiomers of both were dominant in untreated sewage overflow, but the relative proportions of the (R)-enantiomers were shown to be increased in WWTP effluents. (R)-naproxen was below method detection limits (<1 ng.L(-1)) in sewage overflow, but measurable at higher concentrations in WWTP effluents. Accordingly, enantiomeric fractions (EF) for naproxen were consistently 1.0 in sewage overflow, but ranged from 0.7–0.9 in WWTP effluents. Ibuprofen EF ranged from 0.6–0.8 in sewage overflow and receiving waters, and was 0.5 in two WWTP effluents. Strong evidence is provided to indicate that chiral inversion of (S)-2-APAs to produce (R)-2-APAs may occur during wastewater treatment processes. It is concluded that this characterization of the enantiomeric fractions for ibuprofen and naproxen in particular effluents could facilitate the distinction of treated and untreated sources of pharmaceutical contamination in surface waters.

  20. Effect of anthocyanins on expression of matrix metalloproteinase-2 in naproxen-induced gastric ulcers.

    PubMed

    Kim, Sun-Joong; Park, Young Sam; Paik, Hyun-Dong; Chang, Hyo Ihl

    2011-12-01

    Non-steroidal anti-inflammatory drugs cause gastric ulceration through a number of mechanisms including inhibition of PG synthesis, generation of reactive oxygen species (ROS) and induction of apoptosis. Recently, matrix metalloproteinases (MMP) have been suggested to play a crucial role in these mechanisms. The present study investigated the protective effect of anthocyanins isolated from black rice bran (Heugjinjubyeo) against naproxen-induced gastric mucosal injury in rats. The oral administration of anthocyanins (5, 25 or 50 mg/kg body weight) showed significant protection against naproxen (80 mg/kg body weight)-induced gastric ulcer and inhibited lipid peroxidation in the gastric mucosa. In addition, pretreatment with anthocyanins resulted in a significant increase in the activities of radical-scavenging enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Also biochemical and zymographic analyses suggested that the administration of anthocyanins gives a significant protection against naproxen-induced gastric antral ulcer through scavenging ROS and regulation of matrix metalloproteinase-2 (MMP-2) activity. The results of intracellular radical activation show that anthocyanins suppress the generation of intracellular ROS and attenuate the suppression of MMP-2 activity by naproxen. These results suggest that anthocyanins extracted from black rice may offer potential remedy of gastric antral ulceration.

  1. Sonocatalytic removal of naproxen by synthesized zinc oxide nanoparticles on montmorillonite.

    PubMed

    Karaca, Melike; Kıranşan, Murat; Karaca, Semra; Khataee, Alireza; Karimi, Atefeh

    2016-07-01

    ZnO/MMT nanocomposite as sonocatalyst was prepared by immobilizing synthesized ZnO on the montmorillonite surface. The characteristics of as-prepared nanocomposite were studied by scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM) and X-ray diffraction (XRD) techniques. The synthesized samples were used as a catalyst for sonocatalytic degradation of naproxen. ZnO/MMT catalyst in the presence of ultrasound irradiation was more effective compared to pure ZnO nanoparticles and MMT particles in the sonocatalysis of naproxen. The effect of different operational parameters on the sonocatalytic degradation of naproxen including initial drug concentration, sonocatalyst dosage, solution pH, ultrasonic power and the presence of organic and inorganic scavengers were evaluated. It was found that the presence of the scavengers suppressed the sonocatalytic degradation efficiency. The reusability of the nanocomposite was examined in several consecutive runs, and the degradation efficiency decreased only 2% after 5 repeated runs. The main intermediates of naproxen degradation were determined by gas chromatography-mass spectrometry (GC-Mass). Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Roles of functional groups of naproxen in its sorption to kaolinite.

    PubMed

    Yu, Chenglong; Bi, Erping

    2015-11-01

    The sorption of acidic anti-inflammatory drugs to soils is important for evaluating their fate and transformations in the water-soil environment. However, roles of functional groups of ionisable drugs onto mineral surfaces have not been sufficiently studied. In this study, batch experiments of naproxen (NPX, anti-inflammatory drug) and two kinds of competitors to kaolinite were studied. The Kd of naproxen to kaolinite is 1.30-1.62 L kg(-1). The n-π electron donor-acceptor (n-π EDA) interaction between diaromatic ring of naproxen (π-electron acceptors) and the siloxane oxygens (n-donors) of kaolinite is the dominant sorption mechanism. The carboxyl group of naproxen can contribute to the overall sorption. A conception model was put forward to elucidate to sorption mechanisms, in which the contribution of n-π EDA and hydrogen bond to overall sorption was quantified. These sorption mechanisms can be helpful for estimating the fate and mobility of acid pharmaceuticals in soil-water environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Naproxen Attenuates Sensitization of Depressive-Like Behavior and Fever during Maternal Separation

    PubMed Central

    Hennessy, Michael B.; Stafford, Nathan P.; Yusko-Osborne, Brittany; Schiml, Patricia A.; Xanthos, Evan D.; Deak, Terrence

    2014-01-01

    Early life stress can increase susceptibility for later development of depressive illness though a process thought to involve inflammatory mediators. Isolated guinea pig pups exhibit a passive, depressive-like behavioral response and fever that appear mediated by proinflammatory activity, and which sensitize with repeated separations. Treatment with an anti-inflammatory can attenuate the behavioral response during the initial separation and separation the following day. Here we used the cyclooxygenase inhibitor naproxen to examine the role of prostaglandins in mediating the depressive-like behavior and core body temperature of young guinea pigs during an initial separation, separation the next day, and separation 10 days after the first. The passive, depressive-like behavior as well as fever sensitized with repeated separation. Three days of injection with 14 mg/kg of naproxen prior to the initial separation reduced depressive-like behavior during all three separations. A 28 mg/kg dose of naproxen, however, had minimal effect on behavior. Fever during the early separations was moderated by naproxen, but only at the higher dose. These results suggest a role of prostaglandins in the behavioral and febrile response to maternal separation, and particularly in the sensitization of depressive-like behavior following repeated separation. PMID:25449392

  4. Liposomal Aloe vera trans-emulgel drug delivery of naproxen and nimesulide: A study

    PubMed Central

    Venkataharsha, Panuganti; Maheshwara, Ellutla; Raju, Y Prasanna; Reddy, Vayalpati Ashok; Rayadu, Bandugalla Sanjeev; Karisetty, Basappa

    2015-01-01

    Introduction: The present aim of this study was to formulate naproxen and nimesulide liposomal formulation for incorporation in Aloe vera transemulgel and to carry out in vitro and in vivo evaluation of the formulation. Material and Methods: A. vera gel was prepared and used as a gel base for formulation. Carbopol 934 is used as a gelling agent and Methyl paraben was used as a preservative for the formulation of the gel. Liposomes was formulated by using hydration method. The formulated naproxen and nimesulide liposomal formulation using A. vera trans-emul gel were evaluated for in vitro studies such as drug release, permeation study, and drug content and entrapment efficiency. Paw edema method in Wistar rats induced by carrageenan is used to study in vivo anti-inflammatory action. Result: From the in vitro studies such permeability drug release naproxen 65% (69.6), Nimesulide 65% (61.1), and commercial Nimsulide gel (60.82) at 240 min. In vivo data shows that formulated liposomal transemulgel formulation are superior in their efficacy compared to commercial and A. vera gel. The results are compared with the commercial formulations. Conclusion: From our results, it is concluded that the A. vera trans emul gel using nimesulide and naproxen liposomal formulation is stable and prepared gel base is effective for formulation with high drug release and drug content compared with commercial formulation with significant anti-inflammatory effect. PMID:25599030

  5. Enthalpies of Dissolution of Crystalline Naproxen Sodium in Water and Potassium Hydroxide Aqueous Solutions at 298 K

    NASA Astrophysics Data System (ADS)

    Lytkin, A. I.; Chernikov, V. V.; Krutova, O. N.; Bychkova, S. A.; Volkov, A. V.; Skvortsov, I. A.

    2018-03-01

    The enthalpies of dissolution of crystalline naproxen sodium in water and aqueous solutions of KOH at 298.15 K are measured by direct calorimetric means in a wide range of concentrations. The acid-base properties of naproxen sodium at ionic strength I 0 and I = 0.1 (KNO3) and a temperature of 298.15 K are studied by spectrophotometric means. The concentration and thermodynamic dissociation constants are determined. The standard enthalpies of the formation of naproxen sodium and the products of its dissociation in aqueous solution are calculated.

  6. Analysis of acute naproxen administration on memory in young adults: A randomized, double-blind, placebo-controlled study.

    PubMed

    Wilson, Jack H; Criss, Amy H; Spangler, Sean A; Walukevich, Katherine; Hewett, Sandra

    2017-10-01

    Nonsteroidal anti-inflammatory drugs work by non-selectively inhibiting cyclooxygenase enzymes. Evidence indicates that metabolites of the cyclooxygenase pathway play a critical role in the process of learning and memory. We evaluated whether acute naproxen treatment impairs short-term working memory, episodic memory, or semantic memory in a young, healthy adult population. Participants received a single dose of placebo or naproxen (750 mg) in random order separated by 7-10 days. Two hours following administration, participants completed five memory tasks. The administration of acute high-dose naproxen had no effect on memory in healthy young adults.

  7. Suppository naproxen reduces incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis: Randomized controlled trial.

    PubMed

    Mansour-Ghanaei, Fariborz; Joukar, Farahnaz; Taherzadeh, Zahra; Sokhanvar, Homayoon; Hasandokht, Tolou

    2016-06-07

    To determine the efficacy of rectally administered naproxen for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). This double-blind randomized control trial conducted from January 2013 to April 2014 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 324 patients were selected from candidates for diagnostic or therapeutic ERCP by using the simple sampling method. Patients received a single dose of Naproxen (500 mg; n = 162) or a placebo (n = 162) per rectum immediately before ERCP. The overall incidence of PEP, incidence of mild to severe PEP, serum amylase levels and adverse effects were measured. The primary outcome measure was the development of pancreatitis onset of pain in the upper abdomen and elevation of the serum amylase level to > 3 × the upper normal limit (60-100 IU/L) within 24 h after ERCP. The severity of PEP was classified according to the duration of therapeutic intervention for PEP: mild, 2-3 d; moderate 4-10 d; and severe, > 10 d and/or necessitated surgical or intensive treatment, or contributed to death. PEP occurred in 12% (40/324) of participants, and was significantly more frequent in the placebo group compared to the naproxen group (P < 0.01). Of the participants, 25.9% (84/324) developed hyperamylasemia within 2 h of procedure completion, among whom only 35 cases belonged to the naproxen group (P < 0.01). The incidence of PEP was significantly higher in female sex, in patients receiving pancreatic duct injection, more than 3 times pancreatic duct cannulations, and ERCP duration more than 40 min (Ps < 0.01). There were no statistically significant differences between the groups regarding the procedures or factors that might increase the risk of PEP, sphincterotomy, precut requirement, biliary duct injection and number of pancreatic duct cannulations. In the subgroup of patients with pancreatic duct injection, the rate of pancreatitis in the naproxen group was

  8. Removal of carbamazepine and naproxen by immobilized Phanerochaete chrysosporium under non-sterile condition.

    PubMed

    Li, Xueqing; de Toledo, Renata Alves; Wang, Shengpeng; Shim, Hojae

    2015-03-25

    This study explored the utilization of a white-rot fungus (WRF), Phanerochaete chrysosporium, immobilized in wood chips, to remove carbamazepine and naproxen under non-sterile condition. The removal efficiencies for both pharmaceutically active compounds (PhACs) in artificially contaminated water were improved by 4% for naproxen and 30% for carbamazepine in seven days, compared to without wood chips. Although adsorption was crucial at the early stage, bioremoval was found to be the main removal mechanism for both PhACs. The extracellular enzymes played important roles in the naproxen removal, while the intracellular enzyme system was responsible for the carbamazepine removal. The increased of intracellular enzyme activity through the immobilization of WRF cells may contribute to the significantly enhanced removal efficiency for carbamazepine. In addition, the removal of naproxen or carbamazepine slightly increased when both compounds coexisted, compared to the system where the two pharmaceuticals existed separately. Based on the batch experimental results, a fixed-bed bioreactor packed with a mixture of WRF mycelia pellets and wood chips was developed and operated with the intermittent feeding and continuous aerating mode for 28 days under non-sterile condition, with naproxen and carbamazepine spiked into the influent at 1.0 mg L(-1). Almost complete removal of naproxen and 60-80% removal of carbamazepine were obtained in the first two weeks. However, the removal efficiencies for both compounds suddenly dropped to as low as less than 20% by the 14th day, possibly due to the contamination by other microorganisms in the reactor. After the addition of 8.25% sodium hypochlorite at the ratio of 1:100 (v/v) into the influent tank on both Day 20 and Day 25, a rapid recovery (higher than 95%) was achieved in the naproxen removal, by effectively inhibiting contamination in the reactor. In comparison, the same rebounding phenomenon was not observed for carbamazepine and this

  9. Development of a solid self-microemulsifying drug delivery system (SMEDDS) for solubility enhancement of naproxen.

    PubMed

    Čerpnjak, Katja; Zvonar, Alenka; Vrečer, Franc; Gašperlin, Mirjana

    2015-01-01

    Comparative evaluation of liquid and solid self-microemulsifying drug delivery systems (SMEDDS) as promising approaches for solubility enhancement. The aim of this work was to develop, characterize, and evaluate a solid SMEDDS prepared via spray-drying of a liquid SMEDDS based on Gelucire® 44/14 to improve the solubility and dissolution rate of naproxen. Various oils and co-surfactants in combination with Gelucire® 44/14 were evaluated during excipient selection study, solubility testing, and construction of (pseudo)ternary diagrams. The selected system was further evaluated for naproxen solubility, self-microemulsification ability, and in vitro dissolution of naproxen. In addition, its transformation into a solid SMEDDS by spray-drying using maltodextrin as a solid carrier was performed. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to evaluate the physical characteristics of the solid SMEDDS obtained. The selected formulation of SMEDDS was comprised of Miglyol 812®, Peceol™, Gelucire® 44/14, and Solutol® HS 15. The liquid and solid SMEDDS formed a microemulsion after dilution with comparable average droplet size and exhibited uniform droplet size distribution. In the solid SMEDDS, liquid SMEDDS was adsorbed onto the surface of maltodextrin and formed smooth granular particles with the encapsulated drug predominantly in a dissolved state and partially in an amorphous state. Overall, incorporation of naproxen in SMEDDS, either liquid or solid, resulted in improved solubility and dissolution rate compared to pure naproxen. This study indicates that a liquid and solid SMEDDS is a strategy for solubility enhancement in the future development of orally delivered dosage forms.

  10. Studying of crystal growth and overall crystallization of naproxen from binary mixtures.

    PubMed

    Kaminska, E; Madejczyk, O; Tarnacka, M; Jurkiewicz, K; Kaminski, K; Paluch, M

    2017-04-01

    Broadband dielectric spectroscopy (BDS) and differential scanning calorimetry (DSC) were applied to investigate the molecular dynamics and phase transitions in binary mixtures composed of naproxen (NAP) and acetylated saccharides: maltose (acMAL) and sucrose (acSUC). Moreover, the application of BDS method and optical microscopy enabled us to study both crystallization kinetics and crystal growth of naproxen from the solid dispersions with the highest content of modified carbohydrates (1:5wt ratio). It was found that the activation barriers of crystallization estimated from dielectric measurements are completely different for both studied herein mixtures. Much higher E a (=205kJ/mol) was obtained for NAP-acMAL solid dispersion. It is probably due to simultaneous crystallization of both components of the mixture. On the other hand, lower value of E a in the case of NAP-acSUC solid dispersion (81kJ/mol) indicated, that naproxen is the only crystallizing compound. This hypothesis was confirmed by X-ray diffraction studies. We also suggested that specific intermolecular dipole-dipole interactions between active substance and excipient may be an alternative explanation for the difference between activation barrier obtained for NAP-acMAL and NAP-acSUC binary mixtures. Furthermore, optical measurements showed that the activation energy for crystal growth of naproxen increases in binary mixtures. They also revealed that both excipients: acMAL and acSUC move the temperature of the maximum of crystal growth towards lower temperatures. Interestingly, this maximum occurs for nearly the same structural relaxation time, which is a good approximation of viscosity, for all samples. Finally, it was also noticed that although naproxen crystallizes to the same polymorphic form in both systems, there are some differences in morphology of obtained crystals. Thus, the observed behavior may have a significant impact on the bioavailability and dissolution rate of API produced in that way

  11. Naproxen Sodium for Pain Control With Intrauterine Device Insertion: A Randomized Controlled Trial.

    PubMed

    Ngo, Lynn L; Braaten, Kari P; Eichen, Eva; Fortin, Jennifer; Maurer, Rie; Goldberg, Alisa B

    2016-12-01

    To evaluate whether 550 mg oral naproxen sodium given 1 hour before intrauterine device (IUD) insertion is effective for pain relief as compared with placebo. This was a randomized, double-blind, placebo-controlled trial. The primary outcome was pain with IUD insertion measured on a 100-mm visual analog scale (VAS). Our sample size was calculated to detect a 15-mm difference in VAS scores with 80% power (α=0.05). Secondary outcomes included pain with tenaculum placement, uterine sounding, and 5 and 15 minutes postinsertion. A total of 118 women were enrolled and analyzed (58 in the naproxen sodium arm, 60 in the placebo arm, 97% nulliparous) between May 11, 2015, and March 25, 2016. There were no differences in baseline demographics or reproductive characteristics between arms. There were no differences in median VAS pain scores for the primary outcome of pain with IUD insertion between the naproxen sodium arm compared with the placebo arm (69 compared with 66 mm, P=.89). There were no differences in the secondary outcomes of median VAS pain scores with tenaculum placement (37 compared with 32 mm, P=.97) or uterine sounding (60 compared with 58 mm, P=.66). However, median pain scores postprocedure were lower in the naproxen arm as compared with the placebo arm: 17 compared with 26 mm (P=.01) at 5 minutes and 13 compared with 24 mm (P=.01) at 15 minutes postinsertion. Oral naproxen sodium does not reduce pain with IUD insertion but does reduce pain after insertion and should be considered as a premedication. ClinicalTrials.gov, http://clinicaltrials.gov, NCT02388191.

  12. Structure-Based Discovery of the Novel Antiviral Properties of Naproxen against the Nucleoprotein of Influenza A Virus

    PubMed Central

    Lejal, Nathalie; Tarus, Bogdan; Bouguyon, Edwige; Chenavas, Sylvie; Bertho, Nicolas; Delmas, Bernard; Ruigrok, Rob W. H.; Di Primo, Carmelo

    2013-01-01

    The nucleoprotein (NP) binds the viral RNA genome and associates with the polymerase in a ribonucleoprotein complex (RNP) required for transcription and replication of influenza A virus. NP has no cellular counterpart, and the NP sequence is highly conserved, which led to considering NP a hot target in the search for antivirals. We report here that monomeric nucleoprotein can be inhibited by a small molecule binding in its RNA binding groove, resulting in a novel antiviral against influenza A virus. We identified naproxen, an anti-inflammatory drug that targeted the nucleoprotein to inhibit NP-RNA association required for NP function, by virtual screening. Further docking and molecular dynamics (MD) simulations identified in the RNA groove two NP-naproxen complexes of similar levels of interaction energy. The predicted naproxen binding sites were tested using the Y148A, R152A, R355A, and R361A proteins carrying single-point mutations. Surface plasmon resonance, fluorescence, and other in vitro experiments supported the notion that naproxen binds at a site identified by MD simulations and showed that naproxen competed with RNA binding to wild-type (WT) NP and protected active monomers of the nucleoprotein against proteolytic cleavage. Naproxen protected Madin-Darby canine kidney (MDCK) cells against viral challenges with the H1N1 and H3N2 viral strains and was much more effective than other cyclooxygenase inhibitors in decreasing viral titers of MDCK cells. In a mouse model of intranasal infection, naproxen treatment decreased the viral titers in mice lungs. In conclusion, naproxen is a promising lead compound for novel antivirals against influenza A virus that targets the nucleoprotein in its RNA binding groove. PMID:23459490

  13. Comparison of the analgesic effects of oral tramadol and naproxen sodium on pain relief during IUD insertion.

    PubMed

    Karabayirli, Safinaz; Ayrim, Aylin Aker; Muslu, Bunyamin

    2012-01-01

    To compare the analgesic efficacy of oral tramadol and naproxen sodium on pain during insertion of an intrauterine device (IUD). Randomized, double-blinded, clinical trial (Canadian Task Force classification I). University-affiliated hospital. Single-center. One hundred three patients scheduled for insertion of an IUD. Patients were randomly assigned to receive oral tramadol 50 mg capsules (n = 35) or naproxen sodium 550 mg tablets (n = 34) or placebo (n = 34) 1 hour before insertion of the IUD. After insertion of the IUD, pain intensity was evaluated using a visual analog scale (VAS, 0-10). Adverse effects, patient satisfaction with the medication, and preference for using it during future insertions were also recorded. The VAS scores were significantly different during IUD insertion among the 3 groups (p = .001). Pain scores in the tramadol group were significantly lower than in the naproxen group (p = .003), and the scores in the naproxen group was significantly lower than in the control group (p = .001). Patient satisfaction with the medication and preference for its future use were significantly lower in the control group than in the other 2 groups (p = .001). Prophylactic analgesia using 50 mg tramadol and 550 mg naproxen, delivered orally, can be used to relieve pain during IUD insertion. However, tramadol capsules were found to be more effective than naproxen tablets. Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.

  14. Chiral recognition of naproxen enantiomers based on fluorescence quenching of bovine serum albumin-stabilized gold nanoclusters

    NASA Astrophysics Data System (ADS)

    Jafari, Marzieh; Tashkhourian, Javad; Absalan, Ghodratollah

    2017-10-01

    A simple, fast and green method for chiral recognition of S- and R-naproxen has been introduced. The method was based on quenching of the fluorescence intensity of bovine serum albumin-stabilized gold nanoclusters in the presence of naproxen enantiomers. The quenching intensity in the presence of S-naproxen was higher than R-naproxen when phosphate buffer solution at pH 7.0 was used. The chiral recognition occurred due to steric effect between bovine serum albumin conformation and naproxen enantiomers. Two linear determination range were established as 7.4 × 10-7-9.1 × 10-6 and 9.1 × 10-6-3.1 × 10-5 mol L-1 for both enantiomers and detection limits of 7.4 × 10-8 mol L- 1 and 9.5 × 10-8 mol L-1 were obtained for S- and R-naproxen, respectively. The developed method showed good repeatability and reproducibility for the analysis of a synthetic sample. To make the procedure applicable to biological samples, the removal of heavy metals from the sample is suggested before any analytical attempt.

  15. Removal of acetaminophen and naproxen by combined coagulation and adsorption using biochar: influence of combined sewer overflow components.

    PubMed

    Jung, Chanil; Oh, Jeill; Yoon, Yeomin

    2015-07-01

    The combined coagulation and adsorption of targeted acetaminophen and naproxen using activated biochar and aluminum sulfate were studied under various synthetic "combined sewer overflow" (CSO) conditions. The biochar demonstrated better adsorption performance for both acetaminophen and naproxen (removal, 94.1 and 97.7%, respectively) than that of commercially available powdered activated carbon (removal, 81.6 and 94.1%, respectively) due to superior carbonaceous structure and surface properties examined by nuclear magnetic resonance analysis. The adsorption of naproxen was more favorable, occupying active adsorption sites on the adsorbents by naproxen due to its higher adsorption affinity compared to acetaminophen. Three classified CSO components (i.e., representing hydrophobic organics, hydrophilic organics, and inorganics) played different roles in the adsorption of both adsorbates, resulted in inhibition by humic acid complexation or metal ligands and negative electrostatic repulsion under adsorption and coagulation combined system. Adsorption alone with biochar was determined to be the most effective adsorptive condition for the removal of both acetaminophen and naproxen under various CSO conditions, while both coagulation alone and combined adsorption and coagulation failed to remove the acetaminophen and naproxen adequately due to an increase in ionic strength in the presence of spiked aluminum species derived from the coagulant.

  16. Naproxen induces cell cycle arrest and apoptosis in human urinary bladder cancer cell lines and chemically induced cancers by targeting PI3-K

    PubMed Central

    Kim, Mi-Sung; Kim, Jong-Eun; Lim, Do Young; Huang, Zunnan; Chen, Hanyong; Langfald, Alyssa; Lubet, Ronald A.; Grubbs, Clinton J.; Dong, Zigang; Bode, Ann M.

    2014-01-01

    Naproxen ((S)-6-methoxy-α-methyl-2-naphthaleneacetic acid) is a potent nonsteroidal anti-inflammatory drug that inhibits both COX-1 and COX-2 and is widely used as an over-the-counter medication. Naproxen exhibits analgesic, anti-pyretic, and anti-inflammatory activities. Naproxen, as well as other NSAIDS, has been reported to be effective in the prevention of urinary bladder cancer in rodents. However, potential targets other than the COX isozymes have not been reported. We examined potential additional targets in urinary bladder cancer cells and in rat bladder cancers. Computer kinase profiling results suggested that phosphatidylinositol 3-kinase (PI3-K) is a potential target for naproxen. In vitro kinase assay data revealed that naproxen interacts with PI3-K and inhibits its kinase activity. Pull-down binding assay data confirmed that PI3-K directly binds with naproxen in vitro and ex vivo. Western blot data showed that naproxen decreased phosphorylation of Akt, and subsequently decreased Akt signaling in UM-UC-5 and UMUC-14 urinary bladder cancer cells. Furthermore, naproxen suppressed anchorage-independent cell growth and decreased cell viability by targeting PI3-K in both cell lines. Naproxen caused an accumulation of cells at the G1 phase mediated through CDK4, cyclin D1 and p21. Moreover, naproxen induced significant apoptosis, accompanied with increased levels of cleaved caspase 3, caspase 7, and poly (ADP-ribose) polymerase (PARP) in both cell types. Naproxen-induced cell death was mainly due to apoptosis in which a prominent down-regulation of Bcl-2 and up-regulation of Bax were involved. Naproxen also caused apoptosis and inhibited Akt phosphorylation in rat urinary bladder cancers induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN). PMID:24327721

  17. Occurrence and fate of carbamazepine, clofibric acid, diclofenac, ibuprofen, ketoprofen, and naproxen in surface waters.

    PubMed

    Tixier, Céline; Singer, Heinz P; Oellers, Sjef; Müller, Stephan R

    2003-03-15

    Although various single-concentration measurements of pharmaceuticals are available in the literature, detailed information on the variation over time of the concentration and the load in wastewater effluents and rivers and on the fate of these compounds in the aquatic environment are lacking. We measured the concentrations of six pharmaceuticals, carbamazepine, clofibric acid, diclofenac, ibuprofen, ketoprofen, and naproxen, in the effluents of three wastewater treatment plants (WWTPs), in two rivers and in the water column of Lake Greifensee (Switzerland) over a time period of three months. In WWTP effluents, the concentrations reached 0.95 microg/L for carbamazepine, 0.06 microg/L for clofibric acid, 0.99 microg/L for diclofenac, 1.3 microg/L for ibuprofen, 0.18 microg/L for ketoprofen, and 2.6 microg/L for naproxen. The relative importance in terms of loads was carbamazepine, followed by diclofenac, naproxen, ibuprofen, clofibric acid, and ketoprofen. An overall removal rate of all these pharmaceuticals was estimated in surface waters, under real-world conditions (in a lake), using field measurements and modeling. Carbamazepine and clofibric acid were fairly persistent. Phototransformation was identified as the main elimination process of diclofenac in the lake water during the study period. With a relatively high sorption coefficient to particles, ibuprofen might be eliminated by sedimentation. For ketoprofen and naproxen, biodegradation and phototransformation might be elimination processes. For the first time, quantitative data regarding removal rates were determined in surface waters under real-world conditions. All these findings are important data for a risk assessment of these compounds in surface waters.

  18. [Severe toxic liver failure after acute poisoning with paracetamol, ferrous sulphate and naproxen].

    PubMed

    Adamek, Robert; Wilczek, Lech; Krupiński, Bogusław

    2004-01-01

    We present the case of 20-year-old woman intoxicated with mixed drugs, composed of paracetamol (acetaminophen), ferrous sulphate, naproxen and benzodiazepines. Acute toxic liver damage with clinical symptoms of coma resolved at the patient. Lack of the past history doesn't let to specific therapy and systemic complications. In this data we confirm, that past history, clinical symptoms and laboratory results are needed in designing a treatment strategy.

  19. Use of DMPC and DSPC lipids for verapamil and naproxen permeability studies by PAMPA.

    PubMed

    Alvarez-Figueroa, M J; Contreras-Garrido, B C; Soto-Arriaza, M A

    2015-04-01

    Verapamil and naproxen Parallel Artificial Membrane Permeability Assay (PAMPA) permeability was studied using lipids not yet reported for this model in order to facilitate the quantification of drug permeability. These lipids are 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and an equimolar mixture of DMPC/DSPC, both in the absence and in the presence of 33.3 mol% of cholesterol. PAMPA drug permeability using the lipids mentioned above was compared with lecithin-PC. The results show that verapamil permeability depends on the kind of lipid used, in the order DMPC > DMPC/DSPC > DSPC. The permeability of the drugs was between 1.3 and 3.5-times larger than those obtained in lecithin-PC for all the concentrations of the drug used. Naproxen shows similar permeability than verapamil; however, the permeability increased with respect to lecithin-PC only when DMPC and DMPC/DSPC were used. This behavior could be explained by a difference between the drug net charge at pH 7.4. On the other hand, in the presence of cholesterol, verapamil permeability increases in all lipid systems; however, the relative verapamil permeability respect to lecithin-PC did not show any significant increase. This result is likely due to the promoting effect of cholesterol, which is not able to compensate for the large increase in verapamil permeability observed in lecithin-PC. With respect to naproxen, its permeability value and relative permeability respect lecithin-PC not always increased in the presence of cholesterol. This result is probably attributed to the negative charge of naproxen rather than its molecular weight. The lipid systems studied have an advantage in drug permeability quantification, which is mainly related to the charge of the molecule and not to its molecular weight or to cholesterol used as an absorption promoter.

  20. Naproxen Microparticulate Systems Prepared Using In Situ Crystallisation and Freeze-Drying Techniques.

    PubMed

    Solaiman, Amanda; Tatari, Adam Keenan; Elkordy, Amal Ali

    2017-07-01

    Poor drug solubility and dissolution rate remain to be one of the major problems facing pharmaceutical scientists, with approximately 40% of drugs in the industry categorised as practically insoluble or poorly water soluble. This in turn can lead to serious delivery challenges and poor bioavailability. The aim of this research was to investigate the effects of the surfactants, poloxamer 407 (P407) and caprol® PGE 860 (CAP), at various concentrations (0.1, 0.5, 1 and 3% w/v) on the enhancement of the dissolution properties of poorly water-soluble drug, naproxen, using in situ micronisation by solvent change method and freeze-drying. The extent at which freeze-drying influences the dissolution rate of naproxen microcrystals is investigated in this study by comparison with desiccant-drying. All formulations were evaluated and characterised using particle size analysis and morphology, in vitro dissolution studies, differential scanning calorimetry (DSC), and Fourier transform infra-red (FT-IR) spectroscopy. An increase in poloxamer 407 concentration in freeze-dried formulations led to enhancement of drug dissolution compared to desiccator-dried formulations, naproxen/caprol® PGE 860 formulations and untreated drug. DSC and FT-IR results show no significant chemical interactions between drug and poloxamer 407, with only very small changes to drug crystallinity. On the other hand, caprol® PGE 860 showed some interactions with drug components, alterations to the crystal lattice of naproxen, and poor dissolution profiles using both drying methods, making it a poor choice of excipient.

  1. Comparison of the efficacy and safety of nonprescription doses of naproxen and naproxen sodium with ibuprofen, acetaminophen, and placebo in the treatment of primary dysmenorrhea: a pooled analysis of five studies.

    PubMed

    Milsom, Ian; Minic, Milos; Dawood, M Yusoff; Akin, Mark D; Spann, June; Niland, Nona F; Squire, R Anne

    2002-09-01

    Dysmenorrhea is the most common menstrual complaint in young women, with a prevalence as high as 90%. It is responsible for substantial repeated short-term absenteeism from school and work in young women. Effective treatments are available, including nonsteroidal anti-inflammatory drugs (NSAIDs). In many countries, a variety of NSAIDs have become available as over-the-counter (OTC) drugs. The goal of this study was to compare the efficacy and safety of OTC doses of naproxen (400 mg) and naproxen/naproxen sodium (200/220 mg) with acetaminophen (1000 mg), ibuprofen (200 mg), and placebo in the treatment of primary dysmenorrhea. A pooled analysis of 5 trials was performed. Efficacy was assessed by pain relief, relief of other dysmenorrheic symptoms, time to backup medication or remedication, and treatment preference. Tolerability was assessed by recording adverse events (AEs). A total of 443 women were enrolled in the combined studies. Naproxen 400 mg provided greater pain relief than acetaminophen and placebo within 30 minutes of administration (P < 0.01 and P < 0.05, respectively). Furthermore, naproxen 400 mg and 200 mg provided greater pain relief than both acetaminophen (P < 0.01 and P < 0.05, respectively) and ibuprofen (P < 0.001 and P < 0.01, respectively) at 6 hours after administration. Both doses of naproxen had higher scores than placebo for symptom relief and drug preference (all P < 0.001). The AEs and their frequency were similar among the treatment groups. No serious AEs were reported. When administered at OTC doses, naproxen was effective in the relief of pain and other symptoms of primary dysmenorrhea and had a good safety profile in the population studied.

  2. Encapsulation of Naproxen in Lipid-Based Matrix Microspheres: Characterization and Release Kinetics

    PubMed Central

    Bhoyar, PK; Morani, DO; Biyani, DM; Umekar, MJ; Mahure, JG; Amgaonkar, YM

    2011-01-01

    The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix. PMID:21731354

  3. Encapsulation of naproxen in lipid-based matrix microspheres: characterization and release kinetics.

    PubMed

    Bhoyar, P K; Morani, D O; Biyani, D M; Umekar, M J; Mahure, J G; Amgaonkar, Y M

    2011-04-01

    The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix.

  4. Enantioselective synthesis of (S)-naproxen using immobilized lipase on chitosan beads.

    PubMed

    Gilani, Saeedeh L; Najafpour, Ghasem D; Heydarzadeh, Hamid D; Moghadamnia, Aliakbar

    2017-06-01

    S-naproxen by enantioselective hydrolysis of racemic naproxen methyl ester was produced using immobilized lipase. The lipase enzyme was immobilized on chitosan beads, activated chitosan beads by glutaraldehyde, and Amberlite XAD7. In order to find an appropriate support for the hydrolysis reaction of racemic naproxen methyl ester, the conversion and enantioselectivity for all carriers were compared. In addition, effects of the volumetric ratio of two phases in different organic solvents, addition of cosolvent and surfactant, optimum pH and temperature, reusability, and inhibitory effect of methanol were investigated. The optimum volumetric ratio of two phases was defined as 3:2 of aqueous phase to organic phase. Various water miscible and water immiscible solvents were examined. Finally, isooctane was chosen as an organic solvent, while 2-ethoxyethanol was added as a cosolvent in the organic phase of the reaction mixture. The optimum reaction conditions were determined to be 35 °C, pH 7, and 24 h. Addition of Tween-80 in the organic phase increased the accessibility of immobilized enzyme to the reactant. The optimum organic phase compositions using a volumetric ratio of 2-ethoxyethanol, isooctane and Tween-80 were 3:7 and 0.1% (v/v/v), respectively. The best conversion and enantioselectivity of immobilized enzyme using chitosan beads activated by glutaraldehyde were 0.45 and 185, respectively. © 2017 Wiley Periodicals, Inc.

  5. Chiral recognition ability of an (S)-naproxen- imprinted monolith by capillary electrochromatography.

    PubMed

    Xu, Yan-Li; Liu, Zhao-Sheng; Wang, He-Fang; Yan, Chao; Gao, Ru-Yu

    2005-02-01

    The racemic naproxen was selectively recognized by capillary electrochromatography (CEC) on an (S)-naproxen-imprinted monolith, which was prepared by an in situ thermal-initiated polymerization. The recognition selectivity of a selected monolith strictly relied on the CEC conditions involved. The factors that influence the imprinting selectivity as well as the electroosmotic flow (EOF), including the applied voltage, organic solvent, salt concentration and pH value of the buffer, column temperature, and surfactant modifiers were systematically studied. Once the column was prepared, the experiment results showed that the successful chiral recognition was dependent on CEC variables. For example: the recognition could be observed in acetonitrile and ethanol electrolytes, while methanol and dimethyl sulfoxide (DMSO) electrolytes had no chiral recognition ability. The buffer with pH values of 2.6 or 3.0 at a higher salt concentration had chiral recognition ability. Column temperatures of 25-35 degrees C were optimal. Three surfactants, sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and polyoxyethylene sorbitan monolaurate (Tween 20), can improve the recognition. Baseline resolution was obtained under optimized conditions and the column efficiency of the later eluent (S)-naproxen was 90 000 plates/m.

  6. Preparation and recrystallization behavior of spray-dried co-amorphous naproxen-indomethacin.

    PubMed

    Beyer, Andreas; Radi, Lydia; Grohganz, Holger; Löbmann, Korbinian; Rades, Thomas; Leopold, Claudia S

    2016-07-01

    To improve the dissolution properties and the physical stability of amorphous active pharmaceutical ingredients, small molecule stabilizing agents may be added to prepare co-amorphous systems. The objective of the study was to investigate if spray-drying allows the preparation of co-amorphous drug-drug systems such as naproxen-indomethacin and to examine the influence of the process conditions on the resulting initial sample crystallinity and the recrystallization behavior of the drug(s). For this purpose, the process parameters inlet temperature and pump feed rate were varied according to a 2(2) factorial design and the obtained samples were analyzed with X-ray powder diffractometry and Fourier-transformed infrared spectroscopy. Evaluation of the data revealed that the preparation of fully amorphous samples could be achieved depending on the process conditions. The resulting recrystallization behavior of the samples, such as the total recrystallization rate, the individual recrystallization rates of naproxen and indomethacin as well as the polymorphic form of indomethacin that was formed were influenced by these process conditions. For initially amorphous samples, it was found that naproxen and indomethacin recrystallized almost simultaneously, which supports the theory of formation of drug-drug heterodimers in the co-amorphous phase. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Investigating flavour characteristics of British ale yeasts: techniques, resources and opportunities for innovation

    PubMed Central

    Parker, Neva; James, Steve; Dicks, Jo; Bond, Chris; Nueno-Palop, Carmen; White, Chris; Roberts, Ian N

    2015-01-01

    Five British ale yeast strains were subjected to flavour profiling under brewery fermentation conditions in which all other brewing parameters were kept constant. Significant variation was observed in the timing and quantity of flavour-related chemicals produced. Genetic tests showed no evidence of hybrid origins in any of the strains, including one strain previously reported as a possible hybrid of Saccharomyces cerevisiae and S. bayanus. Variation maintained in historical S. cerevisiae ale yeast collections is highlighted as a potential source of novelty in innovative strain improvement for bioflavour production. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25361168

  8. Posteriori error determination and grid adaptation for AMR and ALE computational fluid dynamics

    SciTech Connect

    Lapenta, G. M.

    2002-01-01

    We discuss grid adaptation for application to AMR and ALE codes. Two new contributions are presented. First, a new method to locate the regions where the truncation error is being created due to an insufficient accuracy: the operator recovery error origin (OREO) detector. The OREO detector is automatic, reliable, easy to implement and extremely inexpensive. Second, a new grid motion technique is presented for application to ALE codes. The method is based on the Brackbill-Saltzman approach but it is directly linked to the OREO detector and moves the grid automatically to minimize the error.

  9. Effect of Naproxen Prophylaxis on Heterotopic Ossification Following Hip Arthroscopy: A Double-Blind Randomized Placebo-Controlled Trial.

    PubMed

    Beckmann, James T; Wylie, James D; Potter, Michael Q; Maak, Travis G; Greene, Thomas H; Aoki, Stephen K

    2015-12-16

    Heterotopic ossification (HO) is a known complication of hip arthroscopy. Our objective was to determine the effect of postoperative naproxen therapy on the development of HO following arthroscopic surgery for femoroacetabular impingement. Between August 2011 and April 2013, 108 eligible patients were enrolled and randomized to take naproxen or a placebo for three weeks postoperatively. Radiographs were made at routine follow-up visits for one year following surgery. The primary outcome measure was the development of HO, as classified with the Brooker criteria and two-dimensional measurements on radiographs made at least seventy-five days postoperatively (average, 322 days). The primary analysis, performed with a Fisher exact test, compared the proportion of subjects with HO between the treatment and control groups. A single a priori interim analysis was planned at the midpoint of the study. Our data safety and monitoring board stopped this study when the interim analysis showed that the stopping criterion had been met for demonstration of efficacy of the naproxen intervention. The prevalence of HO was 46% (twenty-two of the forty-eight in the final analysis) in the placebo group versus 4% (two of forty-eight) in the naproxen group (p < 0.001). Medication compliance was 69% overall, but it did not differ between the naproxen and placebo groups. Minor adverse reactions to the study medications were reported in 42% of the patients taking naproxen versus 35% of those taking the placebo (p = 0.45). In this trial, prophylaxis with naproxen was effective in reducing the prevalence of HO without medication-related morbidity. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

  10. Efficacy and safety of intravenous tanezumab for the symptomatic treatment of osteoarthritis: 2 randomized controlled trials versus naproxen.

    PubMed

    Ekman, Evan F; Gimbel, Joseph S; Bello, Alfonso E; Smith, Michael D; Keller, David S; Annis, Karen M; Brown, Mark T; West, Christine R; Verburg, Kenneth M

    2014-11-01

    Two studies evaluated efficacy and safety of tanezumab versus naproxen for treatment of knee or hip osteoarthritis (OA). Randomized controlled studies [NCT00830063 (Study 1015, n=828) and NCT00863304 (Study 1018, n=840)] of subjects with hip or knee OA compared intravenous tanezumab (5 mg or 10 mg) to placebo and naproxen (500 mg twice daily). Coprimary outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function (0-10 numerical rating scale), and patient's global assessment of OA at Week 16. In both studies, tanezumab reduced pain versus placebo [least squares mean differences, 95% CI, tanezumab 5 mg: -1.21 (-1.72, -0.70); -1.13 (-1.65, -0.62); tanezumab 10 mg: -0.91 (-1.42, -0.40); -0.80 (-1.32, -0.29)], and improved function and global scores. Tanezumab 5 mg produced greater pain reduction [-0.76 (-1.28, -0.25); -0.69 (-1.21, -0.17)], and favorable functional and global outcomes versus naproxen. Pain reductions with tanezumab 10 mg versus naproxen did not reach significance, unlike functional (both studies) and global (1 study) outcomes; thus, tanezumab 10 mg was not superior to naproxen, and predefined statistical testing procedures were not met, allowing for conclusion of superiority of tanezumab 5 mg over naproxen despite replicated favorable coprimary outcomes. Tanezumab was associated with greater incidence of peripheral sensory adverse events (paresthesia, hyperesthesia, hypoesthesia, burning sensation), pain in extremity, peripheral edema, and arthralgia. Overall frequency and discontinuations as a result of adverse events were similar to placebo and naproxen. Tanezumab provides efficacious treatment of knee or hip OA and may have therapeutic utility in patients with OA who experience inadequate analgesia with nonsteroidal antiinflammatory drugs.

  11. Mucosal healing effect of mesalazine granules in naproxen-induced small bowel enteropathy

    PubMed Central

    Rácz, István; Szalai, Milán; Kovács, Valéria; Regőczi, Henriett; Kiss, Gyöngyi; Horváth, Zoltán

    2013-01-01

    AIM: To investigate the effect of mesalazine granules on small intestinal injury induced by naproxen using capsule endoscopy (CE). METHODS: This was a single center, non-randomized, open-label, uncontrolled pilot study, using the PillCam SB CE system with RAPID 5 software. The Lewis Index Score (LIS) for small bowel injury was investigated to evaluate the severity of mucosal injury. Arthropathy patients with at least one month history of daily naproxen use of 1000 mg and proton pump inhibitor co-therapy were screened. Patients with a minimum LIS of 135 were eligible to enter the 4-wk treatment phase of the study. During this treatment period, 3 × 1000 mg/d mesalazine granules were added to ongoing therapies of 1000 mg/d naproxen and 20 mg/d omeprazole. At the end of the 4-wk combined treatment period, a second small bowel CE was performed to re-evaluate the enteropathy according to the LIS results. The primary objective of this study was to assess the mucosal changes after 4 wk of mesalazine treatment. RESULTS: A total of 18 patients (16 females), ranging in age from 46 to 78 years (mean age 60.3 years) were screened, all had been taking 1000 mg/d naproxen for at least one month. Eight patients were excluded from the mesalazine therapeutic phase of the study for the following reasons: the screening CE showed normal small bowel mucosa or only insignificant damages (LIS < 135) in five patients, the screening esophagogastroduodenoscopy revealed gastric ulcer in one patient, capsule technical failure and incomplete CE due to poor small bowel cleanliness in two patients. Ten patients (9 female, mean age 56.2 years) whose initial LIS reached mild and moderate-to-severe enteropathy grades (between 135 and 790 and ≥ 790) entered the 4-wk therapeutic phase and a repeat CE was performed. When comparing the change in LIS from baseline to end of treatment in all patients, a marked decrease was seen (mean LIS: 1236.4 ± 821.9 vs 925.2 ± 543.4, P = 0.271). Moreover, a

  12. Naproxcinod shows significant advantages over naproxen in the mdx model of Duchenne Muscular Dystrophy.

    PubMed

    Miglietta, Daniela; De Palma, Clara; Sciorati, Clara; Vergani, Barbara; Pisa, Viviana; Villa, Antonello; Ongini, Ennio; Clementi, Emilio

    2015-08-22

    In dystrophin-deficient muscles of Duchenne Muscular Dystrophy (DMD) patients and the mdx mouse model, nitric oxide (NO) signalling is impaired. Previous studies have shown that NO-donating drugs are beneficial in dystrophic mouse models. Recently, a long-term treatment (9 months) of mdx mice with naproxcinod, an NO-donating naproxen, has shown a significant improvement of the dystrophic phenotype with beneficial effects present throughout the disease progression. It remains however to be clearly dissected out which specific effects are due to the NO component compared with the anti-inflammatory activity associated with naproxen. Understanding the contribution of NO vs the anti-inflammatory effect is important, in view of the potential therapeutic perspective, and this is the final aim of this study. Five-week-old mdx mice received either naproxcinod (30 mg/kg) or the equimolar dose of naproxen (20 mg/kg) in the diet for 6 months. Control mdx mice were used as reference. Treatments (or vehicle for control groups) were administered daily in the diet. For the first 3 months the study was performed in sedentary animals, then all mice were subjected to exercise until the sixth month. Skeletal muscle force was assessed by measuring whole body tension in sedentary animals as well as in exercised mice and resistance to fatigue was measured after 3 months of running exercise. At the end of 6 months of treatment, animals were sacrificed for histological analysis and measurement of naproxen levels in blood and skeletal muscle. Naproxcinod significantly ameliorated skeletal muscle force and resistance to fatigue in sedentary as well as in exercised mice, reduced inflammatory infiltrates and fibrosis deposition in both cardiac and diaphragm muscles. Conversely, the equimolar dose of naproxen showed no effects on fibrosis and improved muscle function only in sedentary mice, while the beneficial effects in exercised mice were lost demonstrating a limited and short

  13. Sumatriptan plus naproxen for the treatment of acute migraine attacks in adults.

    PubMed

    Law, Simon; Derry, Sheena; Moore, R Andrew

    2016-04-20

    This is an updated version of the original Cochrane review published in October 2013 on 'Sumatriptan plus naproxen for acute migraine attacks in adults'.Migraine is a common disabling condition and a burden for the individual, health services, and society. It affects two to three times more women than men, and is most common in the age range 30 to 50 years. Effective abortive treatments include the triptan and non-steroidal anti-inflammatory classes of drugs. These drugs have different mechanisms of action and combining them may provide better relief. Sumatriptan plus naproxen is now available in combination form for the acute treatment of migraine. To determine the efficacy and tolerability of sumatriptan plus naproxen, administered together as separate tablets or taken as a fixed-dose combination tablet, compared with placebo and other active interventions in the treatment of acute migraine attacks in adults. For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) via The Cochrane Register of Studies Online (CRSO) to 28 October 2015, MEDLINE (via Ovid) from 1946 to 28 October 2015, and EMBASE (via Ovid) from 1974 to 28 October 2015, and two online databases (www.gsk-clinicalstudyregister.com and www.clinicaltrials.gov). We also searched the reference lists of included studies and relevant reviews. We included randomised, double-blind, placebo- or active-controlled studies, with at least 10 participants per treatment arm, using sumatriptan plus naproxen to treat a migraine headache episode. Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate risk ratio and numbers needed to treat for an additional beneficial outcome (NNT) or for an additional harmful outcome (NNH) compared with placebo or a different active treatment. For this update we identified one new study (43 participants), but it did not contribute any data for analysis. The review

  14. Diazepam Is No Better Than Placebo When Added to Naproxen for Acute Low Back Pain.

    PubMed

    Friedman, Benjamin W; Irizarry, Eddie; Solorzano, Clemencia; Khankel, Nauman; Zapata, Jennifer; Zias, Eleftheria; Gallagher, E John

    2017-08-01

    Low back pain causes more than 2.5 million visits to US emergency departments (EDs) annually. Low back pain patients are often treated with nonsteroidal anti-inflammatory drugs and benzodiazepines. The former is an evidence-based intervention, whereas the efficacy of the latter has not been established. We compare pain and functional outcomes 1 week and 3 months after ED discharge among patients randomized to a 1-week course of naproxen+diazepam versus naproxen+placebo. This was a randomized, double-blind, comparative efficacy clinical trial conducted in an urban health care system. Patients presenting with acute, nontraumatic, nonradicular low back pain of no more than a duration of 2 weeks were eligible for enrollment immediately before discharge from an ED if they had a score greater than 5 on the Roland-Morris Disability Questionnaire, a validated 24-item inventory of functional impairment caused by low back pain. Higher scores on the questionnaire indicate greater functional disability. The primary outcome in the trial was improvement in the score between ED discharge and 1 week later. Secondary outcomes included pain intensity 1 week and 3 months after ED discharge, as measured on a 4-point descriptive scale (severe, moderate, mild, and none). All patients were given 20 tablets of naproxen 500 mg, to be taken twice a day as needed for low back pain. Additionally, patients were randomized to receive either 28 tablets of diazepam 5 mg or identical placebo, to be received as 1 or 2 tablets every 12 hours as needed for low back pain. All patients received a standardized 10-minute low back pain educational session before discharge. Using a between-group mean difference of 5 Roland-Morris Disability Questionnaire points, a previously validated threshold for clinical significance, we calculated the need for at least 100 patients with primary outcome data. Enrollment began in June 2015 and continued for 9 months. Five hundred forty-five patients were screened for

  15. Improving the drug release of Naproxen Sodium tablets by preparing granules and tablets with a preferred mixing ratio of hydrates.

    PubMed

    Bär, David; Debus, Heiko; Grune, Christian; Tosch, Stephan; Fischer, Wolfgang; Mäder, Karsten; Imming, Peter

    2017-12-01

    Naproxen is a typical and well-known analgesic classified as non-steroidal anti-inflammatory drug (NSAID) and is commercialized as tablets or liquid-filled capsules. Naproxen is typically used asa sodium salt because of its better processability compared to Naproxen free acid. This entails hygroscopicity and gives rise to the existence of four different hydrates, which show polymorphic and pseudopolymorphic properties. Solid dosage forms containing Naproxen Sodium often have to be processed in an applicable dosage form by granulation and tablet compression. During granulation, Naproxen Sodium will be in contact with water and is exposed to the drop and rise in temperature and to mechanical stress. The result could be a mixture of different hydrates of Naproxen Sodium. This study showed that a modified designed fluid bed granulation was not affected by differences in the mixing ratio of hydrates when using different water contents after spraying and at the end with the finished granules. Here, X-ray diffraction combined with Rietveld refinement was used to analyze the ratio of the hydrates and its identity. All granulation batches showed a large amount of Naproxen Sodium Monohydrate (>87%) and no differences could be observed during tablet compression. Quantities of other hydrates were negligibly small. Furthermore, this study also demonstrated the influence of tablet compression by transforming the hydrates of the granules. In addition to Naproxen Sodium Monohydrate, a large quantity of amorphous structures has also been found. Rietveld evaluation combined with the preliminary studies of the raw hydrates provided conclusions on the drug release of the tablets containing hydrates of Naproxen Sodium which were influenced by tablet compression. Fast drug release was obtained when a maximum water content of about 21% was used after spraying during granulation, independently of the final water content of the finished granules. A maximum water content of less than 21

  16. Pharmacokinetic profile of extended-release versus immediate-release oral naproxen sodium after single and multiple dosing under fed and fasting conditions: two randomized, open-label trials.

    PubMed

    Laurora, Irene; Wang, Yuan

    2016-10-01

    Extended-release (ER) naproxen sodium provides pain relief for up to 24 hours with a single dose (660 mg/day). Its pharmacokinetic profile after single and multiple dosing was compared to immediate release (IR) naproxen sodium in two randomized, open-label, crossover studies, under fasting and fed conditions. Eligible healthy subjects were randomized to ER naproxen sodium 660-mg tablet once daily or IR naproxen sodium 220-mg tablet twice daily (440 mg initially, followed by 220 mg 12 hours later). Primary variables: pharmacokinetic parameters after singleday administration (day 1) and at steady state after multiple-day administration (day 6). Total exposure was comparable for both treatments under fasting and fed conditions. After fasting: peak naproxen concentrations were slightly lower with ER naproxen sodium than with IR naproxen sodium but were reached at a similar time. Fed conditions: mean peak concentrations were comparable but reached after a longer time with ER vs. IR naproxen sodium. ER naproxen sodium was well tolerated, with a similar safety profile to IR naproxen sodium. The total exposure of ER naproxen sodium (660 mg) is comparable to IR naproxen sodium (220 mg) when administered at the maximum over the counter (OTC) dose of 660-mg daily dose on a single day and over multiple days. The rate of absorption is delayed under fed conditions.

  17. Curcumin Blocks Naproxen-Induced Gastric Antral Ulcerations through Inhibition of Lipid Peroxidation and Activation of Enzymatic Scavengers in Rats.

    PubMed

    Kim, Jeong-Hwan; Jin, Soojung; Kwon, Hyun Ju; Kim, Byung Woo

    2016-08-28

    Curcumin is a polyphenol derived from the plant Curcuma longa, which is used for the treatment of diseases associated with oxidative stress and inflammation. The present study was undertaken to determine the protective effect of curcumin against naproxen-induced gastric antral ulcerations in rats. Different doses (10, 50, and 100 mg/kg) of curcumin or vehicle (curcumin, 0 mg/kg) were pretreated for 3 days by oral gavage, and then gastric mucosal lesions were caused by 80 mg/kg naproxen applied for 3 days. Curcumin significantly inhibited the naproxen-induced gastric antral ulcer area and lipid peroxidation in a dose-dependent manner. In addition, curcumin markedly increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Specifically, 100 mg/kg curcumin completely protected the gastric mucosa against the loss in the enzyme, resulting in a drastic increase of activities of radical scavenging enzymes up to more than the level of untreated normal rats. Histological examination obviously showed that curcumin prevents naproxen-induced gastric antral ulceration as a result of direct protection of the gastric mucosa. These results suggest that curcumin blocks naproxen-induced gastric antral ulcerations through prevention of lipid peroxidation and activation of radical scavenging enzymes, and it may offer a potential remedy of gastric antral ulcerations.

  18. Modelling of pain intensity and informative dropout in a dental pain model after naproxcinod, naproxen and placebo administration

    PubMed Central

    Björnsson, Marcus A; Simonsson, Ulrika S H

    2011-01-01

    AIMS To describe pain intensity (PI) measured on a visual analogue scale (VAS) and dropout due to request for rescue medication after administration of naproxcinod, naproxen or placebo in 242 patients after wisdom tooth removal. METHODS Non-linear mixed effects modelling was used to describe the plasma concentrations of naproxen, either formed from naproxcinod or from naproxen itself, and their relationship to PI and dropout. Goodness of fit was assessed by simultaneous simulations of PI and dropout. RESULTS Baseline PI for the typical patient was 52.7 mm. The PI was influenced by placebo effects, using an exponential model, and by naproxen concentrations using a sigmoid Emax model. Typical maximal placebo effect was a decrease in PI by 20.2%, with an onset rate constant of 0.237 h−1. EC50 was 0.135 µmol l−1. A Weibull time-to-event model was used for the dropout, where the hazard was dependent on the predicted PI and by the PI at baseline. Since the dropout was not at random, it was necessary to include the simulated dropout in visual predictive checks (VPC) of PI. CONCLUSIONS This model describes the relationship between drug effects, PI and the likelihood of dropout after naproxcinod, naproxen and placebo administration. The model provides an opportunity to describe the effects of other doses or formulations, after dental extraction. VPC created by simultaneous simulations of PI and dropout provides a good way of assessing the goodness of fit when there is informative dropout. PMID:21272053

  19. Arylhydrazone derivatives of naproxen as new analgesic and anti-inflammatory agents: Design, synthesis and molecular docking studies.

    PubMed

    Azizian, Homa; Mousavi, Zahra; Faraji, Hamidreza; Tajik, Mohammad; Bagherzadeh, Kowsar; Bayat, Peyman; Shafiee, Abbas; Almasirad, Ali

    2016-06-01

    A series of new arylidenehydrazone derivatives of naproxen were synthesized and evaluated for their analgesic and anti-inflammatory activities. Some of the synthesized analogues showed comparable activities when compared against naproxen for their analgesic and anti-inflammatory properties. 2-(6-methoxy-2-naphthyl)-N'-[(pyridine-4-yl)methylene]propanoic acid hydrazide 4j was found to be the most active analgesic agent. 2-(6-methoxy-2-naphthyl)-N'-[4-nitrobenzylidene]propanoic acid hydrazide 4g showed highest anti-inflammatory activity in comparison to the naproxen. Molecular modeling study of the synthesized compounds suggested that the designed molecules were well located and bound to the COX-1 and COX-2 active sites. Compound 4g showed the highest selectivity for COX-2 (RCOX-2/COX-1=1.94) and higher affinity rather than naproxen in COX-2 active site (RCOX-2/naproxen=1.28). Moreover, the structural analyses confirmed that the E-ap rotamer is the preferred structure for the arylidenehydrazone derivatives. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine

    PubMed Central

    Lal, Ritu; Sukbuntherng, Juthamas; Luo, Wendy; Vicente, Virna; Blumenthal, Robin; Ho, Judy; Cundy, Kenneth C

    2010-01-01

    AIM Gabapentin enacarbil, a transported prodrug of gabapentin, provides sustained, dose-proportional exposure to gabapentin. Unlike gabapentin, the prodrug is absorbed throughout the intestinal tract by high-capacity nutrient transporters, including mono-carboxylate transporter-1 (MCT-1). Once absorbed, gabapentin enacarbil is rapidly hydrolyzed to gabapentin, which is subsequently excreted by renal elimination via organic cation transporters (OCT2). To examine the potential for drug–drug interactions at these two transporters, the pharmacokinetics of gabapentin enacarbil were evaluated in healthy adults after administration alone or in combination with either naproxen (an MCT-1 substrate) or cimetidine (an OCT2 substrate). METHODS Subjects (n= 12 in each study) received doses of study drug until steady state was achieved; 1200 mg gabapentin enacarbil each day, followed by either naproxen (500 mg twice daily) or cimetidine (400 mg four times daily) followed by the combination. RESULTS When gabapentin enacarbil was co-administered with naproxen, gabapentin Css,max increased by, on average, 8% and AUC by, on average, 13%. When gabapentin enacarbil was co-administered with cimetidine, gabapentin AUCss increased by 24% and renal clearance of gabapentin decreased. Co-administration with gabapentin enacarbil did not affect naproxen or cimetidine exposure. Gabapentin enacarbil was generally well tolerated. CONCLUSIONS No gabapentin enacarbil dose adjustment is needed with co-administration of naproxen or cimetidine. PMID:20573085

  1. Naproxen sodium decreases prostaglandins secretion from cultured human endometrial stromal cells modulating metabolizing enzymes mRNA expression.

    PubMed

    Carrarelli, Patrizia; Funghi, Lucia; Bruni, Simone; Luisi, Stefano; Arcuri, Felice; Petraglia, Felice

    2016-01-01

    Dysmenorrhea, defined as painful cramps occurring immediately before or during the menstrual period, is a common symptom of different gynecological diseases. An acute uterine inflammatory response driven by prostaglandins (PGs) is responsible for painful symptoms. Progesterone withdrawal is responsible for activation of cyclooxygenase (COX-2) enzyme and decrease of hydroxyprostaglandin dehydrogenase (HPDG) with consequent increased secretion of PGs secretion, inducing uterine contractility and pain. The most widely used drugs for the treatment of pelvic pain associated with menstrual cycle are non steroidal anti-inflammatory drugs (NSAIDs). The uterine site of action of these drugs is still not defined and the present study evaluated the effect of naproxen sodium in cultured human endometrial stromal cells (HESC) collected from healthy women. PGE2 release was measured by ELISA; COX-2 and HPDG mRNA expression were assessed by qRT-PCR. Naproxen sodium did not affect HESC vitality. Naproxen sodium significantly decreased PGE2 secretion (p < 0.01) and COX-2 mRNA expression (p < 0.01). TNF-α induced PGE2 release was reduced in presence of naproxen sodium (p < 0.05), in association with decreased COX-2 and increased HPDG mRNAs expression. Naproxen sodium decreases endometrial PGE2 release induced by inflammatory stimulus acting on endometrial COX-2 and HPDG expression, suggesting endometrial synthesis of prostaglandins as a possible target for reduction of uterine inflammatory mechanism in dysmenorrhea.

  2. 47 CFR 87.149 - Special requirements for automatic link establishment (ALE).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Special requirements for automatic link establishment (ALE). 87.149 Section 87.149 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AVIATION SERVICES Technical Requirements § 87.149 Special requirements...

  3. Protective Effect of 4-(3,4-Dihydroxyphenyl)-3-Buten-2-One from Phellinus linteus on Naproxen-Induced Gastric Antral Ulcers in Rats.

    PubMed

    Kim, Jeong-Hwan; Kwon, Hyun Ju; Kim, Byung Woo

    2016-05-28

    The present study investigated the protective effect of naturally purified 4-(3,4- dihydroxyphenyl)-3-buten-2-one (DHP) from Phellinus linteus against naproxen-induced gastric antral ulcers in rats. To verify the protective effect of DHP on naproxen-induced gastric antral ulcers, various doses (1, 5, and 10 μg/kg) of DHP were pretreated for 3 days, and then gastric damage was caused by 80 mg/kg naproxen applied for 3 days. DHP prevented naproxen-induced gastric antral ulcers in a dose-dependent manner. In particular, 10 μg/kg DHP showed the best protective effect against naproxen-induced gastric antral ulcers. Moreover, DHP significantly attenuated the naproxen-induced lipid peroxide level in gastric mucosa and increased the activities of radical scavenging enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, in a dose-dependent manner. A histological examination clearly demonstrated that the gastric antral ulcer induced by naproxen nearly disappeared after the pretreatment of DHP. These results suggest that DHP can inhibit naproxen-induced gastric antral ulcers through prevention of lipid peroxidation and activation of radical scavenging enzymes.

  4. Modeling Three-Dimensional Shock Initiation of PBX 9501 in ALE3D

    SciTech Connect

    Leininger, L; Springer, H K; Mace, J

    A recent SMIS (Specific Munitions Impact Scenario) experimental series performed at Los Alamos National Laboratory has provided 3-dimensional shock initiation behavior of the HMX-based heterogeneous high explosive, PBX 9501. A series of finite element impact calculations have been performed in the ALE3D [1] hydrodynamic code and compared to the SMIS results to validate and study code predictions. These SMIS tests used a powder gun to shoot scaled NATO standard fragments into a cylinder of PBX 9501, which has a PMMA case and a steel impact cover. This SMIS real-world shot scenario creates a unique test-bed because (1) SMIS tests facilitatemore » the investigation of 3D Shock to Detonation Transition (SDT) within the context of a considerable suite of diagnostics, and (2) many of the fragments arrive at the impact plate off-center and at an angle of impact. A particular goal of these model validation experiments is to demonstrate the predictive capability of the ALE3D implementation of the Tarver-Lee Ignition and Growth reactive flow model [2] within a fully 3-dimensional regime of SDT. The 3-dimensional Arbitrary Lagrange Eulerian (ALE) hydrodynamic model in ALE3D applies the Ignition and Growth (I&G) reactive flow model with PBX 9501 parameters derived from historical 1-dimensional experimental data. The model includes the off-center and angle of impact variations seen in the experiments. Qualitatively, the ALE3D I&G calculations reproduce observed 'Go/No-Go' 3D Shock to Detonation Transition (SDT) reaction in the explosive, as well as the case expansion recorded by a high-speed optical camera. Quantitatively, the calculations show good agreement with the shock time of arrival at internal and external diagnostic pins. This exercise demonstrates the utility of the Ignition and Growth model applied for the response of heterogeneous high explosives in the SDT regime.« less

  5. Efficacy of single-dose, extended-release naproxen sodium 660 mg in postsurgical dental pain: two double-blind, randomized, placebo-controlled trials.

    PubMed

    Laurora, Irene; An, Robert

    2016-01-01

    To evaluate the efficacy of a novel formulation of extended-release/immediate-release (ER) naproxen sodium over 24 h in a dental pain model. Two randomized, double-blind, placebo-controlled trials in moderate to severe pain after extraction of one or two impacted third molars (at least one partial mandibular bony impaction). Treatment comprised oral ER naproxen sodium 660 mg (single dose), placebo (both studies) or immediate-release (IR) naproxen sodium 220 mg tid (study 2). Primary efficacy endpoint: 24-h summed pain intensity difference (SPID). Secondary variables included total pain relief (TOTPAR), use of rescue medication. All treatment-emergent adverse events were recorded. NCT00720057 (study 1), NCT01389284 (study 2). Primary efficacy analyses: pain intensity was significantly lower over 24 h with ER naproxen sodium vs. placebo (p < 0.001), with significant relief from 15 min (study 2). In study 2, ER naproxen sodium was non-inferior to IR naproxen sodium, reducing pain intensity to a comparable extent over 24 h. TOTPAR was significantly greater with ER and IR naproxen sodium vs. placebo at all time points, with generally comparable differences between active treatments. Significantly more placebo patients required rescue medication vs. ER and IR naproxen sodium from 2-24 h post-dose. Once daily ER naproxen sodium was generally safe and well tolerated, with a similar safety profile to IR naproxen sodium tid. The studies were single dose, with limited ability to assess efficacy or safety of multiple doses over time. As the imputed pain score meant that estimated treatment differences may have been biased in favor of ER naproxen sodium, a post hoc analysis evaluated the robustness of the results for pain relief. A single dose of ER naproxen sodium 660 mg significantly reduced moderate to severe dental pain vs. placebo and was comparable to IR naproxen sodium 220 mg tid. Significant pain relief was experienced from 15 min and sustained

  6. Microenvironmental pH measurement during sodium naproxenate dissolution in acidic medium by UV/vis imaging.

    PubMed

    Østergaard, Jesper; Jensen, Henrik; Larsen, Susan W; Larsen, Claus; Lenke, Jim

    2014-11-01

    Variable dissolution from sodium salts of drugs containing a carboxylic acid group after passing the acidic environment of the stomach may affect oral bioavailability. The aim of the present proof of concept study was to investigate pH effects in relation to the dissolution of sodium naproxenate in 0.01M hydrochloric acid. For this purpose a UV/vis imaging-based approach capable of measuring microenvironmental pH in the vicinity of the solid drug compact as well as monitoring drug dissolution was developed. Using a pH indicating dye real-time spatially resolved measurement of pH was achieved. Sodium naproxenate, can significantly alter the local pH of the dissolution medium, is eventually neutralized and precipitates as the acidic species naproxen. The developed approach is considered useful for detailed studies of pH dependent dissolution phenomena in dissolution testing. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial.

    PubMed

    Yeomans, N D; Graham, D Y; Husni, M E; Solomon, D H; Stevens, T; Vargo, J; Wang, Q; Wisniewski, L M; Wolski, K E; Borer, J S; Libby, P; Lincoff, A M; Lüscher, T F; Bao, W; Walker, C; Nissen, S E

    2018-06-01

    To evaluate GI safety of celecoxib compared with 2 nonselective (ns) NSAIDs, as a secondary objective of a large trial examining multiorgan safety. This randomised, double-blind controlled trial analysed 24 081 patients. Osteoarthritis or rheumatoid arthritis patients, needing ongoing NSAID treatment, were randomised to receive celecoxib 100-200 mg b.d., ibuprofen 600-800 mg t.d.s. or naproxen 375-500 mg b.d. plus esomeprazole, and low-dose aspirin or corticosteroids if already prescribed. Clinically significant GI events (CSGIE-bleeding, obstruction, perforation events from stomach downwards or symptomatic ulcers) and iron deficiency anaemia (IDA) were adjudicated blindly. Mean treatment and follow-up durations were 20.3 and 34.1 months. While on treatment or 30 days after, CSGIE occurred in 0.34%, 0.74% and 0.66% taking celecoxib, ibuprofen and naproxen. Hazard ratios (HR) were 0.43 (95% CI 0.27-0.68, P = 0.0003) celecoxib vs ibuprofen and 0.51 (0.32-0.81, P = 0.004) vs naproxen. There was also less IDA on celecoxib: HR 0.43 (0.27-0.68, P = 0.0003) vs ibuprofen; 0.40 (0.25-0.62, P < 0.0001) vs naproxen. Even taken with low-dose aspirin, fewer CSGIE occurred on celecoxib than ibuprofen (HR 0.52 [0.29-0.94], P = 0.03), and less IDA vs naproxen (0.42 [0.23-0.77, P = 0.005]). Corticosteroid use increased total GI events and CSGIE. H. pylori serological status had no influence. Arthritis patients taking NSAIDs plus esomeprazole have infrequent clinically significant gastrointestinal events. Co-prescribed with esomeprazole, celecoxib has better overall GI safety than ibuprofen or naproxen at these doses, despite treatment with low-dose aspirin or corticosteroids. © 2018 John Wiley & Sons Ltd.

  8. Characterization of the anti-inflammatory properties of NCX 429, a dual-acting compound releasing nitric oxide and naproxen.

    PubMed

    Amoruso, Angela; Fresu, Luigia Grazia; Dalli, Jesmond; Miglietta, Daniela; Bardelli, Claudio; Federici Canova, Donata; Perretti, Mauro; Brunelleschi, Sandra

    2015-04-01

    Cyclooxygenase (COX)-inhibiting nitric oxide donors (CINODs) are a new class of drugs that structurally combine a COX inhibitor with a nitric oxide (NO) donating moiety. This combination reduces potential toxicity of the non-steroidal anti-inflammatory drugs (NSAIDs) whilst maintaining the analgesic and anti-inflammatory effects. The present study was undertaken to investigate the anti-inflammatory effects of NCX 429, a naproxen-based CINOD, and to assess the additional properties of NO donation beyond those related to naproxen. We evaluated the in vitro effects of NCX 429 on oxy-radical production, phagocytosis, cytokine release, MMP-9, PPARγ expression and NF-κB activation in human monocytes/MDM and compared to naproxen. Moreover, we compared the in vivo efficacy of NCX 429 and naproxen in a murine model of peritonitis. In all the experiments performed in vitro, NCX 429 reduced the inflammatory responses with equal or higher efficacy compared to naproxen. Moreover, in in vivo experiments, NCX 429, at the lowest dose tested, was able to significantly inhibit cell influx in response to IL-1β administration although naproxen was found to be more potent than NCX 429 at reducing PGE2 in inflammatory exudates. These results demonstrate that both in vitro and in vivo--in a murine model of peritonitis--NCX 429 elicits significant anti-inflammatory activity, beyond the simple COX inhibition or pure NO release. Therefore, NO donation along with COX inhibition may represent a strategy for investigating inflammatory diseases in which pain and function are not fully resolved by analgesics/anti-inflammatory drugs. © 2015.

  9. An examination of the thermodynamics of fusion, vaporization, and sublimation of ibuprofen and naproxen by correlation gas chromatography.

    PubMed

    Maxwell, Rachel; Chickos, James

    2012-02-01

    The vaporization enthalpies of (S)-ibuprofen and (S)-naproxen measured by correlation gas chromatography at T = 298.15 K are reported and compared with literature values. Adjustment of the fusion enthalpies of (RS)- and (S)-ibuprofen and (S)-naproxen to T = 298.15 K and combined with the vaporization enthalpy of the (S)-enantiomer of both ibuprofen and naproxen also at T = 298.15 K resulted in the sublimation enthalpies of both (S)-enantiomers. On the assumption that the vaporization enthalpy of the racemic form of ibuprofen is within the experimental uncertainty of the chiral form, the sublimation enthalpy of racemic ibuprofen was also evaluated. The vaporization and sublimation enthalpies compare favorably to the most of the literature values for the racemic form of ibuprofen but differ from the value reported for chiral ibuprofen. The literature values of (S)-naproxen are somewhat smaller than the values measured in this work. The following vaporization enthalpies were measured for (S)-ibuprofen and (S)-naproxen, respectively: ΔH(vap) (298.15 K), 106.0 ± 5.5, 132.2 ± 5.0 kJ·mol(-1) . Sublimation enthalpies of 122.7 ± 5.6 and 155.2 ± 7.1 kJ·mol(-1) were calculated for the (S)-enantiomers of ibuprofen and naproxen and a value of 128.9 ± 5.8 kJ·mol(-1) was estimated for the racemic form of ibuprofen. Copyright © 2011 Wiley Periodicals, Inc.

  10. Cost analysis of flavocoxid compared to naproxen for management of mild to moderate OA.

    PubMed

    Walton, Surrey M; Schumock, Glen T; McLain, David Andrew

    2010-09-01

    Flavocoxid is a medical food used for the clinical dietary management of osteoarthritis (OA). The acquisition cost of flavocoxid is higher than most traditional, generic NSAIDs. However, flavocoxid may have more favorable gastrointestinal (GI) toxicity resulting in lower overall costs. These costs have not been previously examined. This study provides a decision analytic model to assess the net costs of using flavocoxid for OA from a Medicare perspective. A decision model was developed to estimate the total costs associated with flavocoxid versus naproxen for the management of Medicare patients with mild to moderate OA. Probabilities were obtained from literature and expert opinion, and costs were obtained from Medicare. Sensitivity analyses were conducted by varying probabilities and costs within clinically relevant ranges. The base case resulted in flavocoxid having lower total annual costs ($1482 per patient) compared to naproxen ($1592). Flavocoxid remained the lowest cost option when the cost inputs were varied by 25% (above and below the base case), and when the probability of GI events with flavocoxid were varied by 25%. However, when GI rates from the literature and implied relative risks from the expert panel were used, or if the cost of PPIs was $0, then naproxen was the less costly alternative, though saving less than the annual cost of flavocoxid. Key limitations were the limited outcomes in the model (only GI events), lack of consideration of adherence or combination therapy, and the reliance on expert opinion due to a lack of data for flavocoxid. In patients over 65 years of age who suffer from mild to moderate OA, flavocoxid may result in lower overall costs, despite a higher acquisition cost. Managed care organizations should consider total health care costs in the decision to include flavocoxid as a covered benefit.

  11. Role of humic substances in the photodegradation of naproxen under simulated sunlight.

    PubMed

    Chen, Yong; Liu, Lu; Su, Jing; Liang, Jianfeng; Wu, Bo; Zuo, Jiaolan; Zuo, Yuegang

    2017-11-01

    Humic substances (HS) including humic acid (HA) and fulvic acid (FA) are ubiquitous in the natural waters. Although numerous studies documented their role in photodegradation of organic pollutants, the competitive effects of photosensitization and light-screening of HS on the photodegradation of pollutants are not yet clear. In this work, the role of HS in the photodegradation of the pharmaceutical naproxen (NP) was studied under simulated sunlight. The direct photodegradation quantum yield of NP in deionized water was 2.1 × 10 -2 , and the apparent quantum yields for photosensitized degradation of NP in the presence of FA and HA were 2.3 × 10 -4 and 2.6 × 10 -5 , respectively. Both direct and photosensitized photodegradation decreased with increasing pH, consistent with the trend of singlet oxygen ( 1 O 2 ) reaction rate constants of NP. HA inhibited the photodegradation of naproxen thoroughly. In contrast, FA accelerated the photodegradation of NP at lower substrate concentration and light intensity, and vice versa. Direct photodegradation of NP declined sharply with spectral radiation attenuation of UV region, when HS-mediated photosensitization predominantly accounted for the photodegradation. The direct photodegradation was ascribed to decomposition of excited triplet state of naproxen ( 3 NP ∗ ) and self-sensitization effect involving 1 O 2 . The FA-mediated photodegradation was mainly attributed to 1 O 2 oxidation in aerated solution. These findings are important for assessing the competitive effects of humic substances on the photodegradation of pollutants under various conditions in natural waters. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Characterization and functional analysis of the MAL and MPH Loci for maltose utilization in some ale and lager yeast strains.

    PubMed

    Vidgren, Virve; Ruohonen, Laura; Londesborough, John

    2005-12-01

    Maltose and maltotriose are the major sugars in brewer's wort. Brewer's yeasts contain multiple genes for maltose transporters. It is not known which of these express functional transporters. We correlated maltose transport kinetics with the genotypes of some ale and lager yeasts. Maltose transport by two ale strains was strongly inhibited by other alpha-glucosides, suggesting the use of broad substrate specificity transporters, such as Agt1p. Maltose transport by three lager strains was weakly inhibited by other alpha-glucosides, suggesting the use of narrow substrate specificity transporters. Hybridization studies showed that all five strains contained complete MAL1, MAL2, MAL3, and MAL4 loci, except for one ale strain, which lacked a MAL2 locus. All five strains also contained both AGT1 (coding a broad specificity alpha-glucoside transporter) and MAL11 alleles. MPH genes (maltose permease homologues) were present in the lager but not in the ale strains. During growth on maltose, the lager strains expressed AGT1 at low levels and MALx1 genes at high levels, whereas the ale strains expressed AGT1 at high levels and MALx1 genes at low levels. MPHx expression was negligible in all strains. The AGT1 sequences from the ale strains encoded full-length (616 amino acid) polypeptides, but those from both sequenced lager strains encoded truncated (394 amino acid) polypeptides that are unlikely to be functional transporters. Thus, despite the apparently similar genotypes of these ale and lager strains revealed by hybridization, maltose is predominantly carried by AGT1-encoded transporters in the ale strains and by MALx1-encoded transporters in the lager strains.

  13. Design, development, and optimization of polymeric based-colonic drug delivery system of naproxen.

    PubMed

    Sharma, Pooja; Chawla, Anuj; Pawar, Pravin

    2013-01-01

    The aim of present investigation deals with the development of time-dependent and pH sensitive press-coated tablets for colon specific drug delivery of naproxen. The core tablets were prepared by wet granulation method then press coated with hydroxypropyl cellulose (HPC) or Eudragit RSPO : RLPO mixture and further coated with Eudragit S-100 by dip immerse method. The in vitro drug release study was conducted in different dissolution media such as pH 1.2, 6.8, and 7.4 with or without rat caecal content to simulate GIT conditions. Surface morphology and cross-sectional view of the tablets were visualized by scanning electron microscopy (SEM). All prepared batches were in compliance with the pharmacopoeial standards. The tablets which are compression coated with HPC followed by Eudragit S-100 coated showed highest in vitro drug release of 98.10% in presence of rat caecal content. The SEM of tablets suggested that the number of pores got increased in pH 7.4 medium followed by dissolution of coating layer. The tablets coat erosion study suggested that the lag time depends upon the coating concentrations of polymers. A time-dependent hydrophilic polymer and pH sensitive polymer based press-coated tablets of naproxen were promising delivery for colon targeting.

  14. The effect of hydroxyapatite in biopolymer-based scaffolds on release of naproxen sodium.

    PubMed

    Asadian-Ardakani, Vahid; Saber-Samandari, Samaneh; Saber-Samandari, Saeed

    2016-12-01

    A scaffold capable of controlling drug release is highly desirable for bone tissue engineering. The objective of this study was to develop and characterize a highly porous biodegradable scaffold and evaluate the kinetic release behavior for the application of anti-inflammatory drug delivery. Porous scaffolds consisting of chitosan, poly(acrylic acid), and nano-hydroxyapatite were prepared using the freeze-drying method. The nanocomposite scaffolds were characterized for structure, pore size, porosity, and mechanical properties. The nanocomposite scaffolds were tested and characterized using Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy-dispersive analysis of X-ray (EDS), X-ray diffraction (XRD) analysis, and tensile test instrument. The results showed that the pores of the scaffolds were interconnected, and their sizes ranged from 145 µm to 213 μm. The mechanical properties were found close to those of trabecular bone of the same density. The ability of the scaffolds to deliver naproxen sodium as a model drug in vitro was investigated. The release profile of naproxen sodium was measured in a phosphate-buffered saline solution by a ultra-violet spectrophotometer that was controlled by the Fickian diffusion mechanism. These results indicated that the chitosan-graft-poly(acrylic acid)/nano-hydroxyapatite scaffold may be a promising biomedical scaffold for clinical use in bone tissue engineering with a potential for drug delivery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2992-3003, 2016. © 2016 Wiley Periodicals, Inc.

  15. Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin.

    PubMed

    Beyer, Andreas; Grohganz, Holger; Löbmann, Korbinian; Rades, Thomas; Leopold, Claudia S

    2015-10-27

    To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization behavior of co-amorphous systems are however limited to qualitative evaluations based on the corresponding X-ray powder diffractograms. Therefore, the objective of the study was to develop a quantification model based on X-ray powder diffractometry (XRPD), followed by a multivariate partial least squares regression approach that enables the simultaneous determination of up to four solid state fractions: crystalline naproxen, γ-indomethacin, α-indomethacin as well as co-amorphous naproxen-indomethacin. For this purpose, a calibration set that covers the whole range of possible combinations of the four components was prepared and analyzed by XRPD. In order to test the model performances, leave-one-out cross validation was performed and revealed root mean square errors of validation between 3.11% and 3.45% for the crystalline molar fractions and 5.57% for the co-amorphous molar fraction. In summary, even four solid state phases, involving one co-amorphous phase, can be quantified with this XRPD data-based approach.

  16. Design, Development, and Optimization of Polymeric Based-Colonic Drug Delivery System of Naproxen

    PubMed Central

    Sharma, Pooja; Chawla, Anuj; Pawar, Pravin

    2013-01-01

    The aim of present investigation deals with the development of time-dependent and pH sensitive press-coated tablets for colon specific drug delivery of naproxen. The core tablets were prepared by wet granulation method then press coated with hydroxypropyl cellulose (HPC) or Eudragit RSPO : RLPO mixture and further coated with Eudragit S-100 by dip immerse method. The in vitro drug release study was conducted in different dissolution media such as pH 1.2, 6.8, and 7.4 with or without rat caecal content to simulate GIT conditions. Surface morphology and cross-sectional view of the tablets were visualized by scanning electron microscopy (SEM). All prepared batches were in compliance with the pharmacopoeial standards. The tablets which are compression coated with HPC followed by Eudragit S-100 coated showed highest in vitro drug release of 98.10% in presence of rat caecal content. The SEM of tablets suggested that the number of pores got increased in pH 7.4 medium followed by dissolution of coating layer. The tablets coat erosion study suggested that the lag time depends upon the coating concentrations of polymers. A time-dependent hydrophilic polymer and pH sensitive polymer based press-coated tablets of naproxen were promising delivery for colon targeting. PMID:24198725

  17. Performance evaluation of a mobile satellite system modem using an ALE method

    NASA Technical Reports Server (NTRS)

    Ohsawa, Tomoki; Iwasaki, Motoya

    1990-01-01

    Experimental performance of a newly designed demodulation concept is presented. This concept applies an Adaptive Line Enhancer (ALE) to a carrier recovery circuit, which makes pull-in time significantly shorter in noisy and large carrier offset conditions. This new demodulation concept was actually developed as an INMARSAT standard-C modem, and was evaluated. On a performance evaluation, 50 symbol pull-in time is confirmed under 4 dB Eb/No condition.

  18. Naproxen effects on brain response to painful pressure stimulation in patients with knee osteoarthritis: a double-blind, randomized, placebo-controlled, single-dose study.

    PubMed

    Giménez, Mónica; Pujol, Jesús; Ali, Zahid; López-Solà, Marina; Contreras-Rodríguez, Oren; Deus, Joan; Ortiz, Héctor; Soriano-Mas, Carles; Llorente-Onaindia, Jone; Monfort, Jordi

    2014-11-01

    The aim of our study was to investigate the effects of naproxen, an antiinflammatory analgesic drug, on brain response to painful stimulation on the affected knee in chronic osteoarthritis (OA) using functional magnetic resonance imaging (fMRI) in a double-blind, placebo-controlled study. A sample of 25 patients with knee OA received naproxen (500 mg), placebo, or no treatment in 3 separate sessions in a randomized manner. Pressure stimulation was applied to the medial articular interline of the knee during the fMRI pain sequence. We evaluated subjective pain ratings at every session and their association with brain responses to pain. An fMRI control paradigm was included to discard global brain vascular effects of naproxen. We found brain activation reductions under naproxen compared to no treatment in different cortical and subcortical core pain processing regions (p≤0.001). Compared to placebo, naproxen triggered an attenuation of amygdala activation (p=0.001). Placebo extended its attenuation effects beyond the classical pain processing network (p≤0.001). Subjective pain scores during the fMRI painful task differed between naproxen and no treatment (p=0.037). Activation attenuation under naproxen in different regions (i.e., ventral brain, cingulate gyrus) was accompanied by an improvement in the subjective pain complaints (p≤0.002). Naproxen effectively reduces pain-related brain responses involving different regions and the attenuation is related to subjective pain changes. Our current work yields further support to the utility of fMRI to objectify the acute analgesic effects of a single naproxen dose in patients affected by knee OA. The trial was registered at the EuropeanClinicalTrials Database, "EudraCT Number 2008-004501-33".

  19. Compatible, energy conserving, bounds preserving remap of hydrodynamic fields for an extended ALE scheme

    NASA Astrophysics Data System (ADS)

    Burton, D. E.; Morgan, N. R.; Charest, M. R. J.; Kenamond, M. A.; Fung, J.

    2018-02-01

    From the very origins of numerical hydrodynamics in the Lagrangian work of von Neumann and Richtmyer [83], the issue of total energy conservation as well as entropy production has been problematic. Because of well known problems with mesh deformation, Lagrangian schemes have evolved into Arbitrary Lagrangian-Eulerian (ALE) methods [39] that combine the best properties of Lagrangian and Eulerian methods. Energy issues have persisted for this class of methods. We believe that fundamental issues of energy conservation and entropy production in ALE require further examination. The context of the paper is an ALE scheme that is extended in the sense that it permits cyclic or periodic remap of data between grids of the same or differing connectivity. The principal design goals for a remap method then consist of total energy conservation, bounded internal energy, and compatibility of kinetic energy and momentum. We also have secondary objectives of limiting velocity and stress in a non-directional manner, keeping primitive variables monotone, and providing a higher than second order reconstruction of remapped variables. In particular, the new contributions fall into three categories associated with: energy conservation and entropy production, reconstruction and bounds preservation of scalar and tensor fields, and conservative remap of nonlinear fields. The paper presents a derivation of the methods, details of implementation, and numerical results for a number of test problems. The methods requires volume integration of polynomial functions in polytopal cells with planar facets, and the requisite expressions are derived for arbitrary order.

  20. Microbial diversity and metabolite composition of Belgian red-brown acidic ales.

    PubMed

    Snauwaert, Isabel; Roels, Sanne P; Van Nieuwerburg, Filip; Van Landschoot, Anita; De Vuyst, Luc; Vandamme, Peter

    2016-03-16

    Belgian red-brown acidic ales are sour and alcoholic fermented beers, which are produced by mixed-culture fermentation and blending. The brews are aged in oak barrels for about two years, after which mature beer is blended with young, non-aged beer to obtain the end-products. The present study evaluated the microbial community diversity of Belgian red-brown acidic ales at the end of the maturation phase of three subsequent brews of three different breweries. The microbial diversity was compared with the metabolite composition of the brews at the end of the maturation phase. Therefore, mature brew samples were subjected to 454 pyrosequencing of the 16S rRNA gene (bacteria) and the internal transcribed spacer region (yeasts) and a broad range of metabolites was quantified. The most important microbial species present in the Belgian red-brown acidic ales investigated were Pediococcus damnosus, Dekkera bruxellensis, and Acetobacter pasteurianus. In addition, this culture-independent analysis revealed operational taxonomic units that were assigned to an unclassified fungal community member, Candida, and Lactobacillus. The main metabolites present in the brew samples were L-lactic acid, D-lactic acid, and ethanol, whereas acetic acid was produced in lower quantities. The most prevailing aroma compounds were ethyl acetate, isoamyl acetate, ethyl hexanoate, and ethyl octanoate, which might be of impact on the aroma of the end-products. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Compatible, energy conserving, bounds preserving remap of hydrodynamic fields for an extended ALE scheme

    DOE PAGES

    Burton, Donald E.; Morgan, Nathaniel Ray; Charest, Marc Robert Joseph; ...

    2017-11-22

    From the very origins of numerical hydrodynamics in the Lagrangian work of von Neumann and Richtmyer [83], the issue of total energy conservation as well as entropy production has been problematic. Because of well known problems with mesh deformation, Lagrangian schemes have evolved into Arbitrary Lagrangian–Eulerian (ALE) methods [39] that combine the best properties of Lagrangian and Eulerian methods. Energy issues have persisted for this class of methods. We believe that fundamental issues of energy conservation and entropy production in ALE require further examination. The context of the paper is an ALE scheme that is extended in the sense thatmore » it permits cyclic or periodic remap of data between grids of the same or differing connectivity. The principal design goals for a remap method then consist of total energy conservation, bounded internal energy, and compatibility of kinetic energy and momentum. We also have secondary objectives of limiting velocity and stress in a non-directional manner, keeping primitive variables monotone, and providing a higher than second order reconstruction of remapped variables. Particularly, the new contributions fall into three categories associated with: energy conservation and entropy production, reconstruction and bounds preservation of scalar and tensor fields, and conservative remap of nonlinear fields. Our paper presents a derivation of the methods, details of implementation, and numerical results for a number of test problems. The methods requires volume integration of polynomial functions in polytopal cells with planar facets, and the requisite expressions are derived for arbitrary order.« less

  2. Magmatic architecture within a rift segment: Articulate axial magma storage at Erta Ale volcano, Ethiopia

    NASA Astrophysics Data System (ADS)

    Xu, Wenbin; Rivalta, Eleonora; Li, Xing

    2017-10-01

    Understanding the magmatic systems beneath rift volcanoes provides insights into the deeper processes associated with rift architecture and development. At the slow spreading Erta Ale segment (Afar, Ethiopia) transition from continental rifting to seafloor spreading is ongoing on land. A lava lake has been documented since the twentieth century at the summit of the Erta Ale volcano and acts as an indicator of the pressure of its magma reservoir. However, the structure of the plumbing system of the volcano feeding such persistent active lava lake and the mechanisms controlling the architecture of magma storage remain unclear. Here, we combine high-resolution satellite optical imagery and radar interferometry (InSAR) to infer the shape, location and orientation of the conduits feeding the 2017 Erta Ale eruption. We show that the lava lake was rooted in a vertical dike-shaped reservoir that had been inflating prior to the eruption. The magma was subsequently transferred into a shallower feeder dike. We also find a shallow, horizontal magma lens elongated along axis inflating beneath the volcano during the later period of the eruption. Edifice stress modeling suggests the hydraulically connected system of horizontal and vertical thin magmatic bodies able to open and close are arranged spatially according to stresses induced by loading and unloading due to topographic changes. Our combined approach may provide new constraints on the organization of magma plumbing systems beneath volcanoes in continental and marine settings.

  3. Ecological perspectives of land use history: The Arid Lands Ecology (ALE) Reserve

    SciTech Connect

    Hinds, N R; Rogers, L E

    The objective of this study was to gather information on the land use history of the Arid Land Ecology (ALE) Reserve so that current ecological research could be placed within a historical perspective. The data were gathered in the early 1980s by interviewing former users of the land and from previously published research (where available). Interviews with former land users of the ALE Reserve in Benton County, Washington, revealed that major land uses from 1880 to 1940 were homesteading, grazing, oil/gas production, and road building. Land use practices associated with grazing and homesteading have left the greatest impact on themore » landscape. Disturbed sites where succession is characterized by non-native species, plots where sagebrush was railed away, and sheep trails are major indications today of past land uses. Recent estimates of annual bunchgrass production do ALE do not support the widespread belief that bunchgrass were more productive during the homesteading era, though the invasion of cheatgrass (Bromus tectorum), Jim Hill mustard (Sisymbrium altissium), and other European alien plant species has altered pre-settlement succession patterns. 15 refs., 6 figs., 1 tab.« less

  4. Compatible, energy conserving, bounds preserving remap of hydrodynamic fields for an extended ALE scheme

    SciTech Connect

    Burton, Donald E.; Morgan, Nathaniel Ray; Charest, Marc Robert Joseph

    From the very origins of numerical hydrodynamics in the Lagrangian work of von Neumann and Richtmyer [83], the issue of total energy conservation as well as entropy production has been problematic. Because of well known problems with mesh deformation, Lagrangian schemes have evolved into Arbitrary Lagrangian–Eulerian (ALE) methods [39] that combine the best properties of Lagrangian and Eulerian methods. Energy issues have persisted for this class of methods. We believe that fundamental issues of energy conservation and entropy production in ALE require further examination. The context of the paper is an ALE scheme that is extended in the sense thatmore » it permits cyclic or periodic remap of data between grids of the same or differing connectivity. The principal design goals for a remap method then consist of total energy conservation, bounded internal energy, and compatibility of kinetic energy and momentum. We also have secondary objectives of limiting velocity and stress in a non-directional manner, keeping primitive variables monotone, and providing a higher than second order reconstruction of remapped variables. Particularly, the new contributions fall into three categories associated with: energy conservation and entropy production, reconstruction and bounds preservation of scalar and tensor fields, and conservative remap of nonlinear fields. Our paper presents a derivation of the methods, details of implementation, and numerical results for a number of test problems. The methods requires volume integration of polynomial functions in polytopal cells with planar facets, and the requisite expressions are derived for arbitrary order.« less

  5. A germination bioassay as a toxicological screening system for studying the effects of potential prodrugs of naproxen.

    PubMed

    Gonzalez-de la Parra, M; Ramos-Mundo, C; Jimenez-Estrada, M; Ponce-de Leon, C; Castillo, R; Tejeda, V; Cuevas, K G; Enriquez, R G

    1998-01-01

    A germination bioassay with radish (Raphanus sativus L.) seeds was developed as a toxicological screening system for assessing the effects of new potential prodrugs of naproxen, as an alternative to animals and animal cell toxicity screens. Both enantiomers of naproxen (6-methoxy-α-methyl-2-naphthaleneacetic acid) and naproxol (6-methoxy-β-2-naphthaleneethanol), and their racemic mixtures, inhibited the radicle growth of R. sativus at a concentration of 1mM, while only (R)-(+ )-naproxol and racemic naproxol inhibited the hypocotyl growth of R. sativus at the same concentration. Four novel combinatorial esters, naproxen naproxyl esters (6-methoxy-β-methyl-2-naphthaleneethyl 6-methoxy-α-methyl-2-naphthaleneacetate), resulting from the combinatorial chemistry of the esterification reaction between naproxen and naproxol, were synthesised and then tested in the germination bioassay, at a concentration of 0.5mM. It was found that they did not inhibit either the radicle or the hypocotyl growth of R. sativus. 1998 FRAME.

  6. A Sulfated-Polysaccharide Fraction from Seaweed Gracilaria birdiae Prevents Naproxen-Induced Gastrointestinal Damage in Rats

    PubMed Central

    Silva, Renan O.; Santana, Ana Paula M.; Carvalho, Nathalia S.; Bezerra, Talita S.; Oliveira, Camila B.; Damasceno, Samara R. B.; Chaves, Luciano S.; Freitas, Ana Lúcia P.; Soares, Pedro M. G.; Souza, Marcellus H. L. P.; Barbosa, André Luiz R.; Medeiros, Jand-Venes R.

    2012-01-01

    Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group—vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation. PMID:23342384

  7. A sulfated-polysaccharide fraction from seaweed Gracilaria birdiae prevents naproxen-induced gastrointestinal damage in rats.

    PubMed

    Silva, Renan O; Santana, Ana Paula M; Carvalho, Nathalia S; Bezerra, Talita S; Oliveira, Camila B; Damasceno, Samara R B; Chaves, Luciano S; Freitas, Ana Lúcia P; Soares, Pedro M G; Souza, Marcellus H L P; Barbosa, André Luiz R; Medeiros, Jand-Venes R

    2012-12-01

    Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group-vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation.

  8. Comparison of oral oxycodone and naproxen in soft tissue injury pain control: a double-blind randomized clinical trial.

    PubMed

    Fathi, Marzieh; Zare, Mohammad Amin; Bahmani, Hamid Reza; Zehtabchi, Shahriar

    2015-09-01

    This randomized clinical trial compares the efficacy and safety of oral oxycodone (an oral opioid) with naproxen (a nonsteroidal anti-inflammatory drug) in acute pain control in patients with soft tissue injury. It also evaluates the need for additional doses of analgesics in the first 24 hours of discharge from emergency department (ED). Adult (>18 years old) patients with soft tissue injuries were enrolled in a teaching urban ED. Subjects were randomly allocated to receive a single dose of oral oxycodone (5 mg) or oral naproxen (250 mg). Pain scores and drugs' adverse effects were assessed before, 30 minutes, and 60 minutes after medication. efficacy in pain control (reduction in pain scale >2 points) and safety (rate of side effects). The need for additional pain medication after discharge was assessed by follow-up phone call 24 hours after discharge. A total of 150 patients were enrolled. Pain scores were similar in oxycodone vs naproxen groups before (6.21 ± 0.9 in vs 6.0 ± 1.0), 30 minutes (4.5 ± 1.4 vs 4.4 ± 1.2), and 60 minutes (2.5 ± 1.3 in vs 2.6 ± 1.3) after medication, respectively. Twelve (16.0%) patients in oral oxycodone group and 5 (6.6%) patients in naproxen group needed more analgesics in first 24 hours after ED discharge. Adverse effects were more common in oxycodone group (statistically significant difference). The most common adverse effects in oxycodone group were nausea, (13.3%); vomiting, (8.0%); dizziness, (5.3%); drowsiness, 3 (4.0%); and pruritis, (2.7%). Oral oxycodone is as effective as naproxen in soft tissue injury pain control but has a less favorable safety profile. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The Risk of Major NSAID Toxicity with Celecoxib, Ibuprofen, or Naproxen: A Secondary Analysis of the PRECISION Trial.

    PubMed

    Solomon, Daniel H; Husni, M Elaine; Libby, Peter A; Yeomans, Neville D; Lincoff, A Michael; Lϋscher, Thomas F; Menon, Venu; Brennan, Danielle M; Wisniewski, Lisa M; Nissen, Steven E; Borer, Jeffrey S

    2017-12-01

    The relative safety of long-term use of nonsteroidal anti-inflammatory drugs is unclear. Patients and providers are interested in an integrated view of risk . We examined the risk of major nonsteroidal anti-inflammatory drug toxicity in the PRECISION trial. We conducted a post hoc analysis of a double-blind, randomized, controlled, multicenter trial enrolling 24,081 patients with osteoarthritis or rheumatoid arthritis at moderate or high cardiovascular risk. Patients were randomized to receive celecoxib 100 to 200 mg twice daily, ibuprofen 600 to 800 mg thrice daily, or naproxen 375 to 500 mg twice daily. All patients were provided with a proton pump inhibitor. The outcome was major nonsteroidal anti-inflammatory drug toxicity, including time to first occurrence of major adverse cardiovascular events, important gastrointestinal events, renal events, and all-cause mortality. During follow-up, 4.1% of subjects sustained any major toxicity in the celecoxib arm, 4.8% in the naproxen arm, and 5.3% in the ibuprofen arm. Analyses adjusted for aspirin use and geographic region found that subjects in the naproxen arm had a 20% (95% CI 4-39) higher risk of major toxicity than celecoxib users and that 38% (95% CI 19-59) higher risk. These risks translate into numbers needed to harm of 135 (95% CI, 72-971) for naproxen and 82 (95% CI, 53-173) for ibuprofen, both compared with celecoxib. Among patients with symptomatic arthritis who had moderate to high risk of cardiovascular events, approximately 1 in 20 experienced a major toxicity over 1 to 2 years. Patients using naproxen or ibuprofen experienced significantly higher risk of major toxicity than those using celecoxib. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Mimicking natural systems: Changes in behavior as a result of dynamic exposure to naproxen.

    PubMed

    Neal, Alexandra E; Moore, Paul A

    2017-01-01

    Animals living in aquatic habitats regularly encounter anthropogenic chemical pollution. Typically, the toxicity of a chemical toxicant is determined by the median lethal concentration (LC 50 ) through a static exposure test. However, LC 50 values and static tests do not provide an accurate representation of exposure to pollutants within natural stream systems. In their native habitats, animals experience exposure as a fluctuating concentration due to turbulent mixing, temporal variations of contamination (seasonal inputs), and contaminant input type (point vs. non-point). Research has shown that turbulent environments produce exposures with a high degree of fluctuation in frequency, duration, and intensity. In order to more effectively evaluate the effects of pollutants, we created a dynamic exposure paradigm, utilizing both flow and substrate within a small mesocosm. A commonly used pharmaceutical, naproxen, was used as the toxicant and female crayfish (Orconectes virilis) as the target organism to investigate changes in fighting behavior as a result of dynamic exposure. Crayfish underwent either a 23h long static or a dynamic exposure to naproxen. Following exposure, the target crayfish and an unexposed size matched opponent underwent a 15min fight trial. These fight trials were recorded and later analyzed using a standard ethogram. Results indicate that exposure to sublethal concentrations of naproxen, in both static and flowing conditions, negatively impact aggressive behavior. Results also indicate that a dynamic exposure paradigm has a greater negative impact on behavior than a static exposure. Turbulence and habitat structure play important roles in shaping chemical exposure. Future research should incorporate features of dynamic chemical exposure in order to form a more comprehensive image of chemical exposure and predict the resulting sublethal effects from exposure. Possible techniques for assessment include utilizing flow-through experimental set-ups in

  11. Modeling Combined Immunosuppressive and Anti-inflammatory Effects of Dexamethasone and Naproxen in Rats Predicts the Steroid-Sparing Potential of Naproxen.

    PubMed

    Li, Xiaonan; DuBois, Debra C; Song, Dawei; Almon, Richard R; Jusko, William J; Chen, Xijing

    2017-07-01

    Dexamethasone (DEX), a widely prescribed corticosteroid, has long been the cornerstone of the treatment of inflammation and immunologic dysfunctions in rheumatoid arthritis. Corticosteroids are frequently used in combination with other antirheumatic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs to mitigate disease symptoms and minimize unwanted effects. We explored the steroid dose-sparing potential of the NSAID naproxen (NPX) with in vitro and in vivo studies. The single and joint suppressive effects of DEX and NPX on the in vitro mitogen-induced proliferation of T lymphocytes in blood and their anti-inflammatory actions on paw edema were investigated in female and male Lewis rats with collagen-induced arthritis (CIA). As expected, DEX was far more potent than NPX in these systems. Mathematical models incorporating an interaction term ψ were applied to quantitatively assess the nature and intensity of pharmacodynamic interactions between DEX and NPX. Modest synergistic effects of the two drugs were found in suppressing the mitogenic response of T lymphocytes. A pharmacokinetic/pharmacodynamic/disease progression model integrating dual drug inhibition quantitatively described the pharmacokinetics, time-course of single and joint anti-inflammatory effects (paw edema), and sex differences in CIA rats, and indicated additive effects of DEX and NPX. Further model simulations demonstrated the promising steroid-sparing potential of NPX in CIA rats, with the beneficial effects of the combination therapy more likely in males than females. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Naproxen Induces Type X Collagen Expression in Human Bone-Marrow-Derived Mesenchymal Stem Cells Through the Upregulation of 5-Lipoxygenase

    PubMed Central

    Alaseem, Abdulrahman M.; Madiraju, Padma; Aldebeyan, Sultan A.; Noorwali, Hussain; Antoniou, John

    2015-01-01

    Several studies have shown that type X collagen (COL X), a marker of late-stage chondrocyte hypertrophy, is expressed in mesenchymal stem cells (MSCs) from osteoarthritis (OA) patients. We recently found that Naproxen, but not other nonsteroidal anti-inflammatory drugs (NSAIDs) (Ibuprofen, Celebrex, Diclofenac), can induce type X collagen gene (COL10A1) expression in bone-marrow-derived MSCs from healthy and OA donors. In this study we determined the effect of Naproxen on COL X protein expression and investigated the intracellular signaling pathways that mediate Naproxen-induced COL10A1 expression in normal and OA hMSCs. MSCs of OA patients were isolated from aspirates from the intramedullary canal of donors (50–80 years of age) undergoing hip replacement surgery for OA and were treated with or without Naproxen (100 μg/mL). Protein expression and phosphorylation were determined by immunoblotting using specific antibodies (COL X, p38 mitogen-activated protein kinase [p38], phosphorylated-p38, c-Jun N-terminal kinase [JNK], phosphorylated-JNK, extracellular signal-regulated kinase [ERK], and phosphorylated-ERK). Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to determine the expression of COL10A1 and Runt-related transcription factor 2 gene (Runx2). Our results show that Naproxen significantly stimulated COL X protein expression after 72 h of exposure both in normal and OA hMSCs. The basal phosphorylation of mitogen-activated protein kinases (MAPKs) (ERK, JNK, and p38) in OA hMSCs was significantly higher than in normal. Naproxen significantly increased the MAPK phosphorylation in normal and OA hMSCs. NSAID cellular effects include cyclooxygenase, 5-lipoxygenase, and p38 MAPK signaling pathways. To investigate the involvement of these pathways in the Naproxen-induced COL10A1 expression, we incubated normal and OA hMSCs with Naproxen with and without inhibitors of ERK (U0126), JNK (BI-78D3), p38 (SB203580), and 5-lipoxygenase

  13. Low doses of tizanidine synergize the anti-nociceptive and anti-inflammatory effects of ketorolac or naproxen while reducing of side effects.

    PubMed

    Patiño-Camacho, Selene I; Déciga Campos, Myrna; Beltrán-Villalobos, Karla; Castro-Vidal, Dalia A; Montiel-Ruiz, Rosa M; Flores-Murrieta, Francisco J

    2017-06-15

    The aim of the present study was to determine whether tizanidine, an alpha2-adrenoceptor agonist, is able to increase the anti-inflammatory and anti-nociceptive effects of naproxen and ketorolac with a low incidence of gastric injury and spontaneous activity in rats. The anti-inflammatory effect was assayed in a carrageenan test, and oral administration of tizanidine (ED 40 =0.94±0.2mg/kg), naproxen (ED 40 =3.18±0.4mg/kg), and ketorolac (ED 40 =16.4±1.9mg/kg) showed a dose-dependent effect on inflammation. The anti-nociceptive effect was assayed in the formalin test, and administration of tizanidine (ED 40 =0.39±0.06mg/kg, p.o.), naproxen (ED 40 =33.9±3.9mg/kg, p.o.) or ketorolac (ED 40 =6.49±1mg/kg, p.o.) each showed a dose-dependent anti-nociceptive effect. The effects of combinations of tizanidine/naproxen and tizanidine/ketorolac were determined considering their ED 40 at a rate of 1:1. Additionally, the tizanidine/naproxen and tizanidine/ketorolac combinations showed anti-inflammatory and anti-nociceptive effects. The tizanidine/ketorolac combination was more potent than tizanidine/naproxen, in both inflammatory (interaction index=0.03 tizanidine/ketorolac and 0.07 tizanidine/naproxen) and nociceptive (interaction index=0.005 tizanidine/ketorolac and 0.01 tizanidine/naproxen) processes. In both cases, tizanidine improved naproxen and ketorolac gastrointestinal tolerability by 50%. Furthermore, co-administration of tizanidine with naproxen or ketorolac did not modify the spontaneous activity in the same way as individual tizanidine administration. Considering that tizanidine increases the anti-inflammatory and anti-nociceptive effects of naproxen or ketorolac, with an increase in gastric tolerability, tizanidine could provide therapeutic advantages in the clinical treatment of inflammation and pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Fluorescent high-performance liquid chromatographic analysis of vigabatrin enantiomers after derivatizing with naproxen acyl chloride.

    PubMed

    Hsieh, Chun-Yu; Wang, Shing-Yaw; Kwan, Aij-Lie; Wu, Hsin-Lung

    2008-01-18

    Vigabatrin is widely used as an anticonvulsant in the treatment of seizures. Vigabatrin is usually supplied as racemate in formulation, but only the (S)-(+)-enantiomer of vigabatrin is pharmacologically active. A simple and sensitive liquid chromatographic method is described for the separation and quantification of vigabatrin enantiomers. The method is based on derivatizing racemic vigabatrin with a fluorescent chiral reagent (naproxen acyl chloride). The resulting diastereomeric derivatives are highly responsive to a fluorimetric detector (lambda(ex)=230 nm, lambda(em)=350 nm). The lower quantitation limit of the method is attainable at 25 nM for (S)-(+)-vigabatrin or (R)-(-)-vigabatrin with a detection limit of about 2.5 nM (S/N=3 with 10 microl injected). Application of the method to the analysis of vigabatrin in serum of dosed patients proved feasible.

  15. Time-resolved fluorescence study of exciplex formation in diastereomeric naproxen-pyrrolidine dyads.

    PubMed

    Khramtsova, Ekaterina A; Plyusnin, Viktor F; Magin, Ilya M; Kruppa, Alexander I; Polyakov, Nikolay E; Leshina, Tatyana V; Nuin, Edurne; Marin, M Luisa; Miranda, Miguel A

    2013-12-19

    The influence of chirality on the elementary processes triggered by excitation of the (S,S)- and (R,S)- diastereoisomers of naproxen-pyrrolidine (NPX-Pyr) dyads has been studied by time-resolved fluorescence in acetonitrile-benzene mixtures. In these systems, the quenching of the (1)NPX*-Pyr singlet excited state occurs through electron transfer and exciplex formation. Fluorescence lifetimes and quantum yields revealed a significant difference (around 20%) between the (S,S)- and (R,S)- diastereomers. In addition, the quantum yields of exciplexes differed by a factor of 2 regardless of solvent polarity. This allows us to suggest a similar influence of the chiral centers on the local charge transfer resulting in exciplex and full charge separation that leads to ion-biradicals. A simplified scheme is proposed to estimate a set of rate constant values (k1-k5) for the elementary stages in each solvent system.

  16. Adsorptive removal of naproxen and clofibric acid from water using metal-organic frameworks.

    PubMed

    Hasan, Zubair; Jeon, Jaewoo; Jhung, Sung Hwa

    2012-03-30

    Adsorptive removal of naproxen and clofibric acid, two typical PPCPs (pharmaceuticals and personal care products), has been studied using metal-organic frameworks (MOFs) for the first time. The removal efficiency decreases in the order of MIL-101>MIL-100-Fe>activated carbon both in adsorption rate and adsorption capacity. The adsorption kinetics and capacity of PPCPs generally depend on the average pore size and surface area (or pore volume), respectively, of the adsorbents. The adsorption mechanism may be explained with a simple electrostatic interaction between PPCPs and the adsorbent. Finally, it can be suggested that MOFs having high porosity and large pore size can be potential adsorbents to remove harmful PPCPs in contaminated water. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Microbial transformation of pharmaceuticals naproxen, bisoprolol, and diclofenac in aerobic and anaerobic environments.

    PubMed

    Lahti, Marja; Oikari, Aimo

    2011-08-01

    Although biotransformation is generally considered to be the main process by which to remove pharmaceuticals, both in sewage treatment plants and in aquatic environments, quantitative information on specific compounds is scarce. In this study, the transformations of diclofenac (DCF), naproxen (NPX), and bisoprolol (BSP) were studied under aerobic and anaerobic conditions using inocula taken from activated and digested sludge processes, respectively. Whereas concentration decays were monitored by LC-tandem mass spectrometry, oxygen consumption and methane production were used for the evaluation of the performance of overall conditions. DCF was recalcitrant against both aerobic and anaerobic biotransformation. More than one third of the BSP disappeared under aerobic conditions, whereas only 14% was anaerobically biotransformed in 161 days. Under aerobic conditions, complete removal of NPX was evident within 14 days, but anaerobic transformation was also efficient. Formation of 6-O-desmethylnaproxen, a previously reported aerobic metabolite, was also detected under anaerobic conditions and persisted for 161 days.

  18. Prevention of chemically induced urinary bladder cancers by naproxen: protocols to reduce gastric toxicity in humans do not alter preventive efficacy.

    PubMed

    Lubet, Ronald A; Scheiman, James M; Bode, Ann; White, Jonathan; Minasian, Lori; Juliana, M Margaret; Boring, Daniel L; Steele, Vernon E; Grubbs, Clinton J

    2015-04-01

    The COX inhibitors (NSAID/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2-specific inhibitors have progressed to clinical trials and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular effects. Certain NSAIDs (e.g., naproxen) have a good cardiac profile, but can cause gastric toxicity. The present study examined protocols to reduce this toxicity of naproxen. Female Fischer-344 rats were treated weekly with the urinary bladder-specific carcinogen hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with NPX (40 mg/kg body weight/day, gavage) or with the proton pump inhibitor omeprazole (4.0 mg/kg body weight/day) either singly or in combination beginning 2 weeks after the final OH-BBN. OH-BBN-treated rats, 96% developed urinary bladder cancers. While omeprazole alone was ineffective (97% cancers), naproxen alone or combined with omeprazole-prevented cancers, yielding 27 and 35% cancers, respectively. In a separate study, OH-BBN -: treated rats were administered naproxen: (A) daily, (B) 1 week daily naproxen/1week vehicle, (C) 3 weeks daily naproxen/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN treatment. In the intermittent dosing study, protocol A, B, C, and D resulted in palpable cancers in 27%, 22%, 19%, and 96% of rats (P < 0.01). Short-term naproxen treatment increased apoptosis, but did not alter proliferation in the urinary bladder cancers. Two different protocols that should decrease the gastric toxicity of NSAIDs in humans did not alter chemopreventive efficacy. This should encourage the use of NSAIDs (e.g., naproxen) in clinical prevention trials. ©2015 American Association for Cancer Research.

  19. Synthesis and antinociceptive evaluation of bioisosteres and hybrids of naproxen, ibuprofen and paracetamol.

    PubMed

    González-Trujano, María Eva; Uribe-Figueroa, Gerardo; Hidalgo-Figueroa, Sergio; Martínez, Ana Laura; Déciga-Campos, Myrna; Navarrete-Vazquez, Gabriel

    2018-05-01

    The aim of this work was to design, synthesize and characterize the potential anti-nociceptive and anti-inflammatory activities of a new series of bioisosteres and hybrids from known non-steroidal anti-inflammatory drugs (NSAIDs). The compounds 4-(acetylamino)phenyl (2S)-2-(6-methoxy-2-naphthyl)propanoate (GUF-1) and 4-(acetylamino)phenyl 2-(R,S)-(4-isobutylphenyl)propanoate (GUF-2) were synthesized as hybrids (also known as heterodimers); whereas those named 2-(R,S)-(4-isobutylphenyl)-N-1H-tetrazol-5-ylpropanamide (GUF-3), (2S)-2-(6-methoxy-2-naphthyl)-N-1H-tetrazol-5-ylpropanamide (GUF-4), [2-(R,S)-N-hydroxy-2-[4-(2-methylpropyl)phenyl]propanamide] (GUF-5), and (2S)-N-hydroxy-2-(6-methoxy-2-naphthyl)propanamide (GUF-6) were synthesized as bioisosteres of the NSAIDs paracetamol, ibuprofen, and naproxen, respectively. All these compounds were characterized by spectroscopic and spectrometric analysis. Antinociceptive activity of GUF-1 to GUF-6 was evaluated using the formalin test in rats. Pharmacological responses of GUF-1, GUF-2 (hybrids), and GUF-5 (bioisostere) demonstrated significant antinociceptive effects; thus these compounds were assayed in an inflammation test like carrageenan-induced paw oedema in rats. Complete molecular docking of cyclooxygenase and the GUF-1 and GUF-2 hybrids showed high docking scores, compared to the reference drugs. Our data demonstrate that compounds GUF-1, GUF-2, and GUF-5 possesses antinociceptive and antiinflammatory activities resembling and improving those known for the traditional NSAIDs, paracetamol, naproxen and ibuprofen. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  20. Occurrence and behavior of the chiral anti-inflammatory drug naproxen in an aquatic environment.

    PubMed

    Suzuki, Toshinari; Kosugi, Yuki; Hosaka, Mitsugu; Nishimura, Tetsuji; Nakae, Dai

    2014-12-01

    The present study reports on the occurrence and chiral behavior of the anti-inflammatory drug (S)-naproxen (NAP)-(S)-2-(6-methoxynaphthalen-2-yl)propionic acid-in an aquatic environment under both field and laboratory conditions. In influents and effluents of sewage treatment plants (STPs) in the Tama River basin (Tokyo), (S)-NAP was detected at concentrations of 0.03 µg L(-1) to 0.43 µg L(-1) and 0.01 µg L(-1) to 0.11 µg L(-1), respectively. The concentrations of a major metabolite, 6-O-desmethyl NAP (DM-NAP) were up to 0.47 µg L(-1) and 0.56 µg L(-1) in influents and effluents, respectively. (R)-naproxen was not detected in STP influents, although it was present in effluents, and the enantiomeric faction (= S/[S + R]) of NAP ranged from 0.88 to 0.91. Under laboratory conditions with activated sludge from STPs, rapid degradation of (S)-NAP to DM-NAP and chiral inversion of (S)-NAP to (R)-NAP were observed. During river die-away experiments, degradation and chiral inversion of NAP were extremely slow. In addition, chiral inversion of (S)-NAP to (R)-NAP was not observed during photodegradation experiments. In the river receiving STP discharge, NAP and DM-NAP concentrations reached 0.08 µg L(-1) and 0.16 µg L(-1) , respectively. The enantiomeric faction of NAP in the river ranged from 0.84 to 0.98 and remained almost unchanged with the increasing contribution of rainfall to the river water. These results suggest that the absence and decrease of (R)-NAP in river waters could indicate the inflow of untreated sewage. E © 2014 SETAC.

  1. Reactive Melt Extrusion To Improve the Dissolution Performance and Physical Stability of Naproxen Amorphous Solid Dispersions.

    PubMed

    Liu, Xu; Zhou, Lin; Zhang, Feng

    2017-03-06

    The purpose of this study was to investigate the reaction between naproxen (NPX) and meglumine (MEG) at elevated temperature and to study the effect of this reaction on the physical stabilities and in vitro drug-release properties of melt-extruded naproxen amorphous solid dispersions (ASDs). Differential scanning calorimetry, hot-stage polarized light microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy analyses demonstrated that in situ salt formation with proton transfer between NPX and MEG occurred at elevated temperature during the melt extrusion process. The amorphous NPX-MEG salt was physically most stable when two components were present at a 1:1 molar ratio. Polymeric carriers, including povidone, copovidone, and SOLUPLUS, did not interfere with the reaction between NPX and MEG during melt extrusion. Compared to the traditional NPX ASDs consisting of NPX and polymer only, NPX-MEG ASDs were physically more stable and remained amorphous following four months storage at 40 °C and 75% RH (relative humidity). Based on nonsink dissolution testing and polarized light microscopy analyses, we concluded that the conventional NPX ASDs composed of NPX and polymers failed to improve the NPX dissolution rate due to the rapid recrystallization of NPX in contact with aqueous medium. The dissolution rate of NPX-MEG ASDs was two times greater than the corresponding physical mixtures and conventional NPX ASDs. This study demonstrated that the acid-base reaction between NPX and MEG during melt extrusion significantly improved the physical stability and the dissolution rate of NPX ASDs.

  2. A controlled study of concurrent therapy with a nonacetylated salicylate and naproxen in rheumatoid arthritis.

    PubMed

    Furst, D E; Blocka, K; Cassell, S; Harris, E R; Hirschberg, J M; Josephson, N; Lachenbruch, P A; Trimble, R B; Paulus, H E

    1987-02-01

    Previous studies of combinations of nonsteroidal drugs used in the treatment of rheumatoid arthritis (RA) have yielded conflicting results. We used standard methods to measure disease activity and high pressure liquid chromatography to measure plasma drug concentrations. We used doses of choline magnesium trisalicylate, adjusted to achieve therapeutic serum salicylate concentrations, and naproxen in a randomized, double-blind, placebo-controlled cross-over study of full dose trisalicylate (CMT), full dose naproxen (N), full dose of both (CMT-N), and half dose of both (cmt-n) to examine their relative efficacy and toxicity in treating RA. CMT-N was statistically superior to all other treatments in only 1 of 12 efficacy variables, but was equal to N and better than CMT or cmt-n for 7 variables. There were minimal differences among treatments for the other 4 efficacy variables. The mean percentage difference for the efficacy variables between CMT-N and N was 3%, between CMT-N and CMT was 10.6%, and between CMT-N and cmt-n was 10.5%. Thirteen percent of patients manifested toxic reactions during the initial open dose-adjustment salicylate run-in phase. During the double-blind phases of the study, CMT-N was more toxic than N, CMT, or cmt-n (7.5% versus 3.4%, 1.8%, and 3.7%, respectively). Tinnitus was more common when full-dose CMT was used; N (N or CMT-N) was associated with increased skin toxicity. Gastrointestinal complaints were equally common with all regimens. CMT-N, although sometimes statistically superior to CMT, N, or cmt-n, showed no clinically important additive or synergistic effect versus N or CMT alone.

  3. Rebamipide does not protect against naproxen-induced gastric damage: a randomized double-blind controlled trial.

    PubMed

    Gagliano-Jucá, Thiago; Moreno, Ronilson A; Zaminelli, Tiago; Napolitano, Mauro; Magalhães, Antônio Frederico N; Carvalhaes, Aloísio; Trevisan, Miriam S; Wallace, John L; De Nucci, Gilberto

    2016-06-04

    Rebamipide is a gastroprotective agent with promising results against gastric damage induced by non-steroidal anti-inflammatory drugs. The present study evaluated if rebamipide protects against naproxen-induced gastric damage in healthy volunteers. Changes in gastric PGE2 tissue concentration were also evaluated. After a preliminary endoscopy to rule out previous gastric macroscopic damage, twenty-four healthy volunteers of both sexes were divided into 2 groups. One group received sodium naproxen 550 mg b.i.d. plus placebo for 7 days, while the other group received sodium naproxen 550 mg b.i.d. plus rebamipide 100 mg b.i.d. At the end of treatment, a new endoscopy was performed. Gastric macroscopic damage was evaluated by the Cryer score and by the modified Lanza score. The primary outcome measure of the trial was the macroscopic damage observed in each treatment group at the end of treatment. Biopsies were collected at both endoscopies for PGE2 quantification and histopathological analysis (secondary outcomes). Tissue PGE2 was quantified by ELISA. The randomization sequence was generated using 3 blocks of 8 subjects each. Volunteers and endoscopists were blind to whether they were receiving rebamipide or placebo. All recruited volunteers completed the trial. Sodium naproxen induced gastric damage in both groups. At the end of the study, median Cryer score was 4 in both groups (Difference = 0; 95%CI = -1 to 0; p = 0.728). In the placebo group, the mean tissue PGE2 concentration was 1005 ± 129 pg/mL before treatment and 241 ± 41 pg/mL after treatment (p < 0.001). In the rebamipide group, the mean tissue PGE2 concentration was 999 ± 109 pg/mL before treatment, and 168 ± 13 pg/mL after treatment (p < 0.001). There was no difference in mean tissue PGE2 between the two groups (difference = 5; 95%CI from -334.870 to 345.650; p = 0.975). No significant change was observed at the histopathological evaluation, despite

  4. Efficacy and safety of flavocoxid, a novel therapeutic, compared with naproxen: a randomized multicenter controlled trial in subjects with osteoarthritis of the knee.

    PubMed

    Levy, Robert M; Khokhlov, Alexander; Kopenkin, Sergey; Bart, Boris; Ermolova, Tatiana; Kantemirova, Raiasa; Mazurov, Vadim; Bell, Marjorie; Caldron, Paul; Pillai, Lakshmi; Burnett, Bruce P

    2010-10-01

    Flavocoxid is a novel flavonoid-based "dual inhibitor" of the 5-lipoxygenase (5-LOX) enzyme and the cyclooxygenase (COX) enzymes. This study was designed to compare the effectiveness and safety of flavocoxid to naproxen in subjects with moderate to severe osteoarthritis (OA) of the knee. In this randomized, multicenter, double-blind study, 220 subjects were assigned to receive either flavocoxid (500 mg twice daily) or naproxen (500 mg twice daily) for 12 weeks. The trial was structured to show noninferiority of flavocoxid to naproxen. Primary outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subscales and a timed walk. More than 90% of the subjects in both groups noted significant reduction in the signs and symptoms of knee OA. There were no statistically significant differences in efficacy between the flavocoxid and naproxen groups when the entire intent-to-treat population was analyzed. The flavocoxid group had significantly fewer upper gastrointestinal (UGI) and renal (edema) adverse events (AEs) as well as a strong trend toward fewer respiratory AEs. Flavocoxid, a first-in-class flavonoid-based therapeutic that inhibits COX-1 and COX-2 as well as 5-LOX, was as effective as naproxen in managing the signs and symptoms of OA of the knee. Flavocoxid demonstrated better UGI, renal (edema), and respiratory safety profiles than naproxen.

  5. Improvement of the surface hydrophilic properties of naproxen particles with addition of hydroxypropylmethyl cellulose and sodium dodecyl sulphate: In vitro and in vivo studies.

    PubMed

    García-Herrero, Víctor; Torrado, Carlos; García-Rodríguez, Juan José; López-Sánchez, Alicia; Torrado, Susana; Torrado-Santiago, Santiago

    2017-08-30

    In this study, a new surface-modified naproxen was developed to enhance brain concentration in acute migraine treatment. Fast-dissolving naproxen granules were made by mixing hydroxypropylmethylcellulose (HPMC) sodium dodecyl sulphate (SDS) and sodium croscarmellose with micronized naproxen particles. The aim of this study was to evaluate the effect of adding proportions of SDS to the HPMC film caused changes in the polymer chains of the HPMC, producing a new hydrophilic HPMC-SDS structure. These formulations with different HPMC/SDS ratios were characterised using electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). SDS 10% (w/w) produced a highly hydrophilic HPMC-SDS structure on the surface of the naproxen microparticles. The fast dissolution granules (SF-10%) showed a significant improvement in the dissolution rate of naproxen. Pharmacokinetic studies were conducted with mice, showing an improvement of Cmax (1.38 and 1.41-fold) and AUC0-2h (30% and 10% higher) for plasma and brain samples compared to the reference naproxen suspension. The faster Tmax ratio for SF-10% may be related to increased hydration in the gastrointestinal environment, enabling the drug to permeate the gastrointestinal hydration layer more easily due to the presence of the hydrophilic HPMC-SDS structure in the formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. La fibrose rétropéritonéale: à propos de 12 cas

    PubMed Central

    Majdoub, Aziz El; Khallouk, Abdelhak; Farih, Moulay Hassan

    2017-01-01

    La fibrose rétropéritonéale (FRP) est une maladie rare. Elle se caractérise par la transformation progressive du tissu adipeux rétopéritonéal en une masse fibreuse qui enserre l'aorte, la veine cave inférieure et les voies urinaires responsable d'une altération progressive de la fonction rénale. Le mode habituel de présentation de cette maladie comporte l'association de douleurs lombaires, d'une insuffisance rénale, et d'un syndrome inflammatoire biologique. Nous rapportons 12 cas de fibrose rétropéritonéale dont nous précisons les particularités cliniques, radiologiques et thérapeutiques. Il s'agit d'une étude rétrospective portant sur douze cas de fibrose rétropéritonéale colligés au service d'urologie au CHU Hassan II de Fès durant une période de 9 ans (2005-2013). Il s'agissait de dix hommes et deux femmes. La symptomatologie clinique était très variable, dominée par la douleur lombaire qui était présente chez tous les malades et une hydrocèle chez un patient. Les explorations biologiques avaient montré une insuffisance rénale chez tous les malades et un syndrome inflammatoire chez dix patients. Le diagnostic de la maladie était suspecté dans tous les cas sur les données de l'échographie qui a montré une obstruction de la voie excrétrice supérieure sans obstacle visible chez tous les malades, et confirmé par la TDM abdominale sans injection du produit de contraste qui objectivait une lésion tissulaire rétropéritonéale engainant les vaisseaux et les voies urinaires. Dans notre série, la fibrose rétropéritonéale était idiopathique dans neuf cas. Elle était péri anévrysmale chez deux malades, et post radiothérapie chez un malade. Tous nos patients avaient bénéficié d'un drainage urinaire par sonde urétérale double J. Sept malades avaient reçu une corticothérapie. Une amélioration clinique et biologique, avec disparition de la douleur et amélioration de l'état général, a été observée chez 6

  7. Do you see what I see? Optical morphology and visual capability of ‘disco’ clams (Ctenoides ales)

    PubMed Central

    Dubielzig, Richard R.; Schobert, Charles S.; Teixeira, Leandro B.; Li, Jingchun

    2017-01-01

    ABSTRACT The ‘disco’ clam Ctenoides ales (Finlay, 1927) is a marine bivalve that has a unique, vivid flashing display that is a result of light scattering by silica nanospheres and rapid mantle movement. The eyes of C. ales were examined to determine their visual capabilities and whether the clams can see the flashing of conspecifics. Similar to the congener C. scaber, C. ales exhibits an off-response (shadow reflex) and an on-response (light reflex). In field observations, a shadow caused a significant increase in flash rate from a mean of 3.9 Hz to 4.7 Hz (P=0.0016). In laboratory trials, a looming stimulus, which increased light intensity, caused a significant increase in flash rate from a median of 1.8 Hz to 2.2 Hz (P=0.0001). Morphological analysis of the eyes of C. ales revealed coarsely-packed photoreceptors lacking sophisticated structure, resulting in visual resolution that is likely too low to detect the flashing of conspecifics. As the eyes of C. ales are incapable of perceiving conspecific flashing, it is likely that their vision is instead used to detect predators. PMID:28396488

  8. Modeling The Shock Initiation of PBX-9501 in ALE3D

    SciTech Connect

    Leininger, L; Springer, H K; Mace, J

    The SMIS (Specific Munitions Impact Scenario) experimental series performed at Los Alamos National Laboratory has determined the 3-dimensional shock initiation behavior of the HMX-based heterogeneous high explosive, PBX 9501. A series of finite element impact calculations have been performed in the ALE3D [1] hydrodynamic code and compared to the SMIS results to validate the code predictions. The SMIS tests use a powder gun to shoot scaled NATO standard fragments at a cylinder of PBX 9501, which has a PMMA case and a steel impact cover. The SMIS real-world shot scenario creates a unique test-bed because many of the fragments arrivemore » at the impact plate off-center and at an angle of impact. The goal of this model validation experiments is to demonstrate the predictive capability of the Tarver-Lee Ignition and Growth (I&G) reactive flow model [2] in this fully 3-dimensional regime of Shock to Detonation Transition (SDT). The 3-dimensional Arbitrary Lagrange Eulerian hydrodynamic model in ALE3D applies the Ignition and Growth (I&G) reactive flow model with PBX 9501 parameters derived from historical 1-dimensional experimental data. The model includes the off-center and angle of impact variations seen in the experiments. Qualitatively, the ALE3D I&G calculations accurately reproduce the 'Go/No-Go' threshold of the Shock to Detonation Transition (SDT) reaction in the explosive, as well as the case expansion recorded by a high-speed optical camera. Quantitatively, the calculations show good agreement with the shock time of arrival at internal and external diagnostic pins. This exercise demonstrates the utility of the Ignition and Growth model applied in a predictive fashion for the response of heterogeneous high explosives in the SDT regime.« less

  9. Reactive Flow Modeling of Liquid Explosives via ALE3D/Cheetah Simulations

    SciTech Connect

    Kuo, I W; Bastea, S; Fried, L E

    2010-03-10

    We carried out reactive flow simulations of liquid explosives such as nitromethane using the hydrodynamic code ALE3D coupled with equations of state and reaction kinetics modeled by the thermochemical code Cheetah. The simulation set-up was chosen to mimic cylinder experiments. For pure unconfined nitromethane we find that the failure diameter and detonation velocity dependence on charge diameter are in agreement with available experimental results. Such simulations are likely to be useful for determining detonability and failure behavior for a wide range of experimental conditions and explosive compounds.

  10. An asymptotic preserving multidimensional ALE method for a system of two compressible flows coupled with friction

    NASA Astrophysics Data System (ADS)

    Del Pino, S.; Labourasse, E.; Morel, G.

    2018-06-01

    We present a multidimensional asymptotic preserving scheme for the approximation of a mixture of compressible flows. Fluids are modelled by two Euler systems of equations coupled with a friction term. The asymptotic preserving property is mandatory for this kind of model, to derive a scheme that behaves well in all regimes (i.e. whatever the friction parameter value is). The method we propose is defined in ALE coordinates, using a Lagrange plus remap approach. This imposes a multidimensional definition and analysis of the scheme.

  11. The ALE Discontinuous Galerkin Method for the Simulatio of Air Flow Through Pulsating Human Vocal Folds

    NASA Astrophysics Data System (ADS)

    Feistauer, Miloslav; Kučera, Václav; Prokopová, Jaroslav; Horáček, Jaromír

    2010-09-01

    The aim of this work is the simulation of viscous compressible flows in human vocal folds during phonation. The computational domain is a bounded subset of IR2, whose geometry mimics the shape of the human larynx. During phonation, parts of the solid impermeable walls are moving in a prescribed manner, thus simulating the opening and closing of the vocal chords. As the governing equations we take the compressible Navier-Stokes equations in ALE form. Space semidiscretization is carried out by the discontinuous Galerkin method combined with a linearized semi-implicit approach. Numerical experiments are performed with the resulting scheme.

  12. Forced folding in a salty basin: Gada'-Ale in the Afar

    NASA Astrophysics Data System (ADS)

    Rafflin, Victoria; Hetherington, Rachel; Hagos, Miruts; van Wyk de Vries, Benjamin

    2017-04-01

    The Gada'-Ale Volcano in the Danakil Depression of Ethiopia is a curious shield-like, or flat dome-like volcanic centre in the Afar Rift. It has several fissure eruptions seen on its mid and lower flanks. It has an even more curious ring structure on its western side that has been interpreted as a salt diapir. The complex lies the central part of the basin where there are 1-2 km thick salt deposits. The area was active in 1990's (Amelung et al 2000) with no eruptive activity, but a possible intrusion. There was also an intrusion north of Gada'-Ale at Dallol in 2005 (Nobile et al 2012). Using Google Earth imagery, we have mapped the volcano, and note that: a) the main edifice has a thin skin of lava lying light coloured rock; b) that these thin deposits are sliding down the flank of volcano, and thrusting at the base. In doing so, they are breaking into detached plates. The light colour of the deposits, and the ability of the rock to slide on them suggest that are salt; Fractures on and around the volcano form curved patterns, around raised areas with several km diameter. These could be surface expressions of shallow sills. Putting the observations together with the known geology of adjacent centres like Dallol and Alu, we suggest that Gada'-Ale is a forced fold, created over a sill that has either bulged into a laccolith, or risen as a saucer-shaped sill. The upraised salt has caused the thin veneer of volcanics to slide off. That there are eruptive fissures on Gada'-Ale, and possible sill intrusions around the base suggests that the centre lies over a complex of sills that have gradually intruded and bulged the structure to its present level. Eruptions have contribute only a small amount to the whole topography of the edifice. We hope to visit the volcano in March and will being hot-off-the press details back to the EGU!

  13. Overview of SPH-ALE applications for hydraulic turbines in ANDRITZ Hydro

    NASA Astrophysics Data System (ADS)

    Rentschler, M.; Marongiu, J. C.; Neuhauser, M.; Parkinson, E.

    2018-02-01

    Over the past 13 years, ANDRITZ Hydro has developed an in-house tool based on the SPH-ALE method for applications in flow simulations in hydraulic turbines. The initial motivation is related to the challenging simulation of free surface flows in Pelton turbines, where highly dynamic water jets interact with rotating buckets, creating thin water jets traveling inside the housing and possibly causing disturbances on the runner. The present paper proposes an overview of industrial applications allowed by the developed tool, including design evaluation of Pelton runners and casings, transient operation of Pelton units and free surface flows in hydraulic structures.

  14. Brief Report: Course of Active Inflammatory and Fatty Lesions in Patients With Early Axial Spondyloarthritis Treated With Infliximab Plus Naproxen as Compared to Naproxen Alone: Results From the Infliximab As First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial.

    PubMed

    Poddubnyy, Denis; Listing, Joachim; Sieper, Joachim

    2016-08-01

    To investigate the course of active inflammatory and fatty lesions seen on magnetic resonance imaging (MRI) in patients with early axial spondyloarthritis (SpA) treated with the tumor necrosis factor (TNF) inhibitor infliximab added to naproxen as compared to those treated with naproxen alone. A total of 158 patients with active axial SpA were randomized (2:1) to receive 28 weeks of treatment with either infliximab 5 mg/kg plus naproxen 1,000 mg/day or placebo plus naproxen 1,000 mg/day. MRI of the sacroiliac (SI) joints and of the spine was performed at baseline and week 28. Images were scored for active inflammation and for fatty lesions. After 28 weeks, there was a significant reduction of inflammation in the spine and in the SI joints in both treatment groups, which was, however, more prominent in the infliximab plus naproxen group (mean ± SD spine osteitis change score -2.9 ± 5.1, versus -2.0 ± 4.2 in the placebo plus naproxen group [P < 0.001]; SI joint osteitis change score -4.3 ± 5.2 in the infliximab plus naproxen group versus -3.9 ± 3.7 in the placebo plus naproxen group [P = 0.003]). Similarly, there was a significant increase in the fatty lesion score after 28 weeks in both groups; this change did not, however, differ significantly between groups (spine fatty lesion change score 0.8 ± 1.7 in the infliximab plus naproxen group versus 1.0 ± 1.8 in the placebo plus naproxen group [P = 0.72]; SI joint fatty lesion change score 1.7 ± 2.7 in the infliximab plus naproxen group versus 1.4 ± 2.6 in the placebo plus naproxen group [P = 0.86]). These findings indicate that effective antiinflammatory treatment of axial SpA is associated with an increase in fatty lesion scores, independent of concomitant treatment with or without anti-TNF. © 2016, American College of Rheumatology.

  15. Sorption of diclofenac and naproxen onto MWCNT in model wastewater treated by H2O2 and/or UV.

    PubMed

    Czech, Bożena; Oleszczuk, Patryk

    2016-04-01

    The application of oxidation processes such as UV and/or H2O2 will change the physicochemical properties of carbon nanotubes (CNT). It may affect the sorption affinity of CNT to different contaminants and then affect their fate in the environment. In the present study the adsorption of two very common used pharmaceuticals (diclofenac and naproxen) onto CNT treated by UV, H2O2 or UV/H2O2 was investigated. Four different adsorption models (Freundlich, Langmuir, Temkin, Dubinin-Radushkevich) were tested. The best fitting of experimental data was observed for Freundlich or Langmuir model. The significant relationships between Q calculated from Langmuir model with O% and dispersity were observed. Kinetics of diclofenac and naproxen followed mainly pseudo-second order indicating for chemisorption limiting step of adsorption. The data showed that the mechanism of sorption was physical or chemical depending on the type of CNT modification. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Efficacy and safety of flavocoxid compared with naproxen in subjects with osteoarthritis of the knee- a subset analysis.

    PubMed

    Levy, Robert; Khokhlov, Alexander; Kopenkin, Sergey; Bart, Boris; Ermolova, Tatiana; Kantemirova, Raiasa; Mazurov, Vadim; Bell, Marjorie; Caldron, Paul; Pillai, Lakshmi; Burnett, Bruce

    2010-12-01

    twice-daily flavocoxid, a cyclooxygenase and 5-lipoxygenase inhibitor with potent antioxidant activity of botanical origin, was evaluated for 12 weeks in a randomized, double-blind, active-comparator study against naproxen in 220 subjects with moderate-severe osteoarthritis (OA) of the knee. As previously reported, both groups noted a significant reduction in the signs and symptoms of OA with no detectable differences in efficacy between the groups when the entire intent-to-treat population was considered. This post-hoc analysis compares the efficacy of flavocoxid to naproxen in different subsets of patients, specifically those related to age, gender, and disease severity as reported at baseline for individual response parameters. in the original randomized, double-blind study, 220 subjects were assigned to receive either flavocoxid (500 mg twice daily) or naproxen (500 mg twice daily) for 12 weeks. In this subgroup analysis, primary outcome measures including the Western Ontario and McMaster Universities OA index and subscales, timed walk, and secondary efficacy variables, including investigator global assessment for disease and global response to treatment, subject visual analog scale for discomfort, overall disease activity, global response to treatment, index joint tenderness and mobility, were evaluated for differing trends between the study groups. subset analyses revealed some statistically significant differences and some notable trends in favor of the flavocoxid group. These trends became stronger the longer the subjects continued on therapy. These observations were specifically noted in older subjects (>60 years), males and in subjects with milder disease, particularly those with lower subject global assessment of disease activity and investigator global assessment for disease and faster walking times at baseline. initial analysis of the entire intent-to-treat population revealed that flavocoxid was as effective as naproxen in managing the signs and

  17. Model-based analysis of thromboxane B₂ and prostaglandin E₂ as biomarkers in the safety evaluation of naproxen.

    PubMed

    Sahota, Tarjinder; Sanderson, Ian; Danhof, Meindert; Della Pasqua, Oscar

    2014-08-01

    The assessment of safety in traditional toxicology protocols relies on evidence arising from observed adverse events (AEs) in animals and on establishing their correlation with different measures of drug exposure (e.g., Cmax and AUC). Such correlations, however, ignore the role of biomarkers, which can provide further insight into the underlying pharmacological mechanisms. Here we use naproxen as a paradigm drug to explore the feasibility of a biomarker-guided approach for the prediction of AEs in humans. A standard toxicology protocol was set up for the evaluation of effects of naproxen in rat, in which four doses were tested (7.5, 15, 40 and 80 mg/kg). In addition to sparse blood sampling for the assessment of exposure, thromboxane B₂ and prostaglandin E₂ were also collected in satellite groups. Nonlinear mixed effects modelling was used to evaluate the predictive performance of the approach. A one-compartmental model with first order absorption was found to best describe the pharmacokinetics of naproxen. A nonlinear relationship between dose and bioavailability was observed which leads to a less than proportional increase in naproxen concentrations with increasing doses. The pharmacodynamics of TXB₂ and PGE₂ was described by direct inhibition models with maximum pharmacological effects achieved at doses >7.5 mg/kg. The predicted PKPD relationship in humans was within 10-fold of the values previously published. Moreover, our results indicate that biomarkers can be used to assess interspecies differences in PKPD and extrapolated data from animals to humans. Biomarker sampling should be used systematically in general toxicity studies. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Selective inhibition by aspirin and naproxen of mainstream cigarette smoke-induced genotoxicity and lung tumors in female mice.

    PubMed

    Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Micale, Rosanna T; La Maestra, Sebastiano; D'Oria, Chiara; Steele, Vernon E; De Flora, Silvio

    2016-05-01

    The role of nonsteroidal anti-inflammatory drugs (NSAIDs) in smoke-related lung carcinogenesis is still controversial. We have developed and validated a murine model for evaluating the tumorigenicity of mainstream cigarette smoke (MCS) and its modulation by chemopreventive agents. In the present study, the protective effects of the nonselective cyclooxygenase inhibitors aspirin and naproxen were investigated by using a total of 277 Swiss H neonatal mice of both genders. Groups of mice were exposed whole-body to MCS during the first 4 months of life, followed by an additional 3.5 months in filtered air in order to allow a better growth of tumors. Aspirin (1600 mg/kg diet) and naproxen (320 mg/kg diet) were given after weanling until the end of the experiment. After 4 months of exposure, MCS significantly enhanced the frequency of micronucleated normochromatic erythrocytes in the peripheral blood of mice, and naproxen prevented such systemic genotoxic damage in female mice. After 7.5 months, exposure of mice to MCS resulted in the formation of lung tumors, both benign and malignant, and in several other histopathological lesions detectable both in the respiratory tract and in the urinary tract. Aspirin and, even more sharply, naproxen significantly inhibited the formation of lung tumors in MCS-exposed mice, but this protective effect selectively occurred in female mice only. These results lend support to the views that estrogens are involved in smoke-related pulmonary carcinogenesis and that NSAIDs have antiestrogenic properties. The two NSAIDs proved to be safe and efficacious in the experimental model used.

  19. Influence of the cooling rate and the blend ratio on the physical stability of co-amorphous naproxen/indomethacin.

    PubMed

    Beyer, Andreas; Grohganz, Holger; Löbmann, Korbinian; Rades, Thomas; Leopold, Claudia S

    2016-12-01

    Co-amorphization represents a promising approach to increase the physical stability and dissolution rate of amorphous active pharmaceutical ingredients (APIs) as an alternative to polymer glass solutions. For amorphous and co-amorphous systems, it is reported that the preparation method and the blend ratio play major roles with regard to the resulting physical stability. Therefore, in the present study, co-amorphous naproxen-indomethacin (NAP/IND) was prepared by melt-quenching at three different cooling rates and at ten different NAP/IND blend ratios. The samples were analyzed using XRPD and FTIR, both directly after preparation and during storage to investigate their physical stabilities. All cooling methods led to fully amorphous samples, but with significantly different physical stabilities. Samples prepared by fast cooling had a higher degree of crystallinity after 300d of storage than samples prepared by intermediate cooling and slow cooling. Intermediate cooling was subsequently used to prepare co-amorphous NAP/IND at different blend ratios. In a previous study, it was postulated that the equimolar (0.5:0.5) co-amorphous blend of NAP/IND is most stable. However, in the present study the physically most stable blend was found for a NAP/IND ratio of 0.6:0.4, which also represents the eutectic composition of the crystalline NAP/γ-IND system. This indicates that the eutectic point may be of major importance for the stability of binary co-amorphous systems. Slight deviations from the optimal naproxen molar fraction led to significant recrystallization during storage. Either naproxen or γ-indomethacin recrystallized until a naproxen molar fraction of about 0.6 in the residual co-amorphous phase was reached again. In conclusion, the physical stability of co-amorphous NAP/IND may be significantly improved, if suitable preparation conditions and the optimal phase composition are chosen. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Relief of Menstrual Symptoms and Migraine with a Single-Tablet Formulation of Sumatriptan and Naproxen Sodium

    PubMed Central

    Ballard, Jeanne; Diamond, Michael P.; Mannix, Lisa K.; Derosier, Frederick J.; Lener, Shelly E.; Krishen, Alok; McDonald, Susan A.

    2014-01-01

    Abstract Background: Dysmenorrhea and menstrual migraine may share a common pathogenic pathway. Both appear to be mediated, in part, by an excess of prostaglandin production that occurs during menstruation. Methods: Data were pooled from two replicate randomized controlled trials of 621 adult menstrual migraineurs with dysmenorrhea who treated migraine with sumatriptan-naproxen or placebo. Along with headache symptoms, nonpain menstrual symptoms (bloating, fatigue, and irritability) and menstrual pain symptoms (abdominal and back pain) were recorded at the time periods of 30 minutes and 1, 2, 4, and 4–24 hours. Relief of menstrual symptoms was compared using a Cochran-Mantel-Haenszel test. Logistic regression was used to determine the odds of a headache response with increasing numbers of moderate to severe dymenorrheic symptoms. Results: Sumatriptan-naproxen was superior to placebo for relief of tiredness, irritability, and abdominal pain at the time periods of 2, 4, and 4–24 hours (p≤0.023); back pain at the time periods of 4 and 4–24 hours (p≤0.023); and bloating at 4–24 hours endpoint (p=0.01). The odds ratios (ORs) of attaining migraine pain freedom for 2 hours and for sustained 2–24 hours decreased as moderate to severe dysmenorrhea symptoms increased with sumatriptan-naproxen versus placebo. Conclusions: Treatment with sumatriptan-naproxen may provide relief of menstrual symptoms and migraine in female migraineurs with dysmenorrhea. The presence of moderate to severe dysmenorrhea symptoms is associated with decreased response rates for menstrual migraine, suggesting that the co-occurrence of these disorders may negatively impact the results of migraine-abortive therapy. PMID:24579886

  1. Melt extrusion vs. spray drying: The effect of processing methods on crystalline content of naproxen-povidone formulations.

    PubMed

    Haser, Abbe; Cao, Tu; Lubach, Joe; Listro, Tony; Acquarulo, Larry; Zhang, Feng

    2017-05-01

    Our hypothesis is that melt extrusion is a more suitable processing method than spray drying to prepare amorphous solid dispersions of drugs with a high crystallization tendency. Naproxen-povidone K25 was used as the model system in this study. Naproxen-povidone K25 solid dispersions at 30% and 60% drug loadings were characterized by modulated DSC, powder X-ray diffraction, FT-IR, and solid-state 13 C NMR to identify phase separation and drug recrystallization during processing and storage. At 30% drug loading, hydrogen bond (H-bond) sites of povidone K25 were not saturated and the glass transition (T g ) temperature of the formulation was higher. As a result, both melt-extruded and spray-dried materials were amorphous initially and remained so after storage at 40°C. At 60% drug loading, H-bond sites were saturated, and T g was low. We were not able to prepare amorphous materials. The initial crystallinity of the formulations was 0.4%±0.2% and 5.6%±0.6%, and increased to 2.7%±0.3% and 21.6%±1.0% for melt-extruded and spray-dried materials, respectively. Spray-dried material was more susceptible to re-crystallization during processing, due to the high diffusivity of naproxen molecules in the formulation matrix and lack of kinetic stabilization from polymer solution. A larger number of crystalline nucleation sites and high surface area made the spray-dried material more susceptible to recrystallization during storage. This study demonstrated the unique advantages of melt extrusion over spray drying for the preparation of amorphous solid dispersions of naproxen at high drug level. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Atmospheric emissions and trends of nitrous oxide deduced from 10 years of ALE-GAGE data

    NASA Technical Reports Server (NTRS)

    Prinn, R.; Cunnold, D.; Alyea, F.; Rasmussen, R.; Simmonds, P.

    1990-01-01

    Long-term measurements of nitrous oxide (N2O) obtained during the Atmospheric Lifetime Experiment (ALE) and the Global Atmospheric Gases Experiment (GAGE) for a period from 1978 to 1988 are presented and interpreted. It is observed that the average concentration in the Northern Hemisphere is 0.75 +/- 0.16 ppbv higher than in the Southern Hemisphere and that the global average linear trend in N2O lies in the range from 0.25 to 0.31 percent/year. The measured trends and latitudinal distributions are shown to be consistent with the hypothesis that stratospheric photodissociation is the major atmospheric sink for N2O, while the cause of the N2O trend is suggested to be a combination of a growing tropical source and a growing Northern mid-latitude source. A 10-year average global N2O emission rate of (20.5 +/- 2.4) x 10 to the 12th g N2O/year is deduced from the ALE/GAGE data.

  3. The Atmospheric Lifetime Experiment and the Global Atmospheric Gas Experiment (ALE/GAGE)

    NASA Technical Reports Server (NTRS)

    Rasmussen, R. A.; Khalil, M. Aslam K.

    1995-01-01

    The ALE/GAGE project was designed to determine the global atmospheric lifetimes of the chlorofluorocarbons CCl3F and CCl2F2 (F-11 and F-12), which had been identified as the main gases that cause stratospheric ozone depletion. The experimental procedures also provided the concentrations of CH3CCl3, CCl4 and N2O. The extended role of the project was to evaluate the mass balances of these gases as well. Methylchloroform (CH3CCl3) serves as a tracer of average atmospheric OH concentrations and hence the oxidizing capacity of the atmosphere. Nitrous oxide (N2O) is a potent greenhouse gas and can also deplete the ozone layer. Measurements of these gases were taken with optimized instruments in the field at a frequency of about 1 sample/hr. Toward the end of the present project methane measurements were added to the program. The final report deals with the research of the Oregon Graduate Institute (OGI) as part of the ALE/GAGE program between 4/1/1988 and 1/31/1991. The report defines the scope of the OGI project, the approach, and the results.

  4. Voxel-Based Morphometry ALE meta-analysis of Bipolar Disorder

    NASA Astrophysics Data System (ADS)

    Magana, Omar; Laird, Robert

    2012-03-01

    A meta-analysis was performed independently to view the changes in gray matter (GM) on patients with Bipolar disorder (BP). The meta-analysis was conducted on a Talairach Space using GingerALE to determine the voxels and their permutation. In order to achieve the data acquisition, published experiments and similar research studies were uploaded onto the online Voxel-Based Morphometry database (VBM). By doing so, coordinates of activation locations were extracted from Bipolar disorder related journals utilizing Sleuth. Once the coordinates of given experiments were selected and imported to GingerALE, a Gaussian was performed on all foci points to create the concentration points of GM on BP patients. The results included volume reductions and variations of GM between Normal Healthy controls and Patients with Bipolar disorder. A significant amount of GM clusters were obtained in Normal Healthy controls over BP patients on the right precentral gyrus, right anterior cingulate, and the left inferior frontal gyrus. In future research, more published journals could be uploaded onto the database and another VBM meta-analysis could be performed including more activation coordinates or a variation of age groups.

  5. ALE Meta-Analysis of Schizophrenics Performing the N-Back Task

    NASA Astrophysics Data System (ADS)

    Harrell, Zachary

    2010-10-01

    MRI/fMRI has already proven itself as a valuable tool in the diagnosis and treatment of many illnesses of the brain, including cognitive problems. By exploiting the differences in magnetic susceptibility between oxygenated and deoxygenated hemoglobin, fMRI can measure blood flow in various regions of interest within the brain. This can determine the level of brain activity in relation to motor or cognitive functions and provide a metric for tissue damage or illness symptoms. Structural imaging techniques have shown lesions or deficiencies in tissue volumes in schizophrenics corresponding to areas primarily in the frontal and temporal lobes. These areas are currently known to be involved in working memory and attention, which many schizophrenics have trouble with. The ALE (Activation Likelihood Estimation) Meta-Analysis is able to statistically determine the significance of brain area activations based on the post-hoc combination of multiple studies. This process is useful for giving a general model of brain function in relation to a particular task designed to engage the affected areas (such as working memory for the n-back task). The advantages of the ALE Meta-Analysis include elimination of single subject anomalies, elimination of false/extremely weak activations, and verification of function/location hypotheses.

  6. History of the pharmacies in the town of Aleşd, Bihor county

    PubMed Central

    PAŞCA, MANUELA BIANCA; GÎTEA, DANIELA; MOISA, CORINA

    2013-01-01

    In 1848 pharmacist Horváth Mihály established the first pharmacy in Aleşd, called Speranţa (Remény). Following the brief history of this pharmacy we will notice that in 1874 the pharmacy comes into the possession of Kocsiss József. In 1906 the personal rights of the pharmacy are transcribed to Kocsiss Béla, and since 1938 the his son, Kocsiss Dezső, pharmacist, became the new owner. In 1949 the pharmacy was nationalized and became the property of the Pharmaceutical Office Oradea, the pharmacy got the name Farmacia nr. 22 of Aleşd, and continued its activity throughout the whole communist period. Starting with the year 1991 it entered into private system as Angefarm, as the property of Mermeze Gheorghe, pharmacist, and from 2003 until now works under the name Vitalogy 3, as the property of Ghitea Sorin. A second pharmacy, Sfântul Anton was founded in 1937 by pharmacist Herceg Dobreanu Atena, which however had no continuity during the communist period. PMID:26527963

  7. Hypnosis and pain perception: An Activation Likelihood Estimation (ALE) meta-analysis of functional neuroimaging studies.

    PubMed

    Del Casale, Antonio; Ferracuti, Stefano; Rapinesi, Chiara; De Rossi, Pietro; Angeletti, Gloria; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo

    2015-12-01

    Several studies reported that hypnosis can modulate pain perception and tolerance by affecting cortical and subcortical activity in brain regions involved in these processes. We conducted an Activation Likelihood Estimation (ALE) meta-analysis on functional neuroimaging studies of pain perception under hypnosis to identify brain activation-deactivation patterns occurring during hypnotic suggestions aiming at pain reduction, including hypnotic analgesic, pleasant, or depersonalization suggestions (HASs). We searched the PubMed, Embase and PsycInfo databases; we included papers published in peer-reviewed journals dealing with functional neuroimaging and hypnosis-modulated pain perception. The ALE meta-analysis encompassed data from 75 healthy volunteers reported in 8 functional neuroimaging studies. HASs during experimentally-induced pain compared to control conditions correlated with significant activations of the right anterior cingulate cortex (Brodmann's Area [BA] 32), left superior frontal gyrus (BA 6), and right insula, and deactivation of right midline nuclei of the thalamus. HASs during experimental pain impact both cortical and subcortical brain activity. The anterior cingulate, left superior frontal, and right insular cortices activation increases could induce a thalamic deactivation (top-down inhibition), which may correlate with reductions in pain intensity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. ALE3D Simulation and Measurement of Violence in a Fast Cookoff Experiment with LX-10

    SciTech Connect

    McClelland, M A; Maienschein, J L; Howard, W M

    We performed a computational and experimental analysis of fast cookoff of LX-10 (94.7% HMX, 5.3% Viton A) confined in a 2 kbar steel tube with reinforced end caps. A Scaled-Thermal-Explosion-eXperiment (STEX) was completed in which three radiant heaters were used to heat the vessel until ignition, resulting in a moderately violent explosion after 20.4 minutes. Thermocouple measurements showed tube temperatures as high as 340 C at ignition and LX-10 surface temperatures as high as 279 C, which is near the melting point of HMX. Three micro-power radar systems were used to measure mean fragment velocities of 840 m/s. Photonics Dopplermore » Velocimeters (PDVs) showed a rapid acceleration of fragments over 80 {micro}s. A one-dimensional ALE3D cookoff model at the vessel midplane was used to simulate the heating, thermal expansion, LX-10 decomposition composition, and closing of the gap between the HE (High Explosive) and vessel wall. Although the ALE3D simulation terminated before ignition, the model provided a good representation of heat transfer through the case and across the dynamic gap to the explosive.« less

  9. Validation of Air-Backed Underwater Explosion Experiments with ALE3D

    SciTech Connect

    Leininger, L D

    2005-02-04

    This paper summarizes an exercise carried out to validate the process of implementing LLNL's ALE3D to predict the permanent deformation and rupture of an air-backed steel plate subjected to underwater shock. Experiments were performed in a shock tank at the Naval Science and Technology Laboratory in Visakhapatnam India, and the results are documented in reference. A consistent set of air-backed plates is subjected to shocks from increasing weights of explosives ranging from 10g-80g. At 40g and above, rupture is recorded in the experiment and, without fracture mechanics implemented in ALE3D, only the cases of 10g, 20g, and 30g are presentedmore » here. This methodology applies the Jones-Wilkins-Lee (JWL) Equation of State (EOS) to predict the pressure of the expanding detonation products, the Gruneisein EOS for water under highly dynamic compressible flow - both on 1-point integrated 3-d continuum elements. The steel plates apply a bilinear elastic-plastic response with failure and are simulated with 3-point integrated shell elements. The failure for this exercise is based on effective (or equivalent) plastic strain.« less

  10. Multi-Material ALE with AMR for Modeling Hot Plasmas and Cold Fragmenting Materials

    NASA Astrophysics Data System (ADS)

    Alice, Koniges; Nathan, Masters; Aaron, Fisher; David, Eder; Wangyi, Liu; Robert, Anderson; David, Benson; Andrea, Bertozzi

    2015-02-01

    We have developed a new 3D multi-physics multi-material code, ALE-AMR, which combines Arbitrary Lagrangian Eulerian (ALE) hydrodynamics with Adaptive Mesh Refinement (AMR) to connect the continuum to the microstructural regimes. The code is unique in its ability to model hot radiating plasmas and cold fragmenting solids. New numerical techniques were developed for many of the physics packages to work efficiently on a dynamically moving and adapting mesh. We use interface reconstruction based on volume fractions of the material components within mixed zones and reconstruct interfaces as needed. This interface reconstruction model is also used for void coalescence and fragmentation. A flexible strength/failure framework allows for pluggable material models, which may require material history arrays to determine the level of accumulated damage or the evolving yield stress in J2 plasticity models. For some applications laser rays are propagating through a virtual composite mesh consisting of the finest resolution representation of the modeled space. A new 2nd order accurate diffusion solver has been implemented for the thermal conduction and radiation transport packages. One application area is the modeling of laser/target effects including debris/shrapnel generation. Other application areas include warm dense matter, EUV lithography, and material wall interactions for fusion devices.

  11. Validated HPLC-UV method for determination of naproxen in human plasma with proven selectivity against ibuprofen and paracetamol.

    PubMed

    Filist, Monika; Szlaska, Iwona; Kaza, Michał; Pawiński, Tomasz

    2016-06-01

    Estimating the influence of interfering compounds present in the biological matrix on the determination of an analyte is one of the most important tasks during bioanalytical method development and validation. Interferences from endogenous components and, if necessary, from major metabolites as well as possible co-administered medications should be evaluated during a selectivity test. This paper describes a simple, rapid and cost-effective HPLC-UV method for the determination of naproxen in human plasma in the presence of two other analgesics, ibuprofen and paracetamol. Sample preparation is based on a simple liquid-liquid extraction procedure with a short, 5 s mixing time. Fenoprofen, which is characterized by a similar structure and properties to naproxen, was first used as the internal standard. The calibration curve is linear in the concentration range of 0.5-80.0 µg/mL, which is suitable for pharmacokinetic studies following a single 220 mg oral dose of naproxen sodium. The method was fully validated according to international guidelines and was successfully applied in a bioequivalence study in humans. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Environmental fate of naproxen, carbamazepine and triclosan in wastewater, surface water and wastewater irrigated soil - Results of laboratory scale experiments.

    PubMed

    Durán-Álvarez, J C; Prado, B; González, D; Sánchez, Y; Jiménez-Cisneros, B

    2015-12-15

    Lab-scale photolysis, biodegradation and transport experiments were carried out for naproxen, carbamazepine and triclosan in soil, wastewater and surface water from a region where untreated wastewater is used for agricultural irrigation. Results showed that both photolysis and biodegradation occurred for the three emerging pollutants in the tested matrices as follows: triclosan>naproxen>carbamazepine. The highest photolysis rate for the three pollutants was obtained in experiments using surface water, while biodegradation rates were higher in wastewater and soil than in surface water. Carbamazepine showed to be recalcitrant to biodegradation both in soil and water; although photolysis occurred at a higher level than biodegradation, this compound was poorly degraded by natural processes. Transport experiments showed that naproxen was the most mobile compound through the first 30cm of the soil profile; conversely, the mobility of carbamazepine and triclosan through the soil was delayed. Biodegradation of target pollutants occurred within soil columns during transport experiments. Triclosan was not detected either in leachates or the soil in columns, suggesting its complete biodegradation. Data of these experiments can be used to develop more reliable fate-on-the-field and environmental risk assessment studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Comparison of the effect of naproxen, etodolac and diclofenac on postoperative sequels following third molar surgery: A randomised, double-blind, crossover study

    PubMed Central

    Akbulut, Nihat; Atakan, Cemal; Çölok, Gülümser

    2014-01-01

    Objectives: To compare the three non-steroidal anti-inflammatory agents (NSAIDs) diclofenac potassium, etodolac and naproxen sodium in relation to pain, swelling and trismus following impacted third molar surgery. Study Design: The study was a randomized and a double-blinded study which included 42 healthy young individuals with impacted third molars and bone retention. Patients were randomly assigned to 3 groups (n: 14) to which diclofenac potassium, naproxen sodium and etodolac were administered orally an hour before the operation. Impacted third molars were surgically extracted with local anaesthesia. Visual analog scales (VAS) were used to assess the pain in the 6th, 12th hours and on the 1st, 2nd, 3rd, 5th, and 7th days postoperatively. Swelling was evaluated using ultrasound (US) and mouth opening (trismus) was measured with a composing stick pre and post operatively on the 2nd and 7th days respectively. Results: Regarding pain alleviation, diclofenac potassium was better than naproxen sodium and naproxen sodium was better than etodolac but these differences were not statistically significant. US measurements showed that the swelling on postoperative 2nd day was significantly lowest with diclofenac potassium as compared to others (p= 0.027) while naproxen sodium and etodolac acted similarly (p=0.747). No difference was noted regarding trismus in any of the groups. Conclusions: NSAIDs (diclofenac, naproxen and etodolac) are somehow similarly effective for controlling pain and trismus following extraction of mandibular third molars but diclofenac potassium surpasses others in reduction of swelling. Key words:Diclofenac potassium, naproxen sodium, etodolac, impacted third molar surgery, pain, swelling, trismus. PMID:24316711

  14. Simultaneous quantification of naproxcinod and its active metabolite naproxen in rat plasma using LC-MS/MS: application to a pharmacokinetic study.

    PubMed

    Shi, Xiaowei; Shang, Weiding; Wang, Shuang; Xue, Na; Hao, Yanxia; Wang, Yabo; Sun, Mengmeng; Du, Yumin; Cao, Deying; Zhang, Kai; Shi, Qingwen

    2015-01-26

    In this study, a liquid chromatography-tandem mass spectrometry method was developed and validated to simultaneously determine naproxcinod and naproxen concentrations in rat plasma for the first time. Plasma samples were prepared by simple one-step extraction with methanol for protein precipitation using only 50 μL plasma. Separation was performed on a Synergi Fusion-RP C18 column with a run time of 4 min. Naproxcinod, naproxen and internal standard concentrations were detected in the positive ion mode using multiple reaction monitoring (MRM) of the transitions at m/z 348.2→302.2, 231.1→185.1 and 271.2→203.1, respectively. The calibration curves were linear, with all correlation coefficients being ≥0.9952, in the range of 1.00-400 ng/mL for naproxcinod and 20.0-8000 ng/mL for naproxen. Their accuracy was in the range of -8.1% to 8.7%, and the intra- and inter-day variations were ≤4.53%. The mean extraction recovery of all analytes was more than 93.1% efficient. Stability testing showed that naproxcinod and naproxen remained stable during the whole analytical procedure. After validation, the method was successfully applied to a pharmacokinetic study of naproxcinod and naproxen in rats. The AUC0-∞ of naproxen was 74.6 times larger than that of naproxcinod, which indicated that naproxcinod was rapidly metabolized into naproxen in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Diffraction-limited Mid-infrared Integral Field Spectroscopy of Io's Volcanic Activity with ALES on the Large Binocular Telescope

    NASA Astrophysics Data System (ADS)

    Skrutskie, Michael F.; de Kleer, Katherine R.; Stone, Jordan; Conrad, Al; Davies, Ashley; de Pater, Imke; Leisenring, Jarron; Hinz, Philip; Skemer, Andrew; Veillet, Christian; Woodward, Charles E.; Ertel, Steve; Spalding, Eckhart

    2017-10-01

    The Arizona Lenslet for Exoplanet Spectroscopy (ALES) is an enhancement to the Large Binocular Telescope's mid-infrared imager, LMIRcam, that permits low-resolution (R~20) spectroscopy between 2.8 and 4.2 μm of every diffraction-limited resolution element in a 2.5"x2.5" field-of-view on a 2048x2048 HAWAII-2RG 5.2 μm-cutoff array. The 1" disk of Io, dotted with powerful self-luminous volcanic eruptions, provides an ideal target for ALES, where the single 8.4-meter aperture diffraction-limited scale for Io at opposition ranges from 240 kilometers (80 milliarcseconds) at 2.8 μm to 360 kilometers (120 milliarcseconds) at 4.2 μm. ALES provides the capability to assess the color temperature of each volcanic thermal emission site as well as map broadband absorbers such as SO2 frost. A monitoring campaign in the Spring 2017 semester provided two global snapshots of Io's volcanic activity with ALES as well as characterization of a new brightening episode at Loki Patera over four epochs between January and May 2017.

  16. The Neural Bases of Difficult Speech Comprehension and Speech Production: Two Activation Likelihood Estimation (ALE) Meta-Analyses

    ERIC Educational Resources Information Center

    Adank, Patti

    2012-01-01

    The role of speech production mechanisms in difficult speech comprehension is the subject of on-going debate in speech science. Two Activation Likelihood Estimation (ALE) analyses were conducted on neuroimaging studies investigating difficult speech comprehension or speech production. Meta-analysis 1 included 10 studies contrasting comprehension…

  17. High performance liquid chromatography with photo diode array for separation and analysis of naproxen and esomeprazole in presence of their chiral impurities: Enantiomeric purity determination in tablets.

    PubMed

    Ragab, Marwa A A; El-Kimary, Eman I

    2017-05-12

    A stereoselective high performance liquid chromatographic method with diode array detection (HPLC-DAD) was introduced for S-naproxen and esomeprazole determination in tablets. The separation was achieved on a Kromasil Cellucoat chiral column using a mobile phase consisting of hexane: isopropanol: trifluoroacetic acid (TFA) (90:9.9:0.1 v/v/v). The proposed system was found to be suitable for the enantioseparation of naproxen and omeprazole biologically active isomers. After optimization of the chromatographic conditions, resolution values of 3.84 and 2.17 could be obtained for naproxen and omeprazole isomers, respectively. The method was fully validated for the determination of S-isomers of each drug in their dosage form. Also, the enentiomeric purity was determined in commercial tablet containing S-naproxen and esomeprazole. The enantiomeric purity was calculated for each drug and the chiral impurities (R-isomers) could be determined at 1% level. The method was validated and good results with respect to linearity, precision, accuracy, selectivity and robustness were obtained. The limits of detection (LOD) and quantification (LOQ) were 2.00, 6.50 and 0.10, 0.35μgmL -1 for S-naproxen and esomeprazole, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Efficacy of naproxen with or without esomeprazole for pain and inflammation in patients after bilateral third molar extractions: A double blinded crossover study

    PubMed Central

    Weckwerth, Giovana M.; Simoneti, Luis F.; Zupelari-Gonçalves, Paulo; Calvo, Adriana M.; Brozoski, Daniel T.; Dionísio, Thiago J.; Torres, Elza A.; Lauris, José-Roberto P.; Faria, Flávio-Augusto C.

    2017-01-01

    Background Using a double-blinded randomized crossover design, this study aimed to evaluate acute postoperative pain management, swelling and trismus in 46 volunteers undergoing extractions of the two lower third molars, in similar positions, at two different appointments who consumed a tablet of either NE (naproxen 500 mg + esomepraz ole 20 mg) or only naproxen (500 mg) every 12 hours for 4 days. Material and Methods Parameters were analyzed: self-reported pain intensity using a visual analog scale (VAS) pre- and postoperative mouth opening; incidence, type and severity of adverse reactions; total quantity consumed of rescue medication; and pre- and postoperative swelling. Results Female volunteers reported significantly more postoperative pain at 1, 1.5, 2, 3 and 4hrs after surgery while also taking their first rescue medication at a time significantly earlier when consuming NE when compared to naproxen (3.7hrs and 6.7hrs). Conversely, no differences were found between each drug group in males. Conclusions In conclusion, throughout the entire study, pain was mild after using either drug in both men and women with pain scores on average well below 40mm (VAS), although in women naproxen improved acute postoperative pain management when compared to NE. Key words:Oral surgery, third molar, pain, naproxen, esomeprazole, NSAIDs. PMID:27918744

  19. Freeze drying of orally disintegrating tablets containing taste masked naproxen sodium granules in blisters.

    PubMed

    Stange, Ulrike; Führling, Christian; Gieseler, Henning

    2014-09-15

    Abstract Orally disintegrating tablets (ODTs) were freeze dried in blisters using the Lyostar® II SMART™ Freeze Dryer Technology. ODT formulations either without non-water soluble particles (placebo) or containing large fractions (717 mg) of taste-masked naproxen sodium (NaS) granules were freeze dried. The process data revealed differences between ODTs with and without embedded granules in the pressure rise curves as well as in the shelf (inlet) temperature adjustments during freeze-drying. Pressure rise curves of the placebo ODTs from eight hours process time showed no distinct temperature-dominated part, and the last optimization step of the shelf temperature to achieve -24.4 °C might be prone to errors. The final shelf temperature of ODTs containing granules was -23.3 °C. The detection of primary drying endpoints using SMART™ Technology or comparative pressure measurements was reliable for both ODT formulations, whereas the application of thermocouples resulted in premature endpoint indication. Product resistance of ODTs containing granules was generally elevated in comparison to ODTs without granules, but increased only slightly over the course of the drying process. In summary, the developed freeze-drying cycle was found applicable for production of elegant ODTs with incorporated taste masked NaS granules.

  20. [Photodegradation of naproxen in aqueous systems by UV irradiation: mechanism and toxicity of photolysis products].

    PubMed

    Ma, Du-juan; Liu, Guo-guang; Lü, Wen-ying; Yao, Kun; Zhou, Li-hua; Xie, Cheng-ping

    2013-05-01

    This paper studies the degradation mechanism, the reaction kinetics and the toxicity of photolysis products of naproxen in waters under UV irradiation (120 W mercury lamp) by quenching experiments of reactive oxygen species (ROS), oxygen concentration experiment and toxicity evaluation using Vibrio fischeri bacteria. The results demonstrated that NPX could be degraded effectively by UV irradiation and the photolysis pathways was the sum of the degradation by direct photolysis and self-sensitization via ROS, and the contribution rates of self-sensitized photodegradation were 0.1%, 80.2%, 35.7% via *OH, (1)O2, O2*-, respectively. The effect of oxygen concentration illustrated that dissolved oxygen had an inhibitory effect on the direct photodegradation of NPX, and the higher the oxygen content, the more obvious the inhibitory effect. The toxicity evaluation illustrated the formation of some intermediate products that were more toxic than NPX during the photodegradation of NPX. The process of NPX degradation in all cases could be fitted by the pseudo first-order kinetics model.

  1. Detection of naproxen and its metabolites in fish bile following intraperitoneal and aqueous exposure.

    PubMed

    Brozinski, Jenny-Maria; Lahti, Marja; Oikari, Aimo; Kronberg, Leif

    2011-06-01

    The anti-inflammatory drug naproxen (NPX) has been found as a micropollutant in river water downstream the discharge points of wastewater treatment plants (WWTP). In this study, rainbow trout (Oncorhynchus mykiss) was exposed to NXP and the uptake and metabolism of the drug was studied. Following exposure through intraperitoneal injection (i.p., 0.5 mg NPX/100 g fish biomass) and through water (1.6 μg L(-1)), the bile was collected and analyzed with various LC-MS/MS methods. The identification of the formed metabolites in i.p. injected fish was based on the exact mass determinations by a time-of-flight mass analyzer (Q-TOF-MS) and on the studies of fragments and fragmentation patterns of precursor ions by an ion trap mass analyzer (IT-MS). No matter the exposure route, the main metabolites were found to be acyl glucuronides of NPX and of 6-O-desmethylnaproxen. Also, unmetabolized NPX was detected in the bile. The total bioconcentration factors (BCF(total-bile)) of NPX and the metabolites in the bile of fish exposed through water ranged from 500 to 2,300. The findings suggest that fish living downstream WWTPs may take up NPX and metabolize the compound. Consequently, NPX and its metabolites in bile can be used to monitor the exposure of fish to NPX.

  2. Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid.

    PubMed

    Cleuvers, Michael

    2004-11-01

    The ecotoxicity of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, naproxen, and acetylsalicylic acid (ASA) has been evaluated using acute Daphnia and algal tests. Toxicities were relatively low, with half-maximal effective concentration (EC50) values obtained using Daphnia in the range from 68 to 166 mg L(-1) and from 72 to 626 mg L(-1) in the algal test. Acute effects of these substances seem to be quite improbable. The quantitative structure-activity relationships (QSAR) approach showed that all substances act by nonpolar narcosis; thus, the higher the n-octanol/water partitioning coefficient (log Kow) of the substances, the higher is their toxicity. Mixture toxicity of the compounds could be accurately predicted using the concept of concentration addition. Toxicity of the mixture was considerable, even at concentrations at which the single substances showed no or only very slight effects, with some deviations in the Daphnia test, which could be explained by incompatibility of the very steep dose-response curves and the probit analysis of the data. Because pharmaceuticals in the aquatic environment occur usually as mixtures, an accurate prediction of the mixture toxicity is indispensable for environmental risk assessment.

  3. Naproxen-imprinted xerogels in the micro- and nanospherical formsby emulsion technique.

    PubMed

    Ornelas, Mariana; Azenha, Manuel; Pereira, Carlos; Silva, A Fernando

    2015-11-27

    Naproxen-imprinted xerogels in the microspherical and nanospherical forms were prepared by W/O emulsion and microemulsion, respectively. The work evolved from a sol–gel mixture previously reported for bulk synthesis. It was relatively simple to convert the original sol–gel mixture to one amenable to emulsion technique. The microspheres thus produced presented mean diameter of 3.7 μm, surface area ranging 220–340 m2/g, selectivity factor 4.3 (against ibuprofen) and imprinting factor 61. A superior capacity (9.4 μmol/g) was found, when comparing with imprints obtained from similar pre-gelification mixtures. However, slow mass transfer kinetics was deduced from column efficiency results. Concerning the nanospherical format, which constituted the first example of the production of molecularly imprinted xerogels in that format by microemulsion technique, adapting the sol–gel mixture was troublesome. In the end, nanoparticles with diameter in the order of 10 nm were finally obtained, exhibiting good indications of an efficient molecular imprinting process. Future refinements are necessary to solve serious aggregation issues, before moving to more accurate characterization of the binding characteristics or to real applications of the nanospheres.

  4. Sorption, photodegradation, and chemical transformation of naproxen and ibuprofen in soils and water.

    PubMed

    Vulava, Vijay M; Cory, Wendy C; Murphey, Virginia L; Ulmer, Candice Z

    2016-09-15

    Pharmaceutically active compounds (PhACs) are released into the environment where they undergo soil sorption, photodegradation, and chemical transformation into structurally similar compounds. Here we report on studies of naproxen (NAP) and ibuprofen (IBP), two widely-used nonsteroidal anti-inflammatory drugs (NSAIDS), in soils and water. Organic matter (OM) was observed to play an important role in each of these processes. Sorption was observed to be stronger and nonlinear in higher OM soils while weaker but still significant in lower OM, higher clay soils; the amphiphilic nature of these two PhACs combined with the complex charged and nonpolar surfaces available in the soil was observed to control the sorption behavior. Simulated solar photodegradation rates of NAP and IBP in water were observed to change in the presence of humic acid or fulvic acid. Structural analogs of each compound were observed as the result of chemical transformation in both photoexposed aqueous solutions and non-photoexposed soil. Two of these transformation products were detected as both soil and photo transformation products for both PhACs. OM was observed to influence the chemical transformation of both pharmaceuticals. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Sustained-release of naproxen sodium from electrospun-aligned PLLA-PCL scaffolds.

    PubMed

    Lui, Yuan Siang; Lewis, Mark P; Loo, Say Chye Joachim

    2017-04-01

    Spontaneous tendon healing may result in reduced tissue functionality. In view of this, tissue engineering (TE) emerges as a promising approach in promoting proper tendon regeneration. However, unfavourable post-surgical adhesion formations restrict adequate tendon healing through the TE approach. Naproxen sodium (NPS), a non-steroidal anti-inflammatory drug (NSAID), has been demonstrated to prevent adhesions by inhibiting the inflammatory response. Therefore, in this study, various factors, such as polymer composition, i.e. different poly-l-lactic acid (PLLA):polycaprolactone (PCL) ratios, and percentage of water:hexafluoroisopropanol (HFIP; as co-solvent) ratios, were investigated to understand how these can influence the release of NPS from electrospun scaffolds. By adjusting the amount of water as the co-solvent, NPS could be released sustainably for as long as 2 weeks. Scaffold breaking strength was also enhanced with the addition of water as the co-solvent. This NPS-loaded scaffold showed no significant cytotoxicity, and L929 murine fibroblasts cultured on the scaffolds were able to proliferate and align along the fibre orientation. These scaffolds with desirable tendon TE characteristics would be promising candidates in achieving better tendon regeneration in vivo. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Novel organogels for topical delivery of naproxen: design, physicochemical characteristics and in vitro drug permeation.

    PubMed

    Osmałek, Tomasz; Milanowski, Bartłomiej; Froelich, Anna; Górska, Sylwia; Białas, Wojciech; Szybowicz, Mirosław; Kapela, Marcin

    2017-06-01

    Taking into account possible irritation of the skin upon contact with naproxen (NPX) crystals and lower bioavailability after administration of the suspended or ionized drug, the aim of the work was to design and characterize novel and easy-to-formulate gels with the entirely dissolved drug in the acidic form. The formulations contained ethanol, SynperonicTMPE/L 62 and Arlasolve® DMI or Transcutol®. Carbopol®940 was used as the thickener. The properties of organogels were compared with six market products. The rheological measurements included steady flow experiments and oscillatory analysis. The texture profile analysis was conducted to calculate the mechanistic parameters. The in vitro permeation studies were performed on SOTAX CE 7 smart apparatus with the application of Strat-M artificial membranes. The obtained organogels fulfilled the requirements for topical products in terms of consistency, uniformity, stability, drug dissolution and permeation. The permeation studies revealed distinct differences among the commercial hydrogels according to permeation coefficients (k P ), drug flux (J ss ) and average cumulative amount of NPX per area after 12 h (Q 12h ). The presented work clearly shows that the organogels can be proposed as an alternative for commercial products where NPX occurs in the form of crystals.

  7. Naproxen degradation test to monitor Trametes versicolor activity in solid-state bioremediation processes.

    PubMed

    Rodríguez-Rodríguez, Carlos E; Marco-Urrea, Ernest; Caminal, Gloria

    2010-07-15

    The white-rot fungus Trametes versicolor has been studied as a potential agent for the removal of environmental pollutants. For long-time solid-phase bioremediation systems a test is required to monitor the metabolic status of T. versicolor and its degradation capability at different stages. A biodegradation test based on the percentage of degradation of a spiked model pharmaceutical (anti-inflammatory naproxen) in 24 h (ND24) is proposed to monitor the removal of pharmaceuticals and personal care products in sewage sludge. ND24 is intended to act as a test complementary to ergosterol quantification as specific fungal biomarker, and laccase activity as extracellular oxidative capacity of T. versicolor. For samples collected over 45 d, ND24 values did not necessarily correlate with ergosterol or laccase amounts but in most cases, they were over 30% degradation, indicating that T. versicolor may be suitable for bioremediation of sewage sludge in the studied period. 2010 Elsevier B.V. All rights reserved.

  8. Study on numerical simulation of asymmetric structure aluminum profile extrusion based on ALE method

    NASA Astrophysics Data System (ADS)

    Chen, Kun; Qu, Yuan; Ding, Siyi; Liu, Changhui; Yang, Fuyong

    2018-05-01

    Using the HyperXtrude module based on the Arbitrary Lagrangian-Eulerian (ALE) finite element method, the paper simulates the steady extrusion process of the asymmetric structure aluminum die successfully. A verification experiment is carried out to verify the simulation results. Having obtained and analyzed the stress-strain field, temperature field and extruded velocity of the metal, it confirms that the simulation prediction results and the experimental schemes are consistent. The scheme of the die correction and optimization are discussed at last. By adjusting the bearing length and core thickness, adopting the structure of feeder plate protection, short shunt bridge in the upper die and three-level bonding container in the lower die to control the metal flowing, the qualified aluminum profile can be obtained.

  9. The neural basis of kinesthetic and visual imagery in sports: an ALE meta - analysis.

    PubMed

    Filgueiras, Alberto; Quintas Conde, Erick Francisco; Hall, Craig R

    2017-12-19

    Imagery is a widely spread technique in the sport sciences that entails the mental rehearsal of a given situation to improve an athlete's learning, performance and motivation. Two modalities of imagery are reported to tap into distinct brain structures, but sharing common components: kinesthetic and visual imagery. This study aimed to investigate the neural basis of those types of imagery with Activation Likelihood Estimation algorithm to perform a meta - analysis. A systematic search was used to retrieve only experimental studies with athletes or sportspersons. Altogether, nine studies were selected and an ALE meta - analysis was performed. Results indicated significant activation of the premotor, somatosensory cortex, supplementary motor areas, inferior and superior parietal lobule, caudate, cingulate and cerebellum in both imagery tasks. It was concluded that visual and kinesthetic imagery share similar neural networks which suggests that combined interventions are beneficial to athletes whereas separate use of those two modalities of imagery may seem less efficient from a neuropsychological approach.

  10. Surface tension models for a multi-material ALE code with AMR

    SciTech Connect

    Liu, Wangyi; Koniges, Alice; Gott, Kevin

    A number of surface tension models have been implemented in a 3D multi-physics multi-material code, ALE–AMR, which combines Arbitrary Lagrangian Eulerian (ALE) hydrodynamics with Adaptive Mesh Refinement (AMR). ALE–AMR is unique in its ability to model hot radiating plasmas, cold fragmenting solids, and most recently, the deformation of molten material. The surface tension models implemented include a diffuse interface approach with special numerical techniques to remove parasitic flow and a height function approach in conjunction with a volume-fraction interface reconstruction package. These surface tension models are benchmarked with a variety of test problems. In conclusion, based on the results, themore » height function approach using volume fractions was chosen to simulate droplet dynamics associated with extreme ultraviolet (EUV) lithography.« less

  11. Surface tension models for a multi-material ALE code with AMR

    DOE PAGES

    Liu, Wangyi; Koniges, Alice; Gott, Kevin; ...

    2017-06-01

    A number of surface tension models have been implemented in a 3D multi-physics multi-material code, ALE–AMR, which combines Arbitrary Lagrangian Eulerian (ALE) hydrodynamics with Adaptive Mesh Refinement (AMR). ALE–AMR is unique in its ability to model hot radiating plasmas, cold fragmenting solids, and most recently, the deformation of molten material. The surface tension models implemented include a diffuse interface approach with special numerical techniques to remove parasitic flow and a height function approach in conjunction with a volume-fraction interface reconstruction package. These surface tension models are benchmarked with a variety of test problems. In conclusion, based on the results, themore » height function approach using volume fractions was chosen to simulate droplet dynamics associated with extreme ultraviolet (EUV) lithography.« less

  12. The neuronal correlates of intranasal trigeminal function – An ALE meta-analysis of human functional brain imaging data

    PubMed Central

    Albrecht, Jessica; Kopietz, Rainer; Frasnelli, Johannes; Wiesmann, Martin; Hummel, Thomas; Lundström, Johan N.

    2009-01-01

    Almost every odor we encounter in daily life has the capacity to produce a trigeminal sensation. Surprisingly, few functional imaging studies exploring human neuronal correlates of intranasal trigeminal function exist, and results are to some degree inconsistent. We utilized activation likelihood estimation (ALE), a quantitative voxel-based meta-analysis tool, to analyze functional imaging data (fMRI/PET) following intranasal trigeminal stimulation with carbon dioxide (CO2), a stimulus known to exclusively activate the trigeminal system. Meta-analysis tools are able to identify activations common across studies, thereby enabling activation mapping with higher certainty. Activation foci of nine studies utilizing trigeminal stimulation were included in the meta-analysis. We found significant ALE scores, thus indicating consistent activation across studies, in the brainstem, ventrolateral posterior thalamic nucleus, anterior cingulate cortex, insula, precentral gyrus, as well as in primary and secondary somatosensory cortices – a network known for the processing of intranasal nociceptive stimuli. Significant ALE values were also observed in the piriform cortex, insula, and the orbitofrontal cortex, areas known to process chemosensory stimuli, and in association cortices. Additionally, the trigeminal ALE statistics were directly compared with ALE statistics originating from olfactory stimulation, demonstrating considerable overlap in activation. In conclusion, the results of this meta-analysis map the human neuronal correlates of intranasal trigeminal stimulation with high statistical certainty and demonstrate that the cortical areas recruited during the processing of intranasal CO2 stimuli include those outside traditional trigeminal areas. Moreover, through illustrations of the considerable overlap between brain areas that process trigeminal and olfactory information; these results demonstrate the interconnectivity of flavor processing. PMID:19913573

  13. Flocculation in ale brewing strains of Saccharomyces cerevisiae: re-evaluation of the role of cell surface charge and hydrophobicity.

    PubMed

    Holle, Ann Van; Machado, Manuela D; Soares, Eduardo V

    2012-02-01

    Flocculation is an eco-friendly process of cell separation, which has been traditionally exploited by the brewing industry. Cell surface charge (CSC), cell surface hydrophobicity (CSH) and the presence of active flocculins, during the growth of two (NCYC 1195 and NCYC 1214) ale brewing flocculent strains, belonging to the NewFlo phenotype, were examined. Ale strains, in exponential phase of growth, were not flocculent and did not present active flocculent lectins on the cell surface; in contrast, the same strains, in stationary phase of growth, were highly flocculent (>98%) and presented a hydrophobicity of approximately three to seven times higher than in exponential phase. No relationship between growth phase, flocculation and CSC was observed. For comparative purposes, a constitutively flocculent strain (S646-1B) and its isogenic non-flocculent strain (S646-8D) were also used. The treatment of ale brewing and S646-1B strains with pronase E originated a loss of flocculation and a strong reduction of CSH; S646-1B pronase E-treated cells displayed a similar CSH as the non-treated S646-8D cells. The treatment of the S646-8D strain with protease did not reduce CSH. In conclusion, the increase of CSH observed at the onset of flocculation of ale strains is a consequence of the presence of flocculins on the yeast cell surface and not the cause of yeast flocculation. CSH and CSC play a minor role in the auto-aggregation of the ale strains since the degree of flocculation is defined, primarily, by the presence of active flocculins on the yeast cell wall.

  14. Implementation errors in the GingerALE Software: Description and recommendations.

    PubMed

    Eickhoff, Simon B; Laird, Angela R; Fox, P Mickle; Lancaster, Jack L; Fox, Peter T

    2017-01-01

    Neuroscience imaging is a burgeoning, highly sophisticated field the growth of which has been fostered by grant-funded, freely distributed software libraries that perform voxel-wise analyses in anatomically standardized three-dimensional space on multi-subject, whole-brain, primary datasets. Despite the ongoing advances made using these non-commercial computational tools, the replicability of individual studies is an acknowledged limitation. Coordinate-based meta-analysis offers a practical solution to this limitation and, consequently, plays an important role in filtering and consolidating the enormous corpus of functional and structural neuroimaging results reported in the peer-reviewed literature. In both primary data and meta-analytic neuroimaging analyses, correction for multiple comparisons is a complex but critical step for ensuring statistical rigor. Reports of errors in multiple-comparison corrections in primary-data analyses have recently appeared. Here, we report two such errors in GingerALE, a widely used, US National Institutes of Health (NIH)-funded, freely distributed software package for coordinate-based meta-analysis. These errors have given rise to published reports with more liberal statistical inferences than were specified by the authors. The intent of this technical report is threefold. First, we inform authors who used GingerALE of these errors so that they can take appropriate actions including re-analyses and corrective publications. Second, we seek to exemplify and promote an open approach to error management. Third, we discuss the implications of these and similar errors in a scientific environment dependent on third-party software. Hum Brain Mapp 38:7-11, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. The impact of different ale brewer's yeast strains on the proteome of immature beer.

    PubMed

    Berner, Torben Sune; Jacobsen, Susanne; Arneborg, Nils

    2013-09-30

    It is well known that brewer's yeast affects the taste and aroma of beer. However, the influence of brewer's yeast on the protein composition of beer is currently unknown. In this study, changes of the proteome of immature beer, i.e. beer that has not been matured after fermentation, by ale brewer's yeast strains with different abilities to degrade fermentable sugars were investigated. Beers were fermented from standard hopped wort (13° Plato) using two ale brewer's yeast (Saccharomyces cerevisiae) strains with different attenuation degrees. Both immature beers had the same alcohol and protein concentrations. Immature beer and unfermented wort proteins were analysed by 2-DE and compared in order to determine protein changes arising from fermentation. Distinct protein spots in the beer and wort proteomes were identified using Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and MS/MS and revealed common beer proteins, such as lipid transfer proteins (LTP1 and LTP2), protein Z and amylase-protease inhibitors. During fermentation, two protein spots, corresponding to LTP2, disappeared, while three protein spots were exclusively found in beer. These three proteins, all derived from yeast, were identified as cell wall associated proteins, that is Exg1 (an exo-β-1,3-glucanase), Bgl2 (an endo-β-1,2-glucanase), and Uth1 (a cell wall biogenesis protein). Yeast strain dependent changes in the immature beer proteome were identified, i.e. Bgl2 was present in beer brewed with KVL011, while lacking in WLP001 beer.

  16. The impact of different ale brewer’s yeast strains on the proteome of immature beer

    PubMed Central

    2013-01-01

    Background It is well known that brewer’s yeast affects the taste and aroma of beer. However, the influence of brewer’s yeast on the protein composition of beer is currently unknown. In this study, changes of the proteome of immature beer, i.e. beer that has not been matured after fermentation, by ale brewer’s yeast strains with different abilities to degrade fermentable sugars were investigated. Results Beers were fermented from standard hopped wort (13° Plato) using two ale brewer’s yeast (Saccharomyces cerevisiae) strains with different attenuation degrees. Both immature beers had the same alcohol and protein concentrations. Immature beer and unfermented wort proteins were analysed by 2-DE and compared in order to determine protein changes arising from fermentation. Distinct protein spots in the beer and wort proteomes were identified using Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and MS/MS and revealed common beer proteins, such as lipid transfer proteins (LTP1 and LTP2), protein Z and amylase-protease inhibitors. During fermentation, two protein spots, corresponding to LTP2, disappeared, while three protein spots were exclusively found in beer. These three proteins, all derived from yeast, were identified as cell wall associated proteins, that is Exg1 (an exo-β-1,3-glucanase), Bgl2 (an endo-β-1,2-glucanase), and Uth1 (a cell wall biogenesis protein). Conclusion Yeast strain dependent changes in the immature beer proteome were identified, i.e. Bgl2 was present in beer brewed with KVL011, while lacking in WLP001 beer. PMID:24079909

  17. Application of the ALE and MBE Methods to the Growth of Layered Hg sub x Cd sub 1-x Te Films.

    DTIC Science & Technology

    1986-09-26

    films / We have studied the applicability of the Atomic Layer Epitaxy (ALE, vee Ref. -1pand Molecular Beam Epitaxy (MBE) ito growth of Hg2 Cdi- ,Te...thin- films throughout the composition range 0 x $ 0.8. The progress of the Contract has been reported periodically in five interim reports. This final...I separate sources) yielded films with high x values. On the grounds of these observations we do not find ALE suitable for growth of HgCdTe. 2) ALE

  18. The Influence of Hydrophilic Interactions on the Sorption and Mobility of Naproxen at Environmentally-Relevant Concentrations

    NASA Astrophysics Data System (ADS)

    Muller, K.; Ramsburg, C. A.

    2011-12-01

    Managed underground storage of reclaimed wastewater is currently one viable option for meeting increasing demands on water resources, yet the attenuation of many emerging contaminants within the subsurface environment is not well understood. Pharmaceuticals are of particular concern due to the rapid increase in development and use of these compounds, observations of incomplete removal during wastewater treatment, and emerging concerns over ecosystem effects. Assessment of the subsurface attenuation of pharmaceuticals is difficult because the compounds are polar, pH-active, and present at low-concentration (ng/L). Predictions of sorption that only consider hydrophobic interactions with soil organic matter may not fully describe the extent to which reversible sequestration influences pharmaceutical attenuation. In fact, hydrophilic interactions (i.e. ion exchange, cation-induced sorption, hydrogen bonding, etc) may represent important contributions to total sorption, especially when aqueous solutes are present at low concentration. Here we assess the sorption of naproxen - an acidic pharmaceutical - to three subsurface materials using equilibrium batch experiments and 1-d column experiments. Subsurface materials evaluated include Ottawa sand (quartz with negligible organic carbon and negligible iron oxide), Aplite sand (quartz and feldspar with negligible organic carbon, 0.2% wt iron oxide), and a Hinckley series silty-sand (quartz and feldspar with 0.95% wt organic carbon, and 0.4% wt iron oxides). Sorption of naproxen to the Ottawa sand was negligible and did not result in measurable retardation when naproxen was introduced to the porous medium at a concentration of 275 ng/L. Batch experiments suggest that Aplite sand offers quantifiable interaction (52% of the mass introduced is associated with the solid phase when the aqueous concentration is 1000 ng/L and the solid to liquid ratio is 1.4:1 v/v); however, column data are indicative of markedly less interaction

  19. Combination of atorvastatin with sulindac or naproxen profoundly inhibits colonic adenocarcinomas by suppressing the p65/β-catenin/cyclin D1 signaling pathway in rats

    PubMed Central

    Suh, Nanjoo; Reddy, Bandaru S.; DeCastro, Andrew; Paul, Shiby; Lee, Hong Jin; Smolarek, Amanda K.; So, Jae Young; Simi, Barbara; Wang, Chung Xiou; Janakiram, Naveena B.; Steele, Vernon; Rao, Chinthalapally V.

    2011-01-01

    Evidence supports the protective role of non-steroidal anti-inflammatory drugs (NSAIDs) and statins against colon cancer. Experiments were designed to evaluate the efficacies atorvastatin and NSAIDs administered individually and in combination against colon tumor formation. F344 rats were fed AIN-76A diet and colon tumors were induced with azoxymethane (AOM). One week after the second AOM-treatment groups of rats were fed diets containing atorvastatin (200 ppm), sulindac (100 ppm) or naproxen (150 ppm), or their combinations with low-dose atorvastatin (100 ppm) for 45 weeks. Administration of atorvastatin at 200 ppm significantly suppressed both adenocarcinoma incidence (52% reduction, p=0.005) and multiplicity (58% reduction, p=0.008). Most importantly, colon tumor multiplicities were profoundly decreased (80–85% reduction, p<0.0001) when given low-dose atorvastatin with either sulindac or naproxen. Also, a significant inhibition of colon tumor incidence was observed when given a low-dose atorvastatin with either sulindac (p=0.001) or naproxen (p =0.0005). Proliferation markers, proliferating cell nuclear antigen, cyclin D1 and β-catenin in tumors of rats exposed to sulindac, naproxen, atorvastatin, and/or combinations showed a significant suppression. Importantly, colon adenocarcinomas from atorvastatin and NSAIDs fed animals showed reduced key inflammatory markers, inducible nitric oxide synthase and cyclooxygenase-2, phospho-p65, as well as inflammatory cytokines, TNF-α, IL-1β, and IL-4. Overall, this is the first report on the combination treatment using low-dose atorvastatin with either low dose sulindac or naproxen, which greatly suppress the colon adenocarcinoma incidence and multiplicity. Our results suggest that low-dose atorvastatin with sulindac or naproxen might potentially be useful combinations for colon cancer prevention in humans. PMID:21764859

  20. A preclinical physiological assay to test modulation of knee joint pain in the spinal cord: effects of oxycodone and naproxen.

    PubMed

    Miranda, Jason A; Stanley, Phil; Gore, Katrina; Turner, Jamie; Dias, Rebecca; Rees, Huw

    2014-01-01

    Sensory processing in the spinal cord during disease states can reveal mechanisms for novel treatments, yet very little is known about pain processing at this level in the most commonly used animal models of articular pain. Here we report a test of the prediction that two clinically effective compounds, naproxen (an NSAID) and oxycodone (an opiate), are efficacious in reducing the response of spinal dorsal horn neurons to noxious knee joint rotation in the monosodium iodoacetate (MIA) sensitized rat. The overall objective for these experiments was to develop a high quality in vivo electrophysiology assay to confidently test novel compounds for efficacy against pain. Given the recent calls for improved preclinical experimental quality we also developed and implemented an Assay Capability Tool to determine the quality of our assay and ensure the quality of our results. Spinal dorsal horn neurons receiving input from the hind limb knee joint were recorded in anesthetized rats 14 days after they were sensitized with 1 mg of MIA. Intravenous administered oxycodone and naproxen were each tested separately for their effects on phasic, tonic, ongoing and afterdischarge action potential counts in response to innocuous and noxious knee joint rotation. Oxycodone reduced tonic spike counts more than the other measures, doing so by up to 85%. Tonic counts were therefore designated the primary endpoint when testing naproxen which reduced counts by up to 81%. Both reductions occurred at doses consistent with clinically effective doses for osteoarthritis. These results demonstrate that clinically effective doses of standard treatments for osteoarthritis reduce pain processing measured at the level of the spinal cord for two different mechanisms. The Assay Capability Tool helped to guide experimental design leading to a high quality and robust preclinical assay to use in discovering novel treatments for pain.

  1. Native and microwave-modified Terminalia mantaly gums as sustained-release and bioadhesive excipients in naproxen matrix tablet formulations.

    PubMed

    Odeniyi, Michael Ayodele; Oyedokun, Babatunde Mukhtar; Bamiro, Oluyemisi Adebowale

    2017-01-01

    Hydrophilic polymers provide a means of sustaining drug delivery. Native gums may be limited in function, but modification may improve their activity. The aim of the study was to evaluate native and modified forms of Terminalia mantaly gum for their sustained-release and bioadhesive properties. The native gum (NTM) was modified by microwave irradiation for 20 seconds (MTM20) and 60 seconds (MTM60) and characterized using microscopy, Fourier transform infrared spectroscopy (FTIR) and packing properties. The effects of the thermally induced molecular reorientation were determined. Tablet formulations of naproxen were produced by direct compression. The mechanical, bioadhesive and release properties of the formulations were determined. Irradiation of NTM improved the gum's flow properties, resulting in Carr's Index and Hausner's ratios lower than 16% and 1.25, respectively. Swelling studies showed that MTM20 and MTM60 had lower water absorption capacity and swelling index values, while packing properties improved upon irradiation, as depicted by lower tapped density values. FTIR spectra of samples showed that the irradiated gums were distinct from the native gums and did not interact with naproxen sodium. The gum's mechanical properties improved with MTM20 and MTM60 and sustained-release action of up 12 h was obtained. Inclusion of hydroxypropyl methylcellulose (HPMC) in the tablet formulations proved critical for bioadhesion. Microwave irradiation of native Terminalia mantaly gum improved the flow, mechanical and sustained-release properties of Naproxen tablets, and the addition of HPMC increased bioadhesion properties. The tablet properties of the native gum were significantly improved after 20 s of microwave irradiation.

  2. Multi-Modal Preemptive Analgesia With Pregabalin, Acetaminophen, Naproxen, and Dextromethorphan in Radical Neck Dissection Surgery: A Randomized Clinical Trial

    PubMed Central

    Amiri, Hamid Reza; Mirzaei, Mojtaba; Beig Mohammadi, Mohammad Taghi; Tavakoli, Farhad

    2016-01-01

    Background Preemptive analgesia may be considered as a method not only to alleviate postoperative pain but also to decrease analgesic consumption. Different regimens are suggested, but there is currently no standard. Objectives The aim was to measure the efficacy of preemptive analgesia with pregabalin, acetaminophen, naproxen, and dextromethorphan in radical neck dissection surgery for reducing the intensity of pain and morphine consumption. Patients and Methods This study was conducted as a randomized double-blind clinical trial. Eighty adult patients (18 to 60 years of age) under the American society of anesthesiologists (ASA) physical status I and II undergoing elective radical neck dissection were enrolled. Patients were randomized into two groups of 40 with a simple randomization method. The case group received a combination of 15 mg/kg acetaminophen, 2.5 mg/kg pregabalin, 7 mg/kg naproxen, and 0.3 mg/kg dextromethorphan administered orally one hour prior to surgery. Postoperative pain was assessed with the universal pain assessment tool (UPAT) at 0, 2, 4, 6, 12, and 24 hours after surgery. Subjects received morphine based on postoperative pain control protocol. Total administered morphine doses were noted. Results Postoperative pain rates at 0, 2, 4, 6, 12, and 24 hours after surgery were significantly lower for the case group than the control group (P values = 0.014, 0.003, 0.00, 0.00, and 0.00, respectively). Total morphine doses for the preemptive analgesia group were 45% lower than those of the other group. Side effects were similar for both groups. Conclusions A single preoperative oral dose of pregabalin, acetaminophen, dextromethorphan, and naproxen one hour before surgery is an effective method for reducing postoperative pain and morphine consumption in patients undergoing radical neck dissection. PMID:27843771

  3. Naproxen, paracetamol and pamabrom versus paracetamol, pyrilamine and pamabrom in primary dysmenorrhea: a randomized, double-blind clinical trial.

    PubMed

    Ortiz, Mario I; Murguía-Cánovas, Gabriela; Vargas-López, Laura C; Silva, Rodolfo; González-de la Parra, Mario

    2016-10-24

    Dysmenorrhea is caused by the discharge of prostaglandins into the uterine tissue; therefore, non-steroidal anti-inflammatory drugs (NSAIDs) are the established initial therapy for dysmenorrhea. Dysmenorrhea therapy may include the administration of drug monotherapy or combination therapy. However, clinical scientific evidence on the efficacy of medications with two or three drugs combined is scarce or nonexistent. To evaluate and compare the efficacy and safety of two oral fixed-dose combinations for the relief of the symptoms of primary dysmenorrhea among Mexican women. One of the combinations is widely used in Mexico (paracetamol, pyrilamine and pamabrom) and the selected comparison was a medication with naproxen sodium, paracetamol and pamabrom based on the pathophysiology of primary dysmenorrhea. This was a single-centre, double blind, experimental, parallel group, randomized trial. Female patients with primary dysmenorrhea, older than 17 years and with pain intensity greater than 45 mm on a visual analogue scale, were included. The patients were then randomized to receive tablets with naproxen sodium, paracetamol and pamabrom or tablets with paracetamol, pyrilamine and pamabrom for one menstrual cycle. Patient evaluations of symptomatology and pain intensity were recorded throughout one menstrual period. Descriptive and inferential statistical analyses were utilized. An intention-to-treat population of 91 women, with a mean age of 21.3 ± 3.2 years, received paracetamol, pyrilamine and pamabrom tablets, and 98 participants, with a mean age of 21.0 ± 3.2 years, received naproxen sodium, paracetamol and pamabrom tablets. The participants’ assessments of pain on the Visual Analogue Scale during the menstrual cycle demonstrated a significant reduction in both treatment groups (p<0.05). There is no significant difference in efficacy between both groups (p>0.05). The results showed that both drug combinations were not different in reducing dysmenorrheic pain

  4. A Preclinical Physiological Assay to Test Modulation of Knee Joint Pain in the Spinal Cord: Effects of Oxycodone and Naproxen

    PubMed Central

    Miranda, Jason A.; Stanley, Phil; Gore, Katrina; Turner, Jamie; Dias, Rebecca; Rees, Huw

    2014-01-01

    Sensory processing in the spinal cord during disease states can reveal mechanisms for novel treatments, yet very little is known about pain processing at this level in the most commonly used animal models of articular pain. Here we report a test of the prediction that two clinically effective compounds, naproxen (an NSAID) and oxycodone (an opiate), are efficacious in reducing the response of spinal dorsal horn neurons to noxious knee joint rotation in the monosodium iodoacetate (MIA) sensitized rat. The overall objective for these experiments was to develop a high quality in vivo electrophysiology assay to confidently test novel compounds for efficacy against pain. Given the recent calls for improved preclinical experimental quality we also developed and implemented an Assay Capability Tool to determine the quality of our assay and ensure the quality of our results. Spinal dorsal horn neurons receiving input from the hind limb knee joint were recorded in anesthetized rats 14 days after they were sensitized with 1 mg of MIA. Intravenous administered oxycodone and naproxen were each tested separately for their effects on phasic, tonic, ongoing and afterdischarge action potential counts in response to innocuous and noxious knee joint rotation. Oxycodone reduced tonic spike counts more than the other measures, doing so by up to 85%. Tonic counts were therefore designated the primary endpoint when testing naproxen which reduced counts by up to 81%. Both reductions occurred at doses consistent with clinically effective doses for osteoarthritis. These results demonstrate that clinically effective doses of standard treatments for osteoarthritis reduce pain processing measured at the level of the spinal cord for two different mechanisms. The Assay Capability Tool helped to guide experimental design leading to a high quality and robust preclinical assay to use in discovering novel treatments for pain. PMID:25157947

  5. A randomized, clinical trial to assess the relative efficacy and tolerability of two doses of etoricoxib versus naproxen in patients with ankylosing spondylitis.

    PubMed

    Balazcs, Eva; Sieper, Joachim; Bickham, Kara; Mehta, Anish; Frontera, Nancy; Stryszak, Paul; Popmihajlov, Zoran; Peloso, Paul M

    2016-10-13

    This study evaluated two doses of etoricoxib (60 and 90 mg) vs. naproxen 1000 mg in subjects with ankylosing spondylitis (AS). This was a 2-part, double-blind, active comparator-controlled non-inferiority study in subjects ≥18 years of age with AS. In Part I, subjects were randomized to naproxen 1000 mg; etoricoxib 60 mg, and 90 mg. In Part II, naproxen and etoricoxib 90 mg subjects continued on the same treatment; subjects on etoricoxib 60 mg either continued on 60 mg or escalated to 90 mg. Part I (6 weeks) assessed the efficacy of A) etoricoxib 60 mg vs. naproxen and B) 90 mg vs. naproxen according to the time-weighted average change from baseline in Spinal Pain Intensity (SPI; 0-100 mm VAS) (primary endpoint). The non-inferiority margin was set at 8 mm for SPI. In Part II (20 weeks) we evaluated the potential benefit of increasing from 60 to 90 mg (predefined minimum clinically important difference = 6 mm in SPI) for inadequate responders (<50 % improvement from baseline in SPI) on etoricoxib 60 mg in Part I. In total, 1015 subjects were randomized to receive etoricoxib 60 mg (N = 702), etoricoxib 90 mg (N = 156), and naproxen 1000 mg (N = 157); 70.9 % were male and the mean age was 45.2 years. There were 919 subjects who completed Part I and all continued to Part II. In Part I, SPI change was non-inferior for both etoricoxib doses vs. naproxen. In both Part I and II, the incidence of adverse events (AEs), drug-related AEs, and serious adverse events (SAEs) were similar between the 3 treatment groups. Both doses of etoricoxib were non-inferior to naproxen. All treatments were well tolerated. Etoricoxib 60 and 90 mg effectively control pain in patients with AS, with 60 mg once daily as the lowest effective dose for most patients. Clinical Trials Registry # NCT01208207 . Registered on 22 September 2010.

  6. Removal of ibuprofen, naproxen and carbamazepine in aqueous solution onto natural clay: equilibrium, kinetics, and thermodynamic study

    NASA Astrophysics Data System (ADS)

    Khazri, Hassen; Ghorbel-Abid, Ibtissem; Kalfat, Rafik; Trabelsi-Ayadi, Malika

    2017-10-01

    This study aimed to describe the adsorption of three pharmaceuticals compounds (ibuprofen, naproxen and carbamazepine) onto natural clay on the basis of equilibrium parameters such as a function of time, effect of pH, varying of the concentration and the temperature. Adsorption kinetic data were modeled using the Lagergren's first-order and the pseudo-second-order kinetic equations. The kinetic results of adsorption are described better using the pseudo-second order model. The isotherm results were tested in the Langmuir, Freundlich and Dubinin-Radushkevich models. The thermodynamic parameters obtained indicate that the adsorption of pharmaceuticals on the clay is a spontaneous and endothermic process.

  7. The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis.

    PubMed

    Tracy, T S; Krohn, K; Jones, D R; Bradley, J D; Hall, S D; Brater, D C

    1992-01-01

    We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.

  8. Ultrasonic degradation of acetaminophen and naproxen in the presence of single-walled carbon nanotubes.

    PubMed

    Im, Jong-Kwon; Heo, Jiyong; Boateng, Linkel K; Her, Namguk; Flora, Joseph R V; Yoon, Jaekyung; Zoh, Kyung-Duk; Yoon, Yeomin

    2013-06-15

    Ultrasonic (US) and single-walled carbon nanotube (SWNT)-catalyzed ultrasonic (US/SWNT) degradation of a pharmaceutical (PhAC) mixture of acetaminophen (AAP) and naproxen (NPX) used as analgesics was carried out in water. In the absence of SWNTs, maximum degradations of AAP and NPX occurred at a high frequency (1000 kHz) and under acidic conditions (pH 3) and different solution temperatures (25 °C at 28 kHz and 35 °C at 1000 kHz) during US reactions. Rapid degradation of PhACs occurred within 10 min at 28 kHz (44.5% for AAP; 90.3% for NPX) and 1000 kHz (39.2% for AAP; 74.8% for NPX) at a SWNT concentration of 45 mgL(-1) under US/SWNT process, compared with 28 kHz (5.2% for AAP; 10.6% for NPX) and 1000 kHz (29.1% for AAP; 46.2% for NPX) under US process. Degradation was associated with the dispersion of SWNTs; small particles acted as nuclei during US reactions, enhancing the H2O2 production yield. NPX removal was greater than AAP removal under all US-induced reaction and SWNT adsorption conditions, which is governed by the chemical properties of PhACs. Based on the results, the optimal treatment performance was observed at 28 kHz with 45 mgL(-1) SWNTs (US/SWNT) within 10 min. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Ion-exchange selectivity of diclofenac, ibuprofen, ketoprofen, and naproxen in ureolyzed human urine.

    PubMed

    Landry, Kelly A; Sun, Peizhe; Huang, Ching-Hua; Boyer, Treavor H

    2015-01-01

    This research advances the knowledge of ion-exchange of four non-steroidal anti-inflammatory drugs (NSAIDs) - diclofenac (DCF), ibuprofen (IBP), ketoprofen (KTP), and naproxen (NPX) - and one analgesic drug-paracetamol (PCM) - by strong-base anion exchange resin (AER) in synthetic ureolyzed urine. Freundlich, Langmuir, Dubinin-Astakhov, and Dubinin-Radushkevich isotherm models were fit to experimental equilibrium data using nonlinear least squares method. Favorable ion-exchange was observed for DCF, KTP, and NPX, whereas unfavorable ion-exchange was observed for IBP and PCM. The ion-exchange selectivity of the AER was enhanced by van der Waals interactions between the pharmaceutical and AER as well as the hydrophobicity of the pharmaceutical. For instance, the high selectivity of the AER for DCF was due to the combination of Coulombic interactions between quaternary ammonium functional group of resin and carboxylate functional group of DCF, van der Waals interactions between polystyrene resin matrix and benzene rings of DCF, and possibly hydrogen bonding between dimethylethanol amine functional group side chain and carboxylate and amine functional groups of DCF. Based on analysis of covariance, the presence of multiple pharmaceuticals did not have a significant effect on ion-exchange removal when the NSAIDs were combined in solution. The AER reached saturation of the pharmaceuticals in a continuous-flow column at varying bed volumes following a decreasing order of DCF > NPX ≈ KTP > IBP. Complete regeneration of the column was achieved using a 5% (m/m) NaCl, equal-volume water-methanol solution. Results from multiple treatment and regeneration cycles provide insight into the practical application of pharmaceutical ion-exchange in ureolyzed urine using AER.

  10. Kinetic and mechanistic aspects of hydroxyl radical‒mediated degradation of naproxen and reaction intermediates.

    PubMed

    Luo, Shuang; Gao, Lingwei; Wei, Zongsu; Spinney, Richard; Dionysiou, Dionysios D; Hu, Wei-Ping; Chai, Liyuan; Xiao, Ruiyang

    2018-06-15

    Hydroxyl radical ( • OH) based advanced oxidation technologies (AOTs) are effective for removing non‒steroidal anti-inflammatory drugs (NSAIDs) during water treatment. In this study, we systematically investigated the degradation kinetics of naproxen (NAP), a representative NSAID, with a combination of experimental and theoretical approaches. The second-order rate constant (k) of • OH oxidation of NAP was measured to be (4.32 ± 0.04) × 10 9  M -1  s -1 , which was in a reasonable agreement with transition state theory calculated k value (1.08 × 10 9  M -1  s -1 ) at SMD/M05-2X/6-311++G**//M05-2X/6-31+G** level of theory. The calculated result revealed that the dominant reaction intermediate is 2‒(5‒hydroxy‒6‒methoxynaphthalen‒2‒yl)propanoic acid (HMNPA) formed via radical adduct formation pathway, in which • OH addition onto the ortho site of the methoxy-substituted benzene ring is the most favorable pathway for the NAP oxidation. We further investigated the subsequent • OH oxidation of HMNPA via a kinetic modelling technique. The k value of the reaction of HMNPA and • OH was determined to be 2.22 × 10 9  M -1  s -1 , exhibiting a similar reactivity to the parent NAP. This is the first study on the kinetic and mechanistic aspects of NAP and its reaction intermediates. The current results are valuable in future study evaluating and extending the application of • OH based AOTs to degrade NAP and other NSAIDs of concern in water treatment plants. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Binding of naproxen enantiomers to human serum albumin studied by fluorescence and room-temperature phosphorescence

    NASA Astrophysics Data System (ADS)

    Lammers, Ivonne; Lhiaubet-Vallet, Virginie; Ariese, Freek; Miranda, Miguel A.; Gooijer, Cees

    2013-03-01

    The interaction of the enantiomers of the non-steroidal anti-inflammatory drug naproxen (NPX) with human serum albumin (HSA) has been investigated using fluorescence and phosphorescence spectroscopy in the steady-state and time-resolved mode. The absorption, fluorescence excitation, and fluorescence emission spectra of (S)-NPX and (R)-NPX differ in shape in the presence of HSA, indicating that these enantiomers experience a different environment when bound. In solutions containing 0.2 M KI, complexation with HSA results in a strongly increased NPX fluorescence intensity and a decreased NPX phosphorescence intensity due to the inhibition of the collisional interaction with the heavy atom iodide. Fluorescence intensity curves obtained upon selective excitation of NPX show 8-fold different slopes for bound and free NPX. No significant difference in the binding constants of (3.8 ± 0.6) × 105 M-1 for (S)-NPX and (3.9 ± 0.6) × 105 M-1 for (R)-NPX was found. Furthermore, the addition of NPX quenches the phosphorescence of the single tryptophan in HSA (Trp-214) based on Dexter energy transfer. The short-range nature of this mechanism explains the upward curvature of the Stern-Volmer plot observed for HSA: At low concentrations NPX binds to HSA at a distance from Trp-214 and no quenching occurs, whereas at high NPX concentrations the phosphorescence intensity decreases due to dynamic quenching by NPX diffusing into site I from the bulk solution. The dynamic quenching observed in the Stern-Volmer plots based on the longest phosphorescence lifetime indicates an overall binding constant to HSA of about 3 × 105 M-1 for both enantiomers.

  12. Tuberculose péritonéale pseudo tumorale mimant un cancer ovarien: un diagnostic différentiel important à considérer

    PubMed Central

    Moukit, Mounir; Fadel, Fatimazahra Ait El; Kouach, Jaouad; Babahabib, Abdellah; Dehayni, Mohammed; Rahali, Driss Moussaoui

    2016-01-01

    La tuberculose est une maladie infectieuse curable qui peut simuler dans sa localisation péritonéale un cancer ovarien avancé conduisant ainsi à une chirurgie étendue et inutile souvent chez des femmes en âge de reproduction. Nous rapportons un nouveau cas de tuberculose péritonéale pseudo tumorale chez une patiente âgée de 43 ans chez qui le diagnostic d’un cancer ovarien avec carcinose péritonéale avait été suspecté. La laparotomie exploratrice avec examen histologique extemporané ont permis de confirmer le diagnostic de tuberculose péritonéale. La patiente a bien répondu au traitement antituberculeux selon le protocole 2ERHZ/4RH. PMID:28292155

  13. Comparison of the pharmacokinetics and tolerability of HCP1004 (a fixed-dose combination of naproxen and esomeprazole strontium) and VIMOVO® (a marketed fixed-dose combination of naproxen and esomeprazole magnesium) in healthy volunteers

    PubMed Central

    Choi, YoonJung; Han, HyeKyung; Shin, Dongseong; Lim, Kyoung Soo; Yu, Kyung-Sang

    2015-01-01

    Background HCP1004 is a newly developed fixed-dose combination of naproxen (500 mg) and esomeprazole strontium (20 mg) that is used in the treatment of rheumatic diseases and can reduce the risk of nonsteroidal anti-inflammatory drug-associated ulcers. The aim of this study was to evaluate the pharmacokinetics (PK) and safety of HCP1004 compared to VIMOVO® (a marketed fixed-dose combination of naproxen and esomeprazole magnesium). Subjects and methods An open-label, randomized, two-treatment, two-sequence crossover, single-dose clinical study was conducted in 70 healthy volunteers. In each period, a reference (VIMOVO®) or test (HCP1004) drug was administered orally, and serial blood samples for PK analysis were collected up to 72 hours after dosing. To evaluate the PK profiles, the maximum plasma concentration (Cmax) and the area under the concentration–time curve from 0 to the last measurable time (AUC0−t) were estimated using a noncompartmental method. Safety profiles were evaluated throughout the study. Results Sixty-six of the 70 subjects completed the study. The Cmax (mean ± standard deviation) and AUC0−t (mean ± standard deviation) for naproxen in HCP1004 were 61.67±15.16 µg/mL and 1,206.52±166.46 h·µg/mL, respectively; in VIMOVO®; these values were 61.85±14.54 µg/mL and 1,211.44±170.01 h·µg/mL, respectively. The Cmax and AUC0−t for esomeprazole in HCP1004 were 658.21±510.91 ng/mL and 1,109.11±1,111.59 h·ng/mL, respectively; for VIMOVO®, these values were 595.09±364.23 ng/mL and 1,015.12±952.98 h·ng/mL, respectively. The geometric mean ratios and 90% confidence intervals (CIs) (HCP1004 to VIMOVO®) of the Cmax and AUC0−t of naproxen were 0.99 (0.94–1.06) and 1.00 (0.98–1.01), respectively. For esomeprazole, the geometric mean ratios (90% CI) for the Cmax and AUC0−t were 0.99 (0.82–1.18) and 1.04 (0.91–1.18), respectively. The overall results of the safety assessment showed no clinically significant issues for either

  14. Comparison of the pharmacokinetics and tolerability of HCP1004 (a fixed-dose combination of naproxen and esomeprazole strontium) and VIMOVO® (a marketed fixed-dose combination of naproxen and esomeprazole magnesium) in healthy volunteers.

    PubMed

    Choi, YoonJung; Han, HyeKyung; Shin, Dongseong; Lim, Kyoung Soo; Yu, Kyung-Sang

    2015-01-01

    HCP1004 is a newly developed fixed-dose combination of naproxen (500 mg) and esomeprazole strontium (20 mg) that is used in the treatment of rheumatic diseases and can reduce the risk of nonsteroidal anti-inflammatory drug-associated ulcers. The aim of this study was to evaluate the pharmacokinetics (PK) and safety of HCP1004 compared to VIMOVO(®) (a marketed fixed-dose combination of naproxen and esomeprazole magnesium). An open-label, randomized, two-treatment, two-sequence crossover, single-dose clinical study was conducted in 70 healthy volunteers. In each period, a reference (VIMOVO(®)) or test (HCP1004) drug was administered orally, and serial blood samples for PK analysis were collected up to 72 hours after dosing. To evaluate the PK profiles, the maximum plasma concentration (Cmax) and the area under the concentration-time curve from 0 to the last measurable time (AUC0-t) were estimated using a noncompartmental method. Safety profiles were evaluated throughout the study. Sixty-six of the 70 subjects completed the study. The Cmax (mean ± standard deviation) and AUC0-t (mean ± standard deviation) for naproxen in HCP1004 were 61.67 ± 15.16 µg/mL and 1,206.52 ± 166.46 h · µg/mL, respectively; in VIMOVO(®); these values were 61.85 ± 14.54 µg/mL and 1,211.44 ± 170.01 h · µg/mL, respectively. The Cmax and AUC0-t for esomeprazole in HCP1004 were 658.21 ± 510.91 ng/mL and 1,109.11 ± 1,111.59 h · ng/mL, respectively; for VIMOVO(®), these values were 595.09 ± 364.23 ng/mL and 1,015.12 ± 952.98 h · ng/mL, respectively. The geometric mean ratios and 90% confidence intervals (CIs) (HCP1004 to VIMOVO(®)) of the Cmax and AUC0-t of naproxen were 0.99 (0.94-1.06) and 1.00 (0.98-1.01), respectively. For esomeprazole, the geometric mean ratios (90% CI) for the Cmax and AUC0-t were 0.99 (0.82-1.18) and 1.04 (0.91-1.18), respectively. The overall results of the safety assessment showed no clinically significant issues for either treatment. The PK of HCP

  15. Impact of a grout curtain on groundwater regime in karst: the example of the Ðale reservoir (Croatia)

    NASA Astrophysics Data System (ADS)

    Bonacci, Ognjen; Roje-Bonacci, Tanja

    2010-05-01

    Construction of grout curtains in karst terrains is primarily connected with dams and reservoirs. Their role is to increase watertightness and prevent progressive erosion. In this presentation hourly continuous measurement of groundwater level in two deep piezometers near the Đale reservoir is analysed. The Đale reservoir in the Cetina River began operation in 1989. The total length of the grout curtain is 3.9 km. It spreads 120 m bellow the Đale dam. First analysed piezometer A is drilled in the interior part of the system, between the reservoir and the grout curtain, while the second one B is located in its external part. Distance between them is 200 m. In natural conditions, prior the grout curtain construction, groundwater level fluctuation in both of them was similar (practically the same). Construction of the grout curtain extremely changed groundwater behaviour in each of them. During the six month of continuous monitoring, differences between groundwater levels in them range between +19.86 m (groundwater in B is lower than in A) and -12.77 m (groundwater in A is lower than in B). During the 77% of analysed period the groundwater level in interior piezometer A is higher than the groundwater level in external piezometer B. In other 23% of analysed period the groundwater level in outside piezometer B is higher than in inside A. The construction of the grout curtain caused unnaturally high hydrostatic gradients, which can accelerate the dissolutional expansion of karst fractures. As a result, unbearable leakage of the reservoir Đale can occur over its lifetime. Careful analyses of groundwater level behaviour discover some other very important characteristics of karst underground morphology.

  16. Application of quality by design (QbD) to formulation and processing of naproxen pellets by extrusion-spheronization.

    PubMed

    Wang, Junlin; Kan, Shuling; Chen, Tong; Liu, Jianping

    2015-03-01

    The aim of this research was to apply quality by design (QbD) to the development of naproxen loaded core pellets which can be used as the potential core for colon-specific pellets. In the early stages of this study, prior knowledge and preliminary studies were systematically incorporated into the risk assessment using failure mode and effect analysis (FMEA) and fishbone diagram. Then Plackett-Burman design was used to screen eight potential high risk factors (spheronization speed, spheronization time, extrusion speed, drying method, CCMC-Na concentration, lactose concentration, water concentration and Tween 80 concentration) obtained from the above risk assessment. It was discovered that out of the eight potential high risk factors only three factors (spheronization speed, extrusion speed and CCMC-Na concentration) had significant effects on the quality of the pellets. This allowed the use of Box-Behnken design (BBD) to fully elucidate the relationship between the variables and critical quality attribute (CQA). Finally, the final control space was established within which the quality of the pellets can meet the requirement of colon-specific drug delivery system. This study demonstrated that naproxen loaded core pellets were successfully designed using QbD principle.

  17. Detecting social-cognitive deficits after traumatic brain injury: An ALE meta-analysis of fMRI studies.

    PubMed

    Xiao, Hui; Jacobsen, Andre; Chen, Ziqian; Wang, Yang

    2017-01-01

    Traumatic brain injury (TBI) can result in significant social dysfunction, which is represented by impairment to social-cognitive abilities (i.e. social cognition, social attention/executive function and communication). This study is aimed to explore brain networks mediating the social dysfunction after TBI and its underlying mechanisms. We performed a quantitative meta-analysis using the activation likelihood estimation (ALE) approach on functional magnetic resonance imaging (fMRI) studies of social-cognitive abilities following TBI. Sixteen studies fulfilled the inclusion criteria resulting in a total of 190 patients with TBI and 206 controls enrolled in the ALE meta-analysis. The temporoparietal junction (TPJ) and the medial prefrontal cortex (mPFC) were the specific regions that social cognition predominantly engaged. The cingulate gyrus, frontal gyrus and inferior parietal lobule were the main regions related to social attention/executive functions. Communication dysfunction, especially related to language deficits, was found to show greater activation of the temporal gyrus and fusiform gyrus in TBI. The current ALE meta-analytic findings provide evidence that patients have significant social-cognitive disabilities following TBI. The relatively limited pool of literature and the varied fMRI results from published studies indicate that social-cognitive abilities following TBI is an area that would greatly benefit from further investigation.

  18. Two Double-Blind, Multicenter, Randomized, Placebo-Controlled, Single-Dose Studies of Sumatriptan/Naproxen Sodium in the Acute Treatment of Migraine: Function, Productivity, and Satisfaction Outcomes

    PubMed Central

    Landy, Stephen; DeRossett, Sarah E.; Rapoport, Alan; Rothrock, John; Ames, Michael H.; McDonald, Susan A.; Burch, Steven P.

    2007-01-01

    Objective To describe return to normal function, productivity, and satisfaction of patients with moderate or severe migraine attacks treated with combined sumatriptan/naproxen sodium, sumatriptan alone, naproxen sodium alone, or placebo. Patients, design, and setting Patients in 2 identical, US, phase 3, randomized, double-blind, parallel-group, placebo-controlled, single-dose, multicenter studies treated a single moderate or severe migraine attack with sumatriptan/naproxen sodium (85 mg sumatriptan formulated with RT Technology and 500 mg naproxen sodium in a single-tablet formulation), sumatriptan, naproxen sodium, or placebo. Main outcome measures Ability to function (not impaired, mildly impaired, severely impaired, or required bed rest) was collected in diary cards completed immediately prior to treatment, every 30 minutes for the first 2 hours, and hourly from 2 to 24 hours while awake. Patients completed the Productivity Assessment Questionnaire (PAQ) 24 hours after study drug administration. The Patient Perception of Migraine Questionnaire (PPMQ) was administered at screening and 24 hours post treatment to capture patient satisfaction. Results Compared with the other groups, the sumatriptan/naproxen sodium group reported significantly higher levels of normal or mildly impaired functioning as early as 2 and 4 hours after dosing. They also demonstrated greater reductions in workplace productivity loss compared with placebo in both studies, and were consistently more satisfied with their treatment compared with patients in other treatment groups and compared with their usual medications. Conclusions Treatment with sumatriptan/naproxen sodium allowed significantly more subjects to return to normal or mildly impaired functioning more quickly, and sumatriptan/naproxen sodium patients were significantly more satisfied with their treatment compared with other treatment groups. Overall productivity loss was significantly reduced following use of sumatriptan/naproxen

  19. Determination of ibuprofen, naproxen and diclofenac in aqueous samples using a multi-template molecularly imprinted polymer as selective adsorbent for solid-phase extraction.

    PubMed

    Madikizela, Lawrence Mzukisi; Chimuka, Luke

    2016-09-05

    This study describes the application of multi-template molecularly imprinted polymer (MIP) as selective sorbent in the solid-phase extraction (SPE) of naproxen, ibuprofen and diclofenac from wastewater and river water. MIP was synthesized at 70°C by employing naproxen, ibuprofen and diclofenac as multi-templates, ethylene glycol dimethacrylate, 2-vinyl pyridine and toluene as cross-linker, functional monomer and porogen, respectively. Wastewater and river water samples (pH 2.5) were percolated through SPE cartridge packed with 50mg of the MIP. The cartridge was washed with 2mL of methanol-water 10:90% (v:v) prior to elution with 2mL of acetic acid-acetonitrile 20:80% (v:v). Quantification of eluted compounds was performed with high performance liquid chromatography equipped with photo diode array detection. The detection limits were 0.15, 1.00 and 0.63μgL(-1) for naproxen, ibuprofen and diclofenac, respectively. Recoveries for naproxen, ibuprofen and diclofenac in deionized water spiked at 5 and 50μgL(-1) were greater than 80%. Ibuprofen was the most frequently detected compound with maximum concentrations of 221, 67.9 and 11.4μgL(-1) in wastewater influent, effluent and river water, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Effects of the non-steroidal anti-inflammatory drug(NSAID) naproxen on gene expression of antioxidant enzymes in zebrafish (Danio rerio).

    PubMed

    Stancová, V; Ziková, A; Svobodová, Z; Kloas, W

    2015-09-01

    The aim of this study was to investigate the effects of naproxen on the gene expression of antioxidant enzymes in adult zebrafish. Surprisingly, after 2 weeks exposure no significant effect on the mRNA expression of the target genes was found in the liver. However, mRNA levels of three genes were altered significantly in the intestine. The expression of Ucp-2 decreased at the environmental concentration of 1μg/L while mRNA expression of GST p2 increased at the concentration of 100μg/L. The mRNA level for the antioxidant enzyme CAT was up-regulated significantly at both the concentrations used. Exposure to naproxen caused only moderate effects on the expression of antioxidant genes in the intestine rather than in the liver, which demonstrates that the intestine is more sensitive to waterborne naproxen exposure than the liver. Interestingly, the adverse side effects of NSAIDs occur in the gastrointestinal tract of humans. To our knowledge, this is the first study that has focused on transcriptional effects of naproxen on zebrafish. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Efficacy of naproxen with or without esomeprazole for pain and inflammation in patients after bilateral third molar extractions: A double blinded crossover study.

    PubMed

    Weckwerth, G-M; Simoneti, L-F; Zupelari-Gonçalves, P; Calvo, A-M; Brozoski, D-T; Dionísio, T-J; Torres, E-A; Lauris, J-R-P; Faria, F-A-C; Santos, C-F

    2017-01-01

    Using a double-blinded randomized crossover design, this study aimed to evaluate acute postoperative pain management, swelling and trismus in 46 volunteers undergoing extractions of the two lower third molars, in similar positions, at two different appointments who consumed a tablet of either NE (naproxen 500 mg + esomepraz ole 20 mg) or only naproxen (500 mg) every 12 hours for 4 days. Parameters were analyzed: self-reported pain intensity using a visual analog scale (VAS) pre- and postoperative mouth opening; incidence, type and severity of adverse reactions; total quantity consumed of rescue medication; and pre- and postoperative swelling. Female volunteers reported significantly more postoperative pain at 1, 1.5, 2, 3 and 4hrs after surgery while also taking their first rescue medication at a time significantly earlier when consuming NE when compared to naproxen (3.7hrs and 6.7hrs). Conversely, no differences were found between each drug group in males. In conclusion, throughout the entire study, pain was mild after using either drug in both men and women with pain scores on average well below 40mm (VAS), although in women naproxen improved acute postoperative pain management when compared to NE.

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

    PubMed

    Fernandes, M T; Vaez, S C; Lima, C M; Nahsan, F P; Loguércio, A D; Faria-E-Silva, A L

    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.

  3. Drawing and writing: An ALE meta-analysis of sensorimotor activations.

    PubMed

    Yuan, Ye; Brown, Steven

    2015-08-01

    Drawing and writing are the two major means of creating what are referred to as "images", namely visual patterns on flat surfaces. They share many sensorimotor processes related to visual guidance of hand movement, resulting in the formation of visual shapes associated with pictures and words. However, while the human capacity to draw is tens of thousands of years old, the capacity for writing is only a few thousand years old, and widespread literacy is quite recent. In order to compare the neural activations for drawing and writing, we conducted two activation likelihood estimation (ALE) meta-analyses for these two bodies of neuroimaging literature. The results showed strong overlap in the activation profiles, especially in motor areas (motor cortex, frontal eye fields, supplementary motor area, cerebellum, putamen) and several parts of the posterior parietal cortex. A distinction was found in the left posterior parietal cortex, with drawing showing a preference for a ventral region and writing a dorsal region. These results demonstrate that drawing and writing employ the same basic sensorimotor networks but that some differences exist in parietal areas involved in spatial processing. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Brewhouse-Resident Microbiota Are Responsible for Multi-Stage Fermentation of American Coolship Ale

    PubMed Central

    Bokulich, Nicholas A.; Bamforth, Charles W.; Mills, David A.

    2012-01-01

    American coolship ale (ACA) is a type of spontaneously fermented beer that employs production methods similar to traditional Belgian lambic. In spite of its growing popularity in the American craft-brewing sector, the fermentation microbiology of ACA has not been previously described, and thus the interface between production methodology and microbial community structure is unexplored. Using terminal restriction fragment length polymorphism (TRFLP), barcoded amplicon sequencing (BAS), quantitative PCR (qPCR) and culture-dependent analysis, ACA fermentations were shown to follow a consistent fermentation progression, initially dominated by Enterobacteriaceae and a range of oxidative yeasts in the first month, then ceding to Saccharomyces spp. and Lactobacillales for the following year. After one year of fermentation, Brettanomyces bruxellensis was the dominant yeast population (occasionally accompanied by minor populations of Candida spp., Pichia spp., and other yeasts) and Lactobacillales remained dominant, though various aerobic bacteria became more prevalent. This work demonstrates that ACA exhibits a conserved core microbial succession in absence of inoculation, supporting the role of a resident brewhouse microbiota. These findings establish this core microbial profile of spontaneous beer fermentations as a target for production control points and quality standards for these beers. PMID:22530036

  5. The neural basis of audiomotor entrainment: an ALE meta-analysis

    PubMed Central

    Chauvigné, Léa A. S.; Gitau, Kevin M.; Brown, Steven

    2014-01-01

    Synchronization of body movement to an acoustic rhythm is a major form of entrainment, such as occurs in dance. This is exemplified in experimental studies of finger tapping. Entrainment to a beat is contrasted with movement that is internally driven and is therefore self-paced. In order to examine brain areas important for entrainment to an acoustic beat, we meta-analyzed the functional neuroimaging literature on finger tapping (43 studies) using activation likelihood estimation (ALE) meta-analysis with a focus on the contrast between externally-paced and self-paced tapping. The results demonstrated a dissociation between two subcortical systems involved in timing, namely the cerebellum and the basal ganglia. Externally-paced tapping highlighted the importance of the spinocerebellum, most especially the vermis, which was not activated at all by self-paced tapping. In contrast, the basal ganglia, including the putamen and globus pallidus, were active during both types of tapping, but preferentially during self-paced tapping. These results suggest a central role for the spinocerebellum in audiomotor entrainment. We conclude with a theoretical discussion about the various forms of entrainment in humans and other animals. PMID:25324765

  6. Prospects for utilization of air liquefaction and enrichment system (ALES) propulsion in fully reusable launch vehicles

    NASA Technical Reports Server (NTRS)

    Bond, W. H.; Yi, A. C.

    1993-01-01

    A concept is shown for a fully reusable, earth to orbit launch vehicle with horizontal takeoff and landing, employing an air-turborocket for low speed and a rocket for high speed acceleration, both using LH2 fuel. The turborocket employs a modified liquid air cycle to supply the oxidizer. The rocket uses 90 percent pure LOX that is collected from the atmosphere, separated, and stored during operation of the turborocket from about Mach 2 to Mach 5 or 6. The takeoff weight and the thrust required at takeoff are markedly reduced by collecting the rocket oxidizer in-flight. The paper shows an approach and the corresponding technology needs for using ALES propulsion in a SSTO vehicle. Reducing the trajectory altitude at the end of collection reduces the wing area and increases payload. The use of state-of-the-art materials, such as graphite polyimide, is critical to meet the structure weight objective for SSTO. Configurations that utilize 'waverider' aerodynamics show great promise to reduce the vehicle weight.

  7. Brewhouse-resident microbiota are responsible for multi-stage fermentation of American coolship ale.

    PubMed

    Bokulich, Nicholas A; Bamforth, Charles W; Mills, David A

    2012-01-01

    American coolship ale (ACA) is a type of spontaneously fermented beer that employs production methods similar to traditional Belgian lambic. In spite of its growing popularity in the American craft-brewing sector, the fermentation microbiology of ACA has not been previously described, and thus the interface between production methodology and microbial community structure is unexplored. Using terminal restriction fragment length polymorphism (TRFLP), barcoded amplicon sequencing (BAS), quantitative PCR (qPCR) and culture-dependent analysis, ACA fermentations were shown to follow a consistent fermentation progression, initially dominated by Enterobacteriaceae and a range of oxidative yeasts in the first month, then ceding to Saccharomyces spp. and Lactobacillales for the following year. After one year of fermentation, Brettanomyces bruxellensis was the dominant yeast population (occasionally accompanied by minor populations of Candida spp., Pichia spp., and other yeasts) and Lactobacillales remained dominant, though various aerobic bacteria became more prevalent. This work demonstrates that ACA exhibits a conserved core microbial succession in absence of inoculation, supporting the role of a resident brewhouse microbiota. These findings establish this core microbial profile of spontaneous beer fermentations as a target for production control points and quality standards for these beers.

  8. Spent Fuel Ratio Estimates from Numerical Models in ALE3D

    SciTech Connect

    Margraf, J. D.; Dunn, T. A.

    Potential threat of intentional sabotage of spent nuclear fuel storage facilities is of significant importance to national security. Paramount is the study of focused energy attacks on these materials and the potential release of aerosolized hazardous particulates into the environment. Depleted uranium oxide (DUO 2) is often chosen as a surrogate material for testing due to the unreasonable cost and safety demands for conducting full-scale tests with real spent nuclear fuel. To account for differences in mechanical response resulting in changes to particle distribution it is necessary to scale the DUO 2 results to get a proper measure for spentmore » fuel. This is accomplished with the spent fuel ratio (SFR), the ratio of respirable aerosol mass released due to identical damage conditions between a spent fuel and a surrogate material like depleted uranium oxide (DUO 2). A very limited number of full-scale experiments have been carried out to capture this data, and the oft-questioned validity of the results typically leads to overly-conservative risk estimates. In the present work, the ALE3D hydrocode is used to simulate DUO 2 and spent nuclear fuel pellets impacted by metal jets. The results demonstrate an alternative approach to estimate the respirable release fraction of fragmented nuclear fuel.« less

  9. Natural hazards in the karst areas of the Viñales National Park, Cuba

    NASA Astrophysics Data System (ADS)

    Govea Blanco, Darlenys; Farfan Gonzalez, Hermes; Dias Guanche, Carlos; Parise, Mario; Ramirez, Robert

    2010-05-01

    Cuban karst is subject to several natural hazards, the great majority of which is hydro-meteorological in character: intense rainstorms, tropical cyclones, seawater inundation, etc. A further, serious problem is represented by droughts, that have become very severe during the recent years, due to longer persistence of the dry season. Beside these hazards, seismic shocks in the eastern part of the country, and mass movements in the mountain areas have also to be mentioned. In general, it has to be noted that both casualties and economic losses from natural disasters have slowly decreased during the last decades at Cuba. Viñales National Park, as many other natural landforms in the Cuban karst, has a great potential for development and exploitation in several different fields, from agriculture, to tourism and recreational activities. At these aims, it is necessary to preserve the natural landscape, its beauty and resources, and, at the same time, improve the quality of people living in these environments. In particular, to face the social changes at present occurring in the area is one of the most difficult task for those people that are in charge of land management and development. It has also to be remembered that "Valle de Viñales" has been included by UNESCO in the World Cultural Heritage List. The main scenarios of natural hazards in the Viñales National Park are described in this contribution, and analyzed by means of different methodologies. Flooded areas have been mapped in the field soon after the occurrence of an extreme event as the hurricane Ike, characterized by rainfall higher than 300 mm/day, and preceded only ten days before by hurricane Gustav, that discharged in the area an amount of 120 mm/day of rain. As a consequence of the temporal vicinity of the two events, the terranes were already highly saturated at the time of occurrence of hurricane Ike, which thus resulted to be one of the most extreme floods ever recorded in the area. Electrostatic

  10. Double-Track Electrochemical Green Approach for Simultaneous Dissolution Profiling of Naproxen Sodium and Diphenhydramine Hydrochloride.

    PubMed

    Shehata, Mostafa A; Fawaz, Esraa M; El-Rahman, Mohamed K Abd; Abdel-Moety, Ezzat M

    2017-11-30

    Acquisition of the dissolution profiles of more than single active ingredient in a multi-analyte pharmaceutical formulation is a mandatory manufacturing practice that is dominated by utilization of the off-line separation-based chromatographic methods. This contribution adopts a new "Double-Track" approach with the ultimate goal of advancing the in-line potentiometric sensors to their most effective applicability for simultaneous acquisition of the dissolution profiles of two active ingredients in a binary pharmaceutical formulation. The unique abilities of these sensors for real-time measurements is the key driver for adoption of "green analytical chemistry" (GAC) principles aiming to expand the application of eco-friendly analytical methods With the aim of performing a side-by-side comparison, this work investigates the degree of adherence of ISEs to the 12 principles of GAC in multicomponent dissolution profiling with respect to the HPLC. For the proof of concept, a binary mixture of naproxen sodium (NAPR) and diphenhydramine hydrochloride (DIPH) marketed as Aleve pm ® tablets was selected as a model for which dissolution profiles were attained by two techniques. The first "Double-Track" in-line strategy depends on dipping two highly integrated membrane sensors for continuous monitoring of the dissolution of each active pharmaceutical ingredient (API) by tracing the e.m.f change over the time scale. For the determination of NAPR, sensor I was developed using tridodecyl methyl ammonium chloride as an anion exchanger, while sensor II was developed for the determination of DIPH using potassium tetrakis (4-chlorophenyl) borate as a cation exchanger. The second off-line strategy utilizes a separation-based HPLC method via off-line tracking the increase of peak area by UV detection at 220nm over time using a mobile phase of acetonitrile: water (90:10) pH 3. The advantages of the newly introduced "Double-Track" approach regarding GAC principles are highlighted, and

  11. Sorption, Photodegradation, and Chemical Transformation of Naproxen and Ibuprofen in Soils and Water

    NASA Astrophysics Data System (ADS)

    Vulava, V. M.; Cory, W. C.; Murphey, V.; Ulmer, C.

    2015-12-01

    Trace levels of pharmaceutically active compounds (PhACs) are increasingly being found in municipal drinking water and natural streams around the world. PhACs enter natural water systems after passing through wastewater treatment plants that have proven to be relatively inefficient at removing them. Once they are released into the environment, they can undergo (1) soil sorption, (2) photodegradation, and/or (3) chemical transformation into structurally similar compounds. The overarching goal of this study is to understand the geochemical fate of common PhACs in the environment. Here we report on our studies with naproxen (NAP) and ibuprofen (IBP) in soils and water. Both compounds are complex nonpolar (aromatic) organic molecules with polar (carboxylic acid) functional groups. The carboxylic functional groups are likely to be deprotonated at environmentally relevant pHs (~4-8). Sorption studies of both compounds were conducted in clean and relatively acidic (soil pH ~4.5-6.5) natural soils that contained varying levels of organic matter (OM), clay minerals, and Fe oxides. OM was observed to play an important role in each of the above three processes. Sorption was observed to be stronger and nonlinear in higher OM soils, while weaker but still significant in lower OM, higher clay soils; the amphiphilic nature of NAP and IBP combined with the complex charged and nonpolar surfaces available in the soil was observed to control the sorption behavior. Both NAP and IBP underwent rapid photodegradation in aqueous suspensions when exposed to simulated sunlight. The degradation rates were observed to change in the presence of humic acid or fulvic acid. During sorption and photodegradation experiments, common transformation products were observed for both NAP and IBP. The transformation products produced were indicative of chemical transformation and not biological factors. Concentrations of the transformation products were significantly higher in the photoexposed aqueous

  12. Relating hydrogen-bonding interactions with the phase behavior of naproxen/PVP K 25 solid dispersions: evaluation of solution-cast and quench-cooled films.

    PubMed

    Paudel, Amrit; Nies, Erik; Van den Mooter, Guy

    2012-11-05

    In this work, we investigated the relationship between various intermolecular hydrogen-bonding (H-bonding) interactions and the miscibility of the model hydrophobic drug naproxen with the hydrophilic polymer polyvinylpyrrolidone (PVP) across an entire composition range of solid dispersions prepared by quasi-equilibrium film casting and nonequilibrium melt quench cooling. The binary phase behavior in solid dispersions exhibited substantial processing method dependence. The solid state solubility of crystalline naproxen in PVP to form amorphous solid dispersions was 35% and 70% w/w naproxen in solution-cast films and quench-cooled films, respectively. However, the presence of a single mixed phase glass transition indicated the amorphous miscibility to be 20% w/w naproxen for the films, beyond which amorphous-amorphous and/or crystalline phase separations were apparent. This was further supported by the solution state interactions data such as PVP globular size distribution and solution infrared spectral profiles. The borderline melt composition showed cooling rate dependence of amorphization. The glass transition and melting point depression profiles of the system were treated with the analytical expressions based on Flory-Huggins mixing theory to interpolate the equilibrium solid solubility. FTIR analysis and subsequent spectral deconvolution revealed composition and miscibility dependent variations in the strength of drug-polymer intermolecular H-bonding. Two types of H-bonded populations were evidenced from 25% w/w and 35% w/w naproxen in solution-cast films and quench-cooled films, respectively, with the higher fraction of strongly H-bonded population in the drug rich domains of phase separated amorphous film compositions and highly drug loaded amorphous quench-cooled dispersions.

  13. Naproxen, a Nonsteroidal Anti-Inflammatory Drug, Can Affect Daily Hypobaric Hypoxia-Induced Alterations of Monoamine Levels in Different Areas of the Brain in Male Rats.

    PubMed

    Goswami, Ananda Raj; Dutta, Goutam; Ghosh, Tusharkanti

    2016-06-01

    Goswami, Ananda Raj, Goutam Dutta, and Tusharkanti Ghosh. Naproxen, a nonsteroidal anti-inflammatory drug can affect daily hypobaric hypoxia-induced alterations of monoamine levels in different areas of the brain in male rats. High Alt Med Biol. 17:133-140, 2016.-The oxidative stress (OS)-induced prostaglandin (PG) release, in hypobaric hypoxic (HHc) condition, may be linked with the changes of brain monoamines. The present study intends to explore the changes of monoamines in hypothalamus (H), cerebral cortex (CC), and cerebellum (CB) along with the motor activity in rats after exposing them to simulated hypobaric condition and the role of PGs on the daily hypobaric hypoxia (DHH)-induced alteration of brain monoamines by administering, an inhibitor of PG synthesis, naproxen. The rats were exposed to a decompression chamber at 18,000 ft for 8 hours per day for 6 days after administration of vehicle or naproxen (18 mg/kg body wt.). The monoamine levels (epinephrine, E; norepinephrine, NE; dopamine, DA; and 5-hydroxytryptamine, 5-HT) in CC, CB, and H were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, and the locomotor behavior was measured by open field test. The NE and DA levels were decreased in CC, CB, and H of the rat brain in HHc condition. The E and 5-HT levels were decreased in CC, but in H and CB, they remained unaltered in HHc condition. These DHH-induced changes of monoamines in brain areas were prevented after administration of naproxen in HHc condition. The locomotor behavior remained unaltered in HHc condition and after administration of naproxen in HHc condition. The DHH-induced changes of monoamines in the brain in HHc condition are probably linked with PGs that may be induced by OS.

  14. Correlation between in vitro and in vivo concentration–effect relationships of naproxen in rats and healthy volunteers

    PubMed Central

    Huntjens, Dymphy R H; Spalding, David J M; Danhof, Meindert; Della Pasqua, Oscar E

    2006-01-01

    Understanding the mechanisms underlying the analgesic effect of new cyclooxygenase inhibitors is essential to identify dosing requirements in early stages of drug development. Accurate extrapolation to humans of in vitro and in vivo findings in preclinical species is needed to optimise dosing regimen in inflammatory conditions. The current investigation characterises the inhibition of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) by naproxen in vitro and in vivo in rat and human blood. The inhibition of PGE2 in the absence or presence of increasing concentrations of naproxen (10−8–10−1 M) was measured by ex vivo whole blood stimulation with LPS, whereas inhibition of TXB2 was measured in serum following blood clotting. In further experiments, inhibition of PGE2 and TXB2 levels was also assessed ex vivo in animals treated with naproxen (2.5, 10, 25 mg kg−1). Subsequently, pharmacokinetic (PK)/pharmacodynamics (PD) modelling of in vitro and in vivo data was performed using nonlinear mixed effects in NONMEM (V). Inhibition of PGE2 and TXB2 was characterised by a sigmoid Emax model. The exposure–response relationships in vitro and in vivo were of the same order of magnitude in both species. IC80 estimates obtained in vitro were similar for PGE2 inhibition (130.8±11 and 131.9±19 10−6 M, mean±s.d. for humans and rats, respectively), but slightly different for TXB2 inhibition (103.9±15 and 151.4±40 10−6 M, mean±s.d. for humans and rats, respectively, P< 0.05). These differences, however, may not be biologically relevant. The results confirm the value of exposure–effect relationships determined in vitro as a means to predict the pharmacological activity in vivo. This analysis also highlights the need to parameterise concentration–effect relationships in early drug development, as indicated by the estimates of IC80 for PGE2 and TXB2 inhibition. PMID:16682968

  15. Efficacy, end points and eventualities: sumatriptan/naproxen versus butalbital/paracetamol/caffeine in the treatment of migraine.

    PubMed

    Fox, Anthony W

    2012-09-01

    Migraine is a widespread, relapsing, remittent syndrome. No animal model predicts whether test medications will be clinically useful. Using a modern, well-controlled, sophisticated study design, Derosier et al. demonstrates not only that a butalbital formulation has modest efficacy as an acute treatment for migraine but also that a sumatriptan-naproxen combination is superior. These conclusions are reached using a variety of internally consistent secondary efficacy end points. The primary end point chosen (highly conservative and fashionable in some academic circles) was a technical failure (and not a negative experimental finding). Migraine is intrinsically pleiomorphic: diverse treatment options help match patient with therapy. This study does not justify blanket bans on (admittedly hazardous) barbiturate therapies, and regulators should not impose end point conservatism to an extent that will stifle further progress.

  16. Investigation on influence of Wurster coating process parameters for the development of delayed release minitablets of Naproxen.

    PubMed

    Shah, Neha; Mehta, Tejal; Aware, Rahul; Shetty, Vasant

    2017-12-01

    The present work aims at studying process parameters affecting coating of minitablets (3 mm in diameter) through Wurster coating process. Minitablets of Naproxen with high drug loading were manufactured using 3 mm multi-tip punches. The release profile of core pellets (published) and minitablets was compared with that of marketed formulation. The core formulation of minitablets was found to show similarity in dissolution profile with marketed formulation and hence was further carried forward for functional coating over it. Wurster processing was implemented to pursue functional coating over core formulation. Different process parameters were screened and control strategy was applied for factors significantly affecting the process. Modified Plackett Burman Design was applied for studying important factors. Based on the significant factors and minimum level of coating required for functionalization, optimized process was executed. Final coated batch was evaluated for coating thickness, surface morphology, and drug release study.

  17. Determining particle size and water content by near-infrared spectroscopy in the granulation of naproxen sodium.

    PubMed

    Bär, David; Debus, Heiko; Brzenczek, Sina; Fischer, Wolfgang; Imming, Peter

    2018-03-20

    Near-infrared spectroscopy is frequently used by the pharmaceutical industry to monitor and optimize several production processes. In combination with chemometrics, a mathematical-statistical technique, the following advantages of near-infrared spectroscopy can be applied: It is a fast, non-destructive, non-invasive, and economical analytical method. One of the most advanced and popular chemometric technique is the partial least square algorithm with its best applicability in routine and its results. The required reference analytic enables the analysis of various parameters of interest, for example, moisture content, particle size, and many others. Parameters like the correlation coefficient, root mean square error of prediction, root mean square error of calibration, and root mean square error of validation have been used for evaluating the applicability and robustness of these analytical methods developed. This study deals with investigating a Naproxen Sodium granulation process using near-infrared spectroscopy and the development of water content and particle-size methods. For the water content method, one should consider a maximum water content of about 21% in the granulation process, which must be confirmed by the loss on drying. Further influences to be considered are the constantly changing product temperature, rising to about 54 °C, the creation of hydrated states of Naproxen Sodium when using a maximum of about 21% water content, and the large quantity of about 87% Naproxen Sodium in the formulation. It was considered to use a combination of these influences in developing the near-infrared spectroscopy method for the water content of Naproxen Sodium granules. The "Root Mean Square Error" was 0.25% for calibration dataset and 0.30% for the validation dataset, which was obtained after different stages of optimization by multiplicative scatter correction and the first derivative. Using laser diffraction, the granules have been analyzed for particle sizes

  18. Adsorption characteristics of selected pharmaceuticals and an endocrine disrupting compound-Naproxen, carbamazepine and nonylphenol-on activated carbon.

    PubMed

    Yu, Zirui; Peldszus, Sigrid; Huck, Peter M

    2008-06-01

    The adsorption of two representative pharmaceutically active compounds (PhACs) (naproxen and carbamazepine) and one endocrine disrupting compound (nonylphenol) were evaluated on two types of activated carbon. When determining their isotherms at environmentally relevant concentration levels, it was found that at this low concentration range (10-800 ng/L), removals of the target compounds were contrary to expectations based on their hydrophobicity. Nonylphenol (log K(ow) 5.8) was most poorly adsorbed, whereas carbamazepine (log K(ow) 2.45) was most adsorbable. Nonylphenol Freundlich isotherms at this very low concentration range had a much higher 1/n compared to isotherms at much higher concentrations. This indicates that extrapolation from an isotherm obtained at a high concentration range to predict the adsorption of nonylphenol at a concentration well below the range of the original isotherm, leads to a substantial overestimation of its removals. Comparison of isotherms for the target compounds to those for other conventional micropollutants suggested that naproxen and carbamazepine could be effectively removed by applying the same dosage utilized to remove odorous compounds (geosmin and MIB) at very low concentrations. The impact of competitive adsorption by background natural organic matter (NOM) on the adsorption of the target compounds was quantified by using the ideal adsorbed solution theory (IAST) in combination with the equivalent background compound (EBC) approach. The fulfilment of the requirements for applying the simplified IAST-EBC model, which leads to the conclusion that the percentage removal of the target compounds at a given carbon dosage is independent of the initial contaminant concentration, was confirmed for the situation examined in the paper. On this basis it is suggested that the estimated minimum carbon usage rates (CURs) to achieve 90% removal of these emerging contaminants would be valid at concentrations of less than 500 ng/L in

  19. Development and Evaluation of Naproxen Sodium Gel Using Piper cubeba for Enhanced Transdermal Drug Delivery and Therapeutic Facilitation.

    PubMed

    Patwardhan, Sunetra; Patil, Manohar; Sockalingam, Anbazhagan

    2017-01-01

    The absorption of drug through skin avoids many side effects of oral route like gastric irritation, nausea, systemic toxicity etc and thus improves patient compliance. Naproxen sodium (NPRS) is one of the potent NSAID agents. The present study was aimed to develop and evaluate the gel formulation containing NPRS for transdermal drug delivery reducing the side effects and improving patient compliance. The patents on topical delivery of NSAIDS (US 9012402 B1, US 9072659 B2, US 20150258196 A1) and patents indicating use of herbal penetration enhancers (US 20100273746A1, WO 2005009510 A2, US 6004969 A) helped in selecting the drug, excipients. Current protocol employs various extracts of Piper cubeba fruit to evaluate its role in absorption of NPRS. Various batches containing 1% NPRS and varying concentrations of synthetic permeation enhancers or the extracts were formulated in carbopol gel. Gel was evaluated for parameters like organoleptic parameters, pH, viscosity and spreadability. An ex-vivo percutaneous absorption of NPRS from gel was investigated and compared with best performing synthetic enhancer, transcutol P (TP). The batch containing 2% n-hexane extract (NHE) of Piper cubeba showed higher permeation than TP and Chloroform (CE), Methanolic (ME) and aqueous (AE) extracts as well. It showed improved % cumulative release (85.09%) and flux (278.61μg/cm2.h), as compared to TP and other extracts. Histopathology indicated the formulation safer as compared to that with synthetic enhancer. It suggests P. cubeba as effective and safer tool for transdermal delivery and acts as therapeutic facilitator for naproxen. GC-MS analysis indicates lignans & terpenes in NHE to which this permeation enhancement activity may be attributed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Characterization of Brazilian lager and brown ale beers based on color, phenolic compounds, and antioxidant activity using chemometrics.

    PubMed

    Granato, Daniel; Branco, Gabriel Favalli; Faria, José de Assis Fonseca; Cruz, Adriano Gomes

    2011-02-01

    Epidemiological studies have shown that beer has positive effects on inhibiting atherosclerosis, decreasing the content of serum low-density lipoprotein cholesterol and triglycerides, by acting as in vivo free radical scavenger. In this research, the antioxidant activity of commercial Brazilian beers (n = 29) was determined by the oxygen radical absorbance capacity (ORAC) and 1,1-diphenyl-2-picrylhydrazyl (DPPH(·) ) assays and results were analyzed by chemometrics. The brown ale samples (n = 11) presented higher (P < 0.05) flavonoids (124.01 mg L(-1) ), total phenolics (362.22 mg L(-1) ), non-flavonoid phenolics (238.21 mg L(-1) ), lightness (69.48), redness (35.75), yellowness (55.71), color intensity (66.86), hue angle (59.14), color saturation (0.9620), DPPH(·) values (30.96% inhibition), and ORAC values (3, 659.36 µmol Trolox equivalents L(-1) ), compared to lager samples (n = 18). Brown ale beers presented higher antioxidant properties (P < 0.05) measured by ORAC (1.93 times higher) and DPPH (1.65 times higher) compared to lager beer. ORAC values correlated well with the content of flavonoids (r = 0.47; P = 0.01), total phenolic compounds (r = 0.44; P < 0.01) and DPPH (r = 0.67; P < 0.01). DPPH values also correlated well to the content of flavonoids (r = 0.69; P < 0.01), total phenolic compounds (r = 0.60; P < 0.01), and non-flavonoid compounds (r = 0.46; P = 0.01). The results suggest that brown ale beers, and less significantly lager beers, could be sources of bioactive compounds with suitable free radical scavenging properties. 2010 Society of Chemical Industry.

  1. Features of the adsoprtion of naproxen on the chiral stationary phase (S,S)-Whelk-O1 under reversed-phase conditions

    SciTech Connect

    Asnin, Leonid; Gritti, Fabrice; Kaczmarski, Krzysztof

    Using elution chromatography, we studied the adsorption mechanism of the Naproxen enantiomers on the chiral stationary phase (S,S)-Whelk-O1, from buffered methanol-water solutions. We propose an adsorption mechanism that assumes monolayer adsorption of the more retained enantiomer and the associative adsorption of the less retained one. The effects of the mobile phase composition on the adsorption of Naproxen are discussed. The combination of an elevated column temperature and of the use of an acidic mobile phase led to the degradation of the column and caused a major loss of its separation ability. The use of a moderately acidic mobile phase atmore » temperature slightly above ambient did not produce rapid severe damages but, nevertheless, hampered the experiments and caused a slow gradual deterioration of the column.« less

  2. Comparison of the postoperative analgesic effects of paracetamol-codeine phosphate and naproxen sodium-codeine phosphate for lumbar disk surgery.

    PubMed

    Polat, Reyhan; Peker, Kevser; Gülöksüz, Çiğdem Topçu; Ergil, Julide; Akkaya, Taylan

    2015-09-01

    The aim of this study was to compared the efficacy of paracetamol-codeine phosphate and naproxen sodium-codeine phosphate on postoperative pain and tramadol consumption during the first 24 hours after a lumbar disk surgery. After Ethics Committee approval and informed consent had been obtained, 64 patients were allocated into three groups. Patients received oral paracetamol-codeine (300 mg + 30 mg; Group P), naproxen sodium-codeine (550 mg + 30 mg; Group N), or placebo tablets (Group C) 30 minutes prior to induction of anesthesia. Patient-controlled analgesia was supplied postoperatively using tramadol. Pain intensity, tramadol consumption, and side effects were recorded every 1 hour, 2 hours, 6 hours, 12 hours, and 24 hours after surgery. Whole study period pain intensity (visual analogue scale scores) was lower in Group P (p = 0.007) and Group N (p = 0.001), compared with Group C, however, there was no statistically significant difference between Group P and Group N regarding pain intensity (p > 0.05). Tramadol consumption was lower in Group P and Group N, compared with Group C (p < 0.001), and in turn the lowest incidence of tramadol consumption was detected in Group P compared with Group N (p < 0.001) and Group C (p < 0.001). Side effects were similar between the groups. Preemptive administration of paracetamol-codeine and naproxen sodium-codeine combination significantly reduced tramadol consumption and provided more effective analgesia compared with placebo. The paracetamol-codeine combination was superior to naproxen sodium-codeine with regard to tramadol consumption. Copyright © 2015. Published by Elsevier Taiwan.

  3. Development and validation of an LC-ESI-MS/MS method for the simultaneous quantification of naproxen and sumatriptan in human plasma: application to a pharmacokinetic study.

    PubMed

    Brêtas, Juliana Machado; César, Isabela Costa; Brêtas, Camila Machado; Teixeira, Leonardo de Souza; Bellorio, Karini Bruno; Mundim, Iram Moreira; Pianetti, Gerson Antônio

    2016-06-01

    A sensitive and fast liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the simultaneous quantification of naproxen and sumatriptan in human plasma. A simple liquid-liquid extraction procedure, with a mixture of ethyl acetate, methyl tert-butyl ether, and dichloromethane (4:3:3, v/v), was used for the cleanup of plasma. Naratriptan and aceclofenac were employed as internal standards. The analyses were carried out using an ACE C18 column (50 × 4.6 mm i.d.; particle size 5 μm) and a mobile phase consisting of 2 mM aqueous ammonium acetate with 0.025 % formic acid and methanol (38:62, v/v). A triple-quadrupole mass spectrometer equipped with an electrospray source in the positive mode was set up in the selective reaction monitoring mode to detect the ion transitions m/z 231.67 → m/z 185.07, m/z 296.70 → m/z 157.30, m/z 354.80 → m/z 215.00, and m/z 336.80 → m/z 97.94 for naproxen, sumatriptan, aceclofenac, and naratriptan, respectively. The method was validated and proved to be linear, accurate, precise, and selective over the ranges of 2.5-130 μg mL(-1) for naproxen and 1-50 ng mL(-1) for sumatriptan. The validated method was successfully applied to a pharmacokinetic study with simultaneous administration of naproxen sodium and sumatriptan succinate tablet formulations in healthy volunteers.

  4. Calibration of 3D ALE finite element model from experiments on friction stir welding of lap joints

    NASA Astrophysics Data System (ADS)

    Fourment, Lionel; Gastebois, Sabrina; Dubourg, Laurent

    2016-10-01

    In order to support the design of such a complex process like Friction Stir Welding (FSW) for the aeronautic industry, numerical simulation software requires (1) developing an efficient and accurate Finite Element (F.E.) formulation that allows predicting welding defects, (2) properly modeling the thermo-mechanical complexity of the FSW process and (3) calibrating the F.E. model from accurate measurements from FSW experiments. This work uses a parallel ALE formulation developed in the Forge® F.E. code to model the different possible defects (flashes and worm holes), while pin and shoulder threads are modeled by a new friction law at the tool / material interface. FSW experiments require using a complex tool with scroll on shoulder, which is instrumented for providing sensitive thermal data close to the joint. Calibration of unknown material thermal coefficients, constitutive equations parameters and friction model from measured forces, torques and temperatures is carried out using two F.E. models, Eulerian and ALE, to reach a satisfactory agreement assessed by the proper sensitivity of the simulation to process parameters.

  5. Grey Matter Alterations Co-Localize with Functional Abnormalities in Developmental Dyslexia: An ALE Meta-Analysis

    PubMed Central

    Linkersdörfer, Janosch; Lonnemann, Jan; Lindberg, Sven; Hasselhorn, Marcus; Fiebach, Christian J.

    2012-01-01

    The neural correlates of developmental dyslexia have been investigated intensively over the last two decades and reliable evidence for a dysfunction of left-hemispheric reading systems in dyslexic readers has been found in functional neuroimaging studies. In addition, structural imaging studies using voxel-based morphometry (VBM) demonstrated grey matter reductions in dyslexics in several brain regions. To objectively assess the consistency of these findings, we performed activation likelihood estimation (ALE) meta-analysis on nine published VBM studies reporting 62 foci of grey matter reduction in dyslexic readers. We found six significant clusters of convergence in bilateral temporo-parietal and left occipito-temporal cortical regions and in the cerebellum bilaterally. To identify possible overlaps between structural and functional deviations in dyslexic readers, we conducted additional ALE meta-analyses of imaging studies reporting functional underactivations (125 foci from 24 studies) or overactivations (95 foci from 11 studies ) in dyslexics. Subsequent conjunction analyses revealed overlaps between the results of the VBM meta-analysis and the meta-analysis of functional underactivations in the fusiform and supramarginal gyri of the left hemisphere. An overlap between VBM results and the meta-analysis of functional overactivations was found in the left cerebellum. The results of our study provide evidence for consistent grey matter variations bilaterally in the dyslexic brain and substantial overlap of these structural variations with functional abnormalities in left hemispheric regions. PMID:22916214

  6. Cerium-doped -Ni(OH)2 hexagon nanosheets: an effective photocatalyst for degradation of the emerging water pollutant naproxen.

    PubMed

    Regmi, Chhabilal; Maya-Flores, Etel; Lee, Soo Wohn; Rodríguez-González, Vicente

    2018-06-21

    Nickel hydroxide β-Ni(OH)2 hexagonal nanosheets were synthetized via a hydrothermal exfoliation process. The practical microwave assisted hydrothermal method facilitated obtain layered nickel 3D nanoplates with cerium functionalization in 5h. The as-produced nanostructures were characterized by XRD, XPS, FESEM, FT-IR, PL, UV-vis, and BET techniques. The hydroxilated structures are nano-thick hexagonal plates having sides with 28 nm in length and 5 nm of average thickness. UV and PL irradiation was used to study the photoactive properties in the degradation of a pharmaceutical emerging pollutant, naproxen. UV-vis spectroscopy and high-performance liquid chromatography (HPLC) monitoring indicated that the Ni(OH)2-Ce nanostructures are an effective photocatalyst for naproxen degradation including 40 % of mineralization of this highly recalcitrant drug. The photocatalyst showed stability for two consecutive cycles, preserving its photoactive and structural characteristics. Ce3+ doped nanoplates and surface functionalized Ce4+ act as charge separators and scavenging agents for the enhanced photodegradation of naproxen. © 2018 IOP Publishing Ltd.

  7. Occurrence of naproxen, ibuprofen, and diclofenac residues in wastewater and river water of KwaZulu-Natal Province in South Africa.

    PubMed

    Madikizela, Lawrence Mzukisi; Chimuka, Luke

    2017-07-01

    The present paper reports a detailed study that is based on the monitoring of naproxen, ibuprofen, and diclofenac in Mbokodweni River and wastewater treatment plants (WWTPs) located around the city of Durban in KwaZulu-Natal Province of South Africa. Target compounds were extracted from water samples using a multi-template molecularly imprinted solid-phase extraction prior to separation and quantification on a high-performance liquid chromatography equipped with photo diode array detector. The analytical method yielded the detection limits of 0.15, 1.00, and 0.63 μg/L for naproxen, ibuprofen, and diclofenac, respectively. Solid-phase extraction method was evaluated for its performance using deionized water samples that were spiked with 5 and 50 μg/L of target compounds. Recoveries were greater than 80% for all target compounds with RSD values in the range of 4.1 to 10%. Target compounds were detected in most wastewater and river water samples with ibuprofen being the most frequently detected pharmaceutical. Maximum concentrations detected in river water for naproxen, ibuprofen, and diclofenac were 6.84, 19.2, and 9.69 μg/L, respectively. The concentrations of target compounds found in effluent and river water samples compared well with some studies. The analytical method employed in this work is fast, selective, sensitive, and affordable; therefore, it can be used routinely to evaluate the occurrence of acidic pharmaceuticals in South African water resources.

  8. Vortex-assisted surfactant-enhanced emulsification microextraction based on solidification of floating organic drop combined with high performance liquid chromatography for determination of naproxen and nabumetone.

    PubMed

    Asadi, Mohammad; Haji Shabani, Ali Mohammad; Dadfarnia, Shayessteh; Abbasi, Bijan

    2015-12-18

    A novel, rapid, simple and green vortex-assisted surfactant-enhanced emulsification microextraction method based on solidification of floating organic drop was developed for simultaneous separation/preconcentration and determination of ultra trace amounts of naproxen and nabumetone with high performance liquid chromatography-fluorescence detection. Some parameters influencing the extraction efficiency of analytes such as type and volume of extractant, type and concentration of surfactant, sample pH, KCl concentration, sample volume, and vortex time were investigated and optimized. Under optimal conditions, the calibration graph exhibited linearity in the range of 3.0-300.0ngL(-1) for naproxen and 7.0-300.0ngL(-1) for nabumetone with a good coefficient of determination (R(2)>0.999). The limits of detection were 0.9 and 2.1ngL(-1). The relative standard deviations for inter- and intra-day assays were in the range of 5.8-10.1% and 3.8-6.1%, respectively. The method was applied to the determination of naproxen and nabumetone in urine, water, wastewater and milk samples and the accuracy was evaluated through recovery experiments. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. An efficient approach to selective electromembrane extraction of naproxen by means of molecularly imprinted polymer-coated multi-walled carbon nanotubes-reinforced hollow fibers.

    PubMed

    Tahmasebi, Zeinab; Davarani, Saied Saeed Hosseiny; Asgharinezhad, Ali Akbar

    2016-10-28

    In this work, a novel microextraction technique using molecularly imprinted polymer-coated multi-walled carbon nanotubes (MIP-MWCNTs) in electromembrane extraction (EME) procedure is described. The method in combination with HPLC-UV was utilized to determine naproxen, as an acidic model drug, in urine, plasma and wastewater samples. For this purpose, MIP-MWCNTs were placed in the pores of polypropylene hollow fiber. The MIP-MWCNTs-EME method has the advantages of high selectivity and cleanup of MIP along with high enrichment ability of the EME in a single step extraction. Continuing with the research, optimization of the factors affecting the migration of naproxen from sample solutions to MIP-MWCNTs sites and then into the lumen of hollow fiber was explored. Under the optimized conditions, the limit of detection (LOD) of the developed method was calculated to be 0.3μgL -1 . All relative standard deviations (RSDs) were lower than 3%. Linearity of the method was obtained within the range of 1-1000μgL -1 with the coefficient of determination (r 2 ) being higher than 0.999. Under the optimized conditions, an extraction recovery of 66% was obtained, which corresponded to a preconcentration factor of 88. Finally, the developed method was satisfactorily used to determine naproxen in urine, plasma and wastewater samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Gas-driven lava lake fluctuations at Erta 'Ale volcano (Ethiopia) revealed by MODIS measurements

    NASA Astrophysics Data System (ADS)

    Vergniolle, Sylvie; Bouche, Emmanuella

    2016-09-01

    The long-lived lava lake of Erta 'Ale volcano (Ethiopia) is remotely monitored by moderate resolution imaging spectroradiometers (MODIS) installed on satellites. The Normalised Thermal Index (NTI) (Wright et al. Remote Sens Environ 82:135-155 2002) is shown to be proportional to the volume of the lava lake based on visual observations. The lava lake's variable level can be plausibly related to a stable foam, i.e. a mixture composed of densely packed non-coalescing bubbles in suspension within a liquid. This foam is trapped at the top of the magma reservoir, and its thickness changes in response to the gas flux feeding the foam being successively turned on and off. The temporal evolution of the foam thickness, and the resulting variation of the volume of the lava lake, is calculated numerically by assuming that the gas flux feeding the foam, initially constant and homogeneous since December 9, 2002, is suddenly stopped on December 13, 2002 and not restarted before May 2003. The best fit between the theoretical foam thickness and the level of the lava lake deduced from the NTI provides an estimate of both the reservoir radius, 155-170 m, and the gas flux feeding the foam, 5.5×10-3-7.2×10-3 m 3 s -1 when existing. This is in agreement with previous estimates from acoustic measurements (Bouche et al. Earth Planet Sci Lett 295:37-48 2010). The very good agreement between the theoretical foam thickness and that deduced from MODIS data shows for the first time the existence of a regime based on the behaviour of a stable foam, whose spreading towards the conduit ("wide" conduit condition), can explain the long-lived activity. Our predictive model, which links the gas flux at the vent to the foam spreading, could potentially be used on any volcano with a long-lived activity. The underlying gas flux and the horizontal surface area of the magma reservoir can then be deduced by combining modelling to continuous measurements of gas flux. The lava lake, when high, often shows

  11. Model-based analysis of thromboxane B{sub 2} and prostaglandin E{sub 2} as biomarkers in the safety evaluation of naproxen

    SciTech Connect

    Sahota, Tarjinder; Sanderson, Ian; Danhof, Meindert

    The assessment of safety in traditional toxicology protocols relies on evidence arising from observed adverse events (AEs) in animals and on establishing their correlation with different measures of drug exposure (e.g., C{sub max} and AUC). Such correlations, however, ignore the role of biomarkers, which can provide further insight into the underlying pharmacological mechanisms. Here we use naproxen as a paradigm drug to explore the feasibility of a biomarker-guided approach for the prediction of AEs in humans. A standard toxicology protocol was set up for the evaluation of effects of naproxen in rat, in which four doses were tested (7.5, 15,more » 40 and 80 mg/kg). In addition to sparse blood sampling for the assessment of exposure, thromboxane B{sub 2} and prostaglandin E{sub 2} were also collected in satellite groups. Nonlinear mixed effects modelling was used to evaluate the predictive performance of the approach. A one-compartmental model with first order absorption was found to best describe the pharmacokinetics of naproxen. A nonlinear relationship between dose and bioavailability was observed which leads to a less than proportional increase in naproxen concentrations with increasing doses. The pharmacodynamics of TXB{sub 2} and PGE{sub 2} was described by direct inhibition models with maximum pharmacological effects achieved at doses > 7.5 mg/kg. The predicted PKPD relationship in humans was within 10-fold of the values previously published. Moreover, our results indicate that biomarkers can be used to assess interspecies differences in PKPD and extrapolated data from animals to humans. Biomarker sampling should be used systematically in general toxicity studies. - Highlights: • Prediction of a drug's safety profile from preclinical protocols remains challenging. • Pharmacokinetic measures of safe exposure (e.g., AUC) ignore the role of biomarkers. • PKPD relationships enable the evaluation of adverse events in a mechanistic manner. • Major

  12. Photoactive platinum(II) complexes of nonsteroidal anti-inflammatory drug naproxen: Interaction with biological targets, antioxidant activity and cytotoxicity.

    PubMed

    Srivastava, Payal; Singh, Khushbu; Verma, Madhu; Sivakumar, Sri; Patra, Ashis K

    2018-01-20

    The effect on the therapeutic efficacy of Pt(II) complexes on combining non-steroidal anti-inflammatory drugs (NSAIDs) is an attractive strategy to circumvent chronic inflammation mediated by cancer and metastasis. Two square-planar platinum(II) complexes: [Pt(dach)(nap)Cl] (1) and [Pt(dach)(nap) 2 ] (2), where dach = (1R,2R)-dichloro(cyclohexane-1,2-diamine) and NSAID drug naproxen (nap), have been designed for studying their biological activity. The naproxen bound to the Pt(II) centre get released upon photoirradiation with low-power UV-A light as confirmed by the significant enhancement in emission intensities of the complexes. The compounds were evaluated for their photophysical properties, photostability, reactivity with 5'-guanosine monophophosphate (5'-GMP), interactions with CT-DNA and BSA, antioxidant activity and reactive oxygen species mediated photo-induced DNA damage properties. ESI-MS studies demonstrated the formation of bis-adduct with 5'-GMP and the formation of Pt II -DNA crosslinks by gel electrophoretic mobility shift assay and ITC studies. The interaction of the complexes 1 and 2 with the CT-DNA exhibits potential binding affinity (K b  ∼ 10 4  M -1 , K app ∼ 10 5  M -1 ), implying intercalation to CT-DNA through planar naphthyl ring of the complexes. Both the complexes also exhibit strong binding affinity towards BSA (K BSA ∼ 10 5  M -1 ). The complexes exhibit efficient DNA damage activity on irradiation at 365 nm via formation of singlet oxygen ( 1 O 2 ) and hydroxyl radical ( • OH) under physiological conditions. Both the complexes were cytotoxic in dark and exhibit significant enhancement of cytotoxicity upon photo-exposure against HeLa and HepG2 cancer cells giving IC 50 values ranging from 8 to 12 μM for 1 and 2. The cellular internalization data showed cytosolic and nuclear localization of the complexes in the HeLa cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Inequality in Participation in Adult Learning and Education (ALE): Effects of Micro- and Macro-Level Factors through a Comparative Study

    ERIC Educational Resources Information Center

    Lee, Jeongwoo

    2017-01-01

    The objectives of this dissertation include describing and analyzing the patterns of inequality in ALE participation at both the micro and macro levels. Special attention is paid to social origins of individual adults and their association with two groups of macro-level factors, social inequality (income, education, and skill inequality) and…

  14. In vivo effects of naproxen, salicylic acid, and valproic acid on the pharmacokinetics of trichloroethylene and metabolites in rats.

    PubMed

    Rouhou, Mouna Cheikh; Charest-Tardif, Ginette; Haddad, Sami

    2015-01-01

    It was recently demonstrated that some drugs modulate in vitro metabolism of trichloroethylene (TCE) in humans and rats. The objective was to assess in vivo interactions between TCE and three drugs: naproxen (NA), valproic acid (VA), and salicylic acid (SA). Animals were exposed to TCE by inhalation (50 ppm for 6 h) and administered a bolus dose of drug by gavage, equivalent to 10-fold greater than the recommended daily dose. Samples of blood, urine, and collected tissues were analyzed by headspace gas chromatography coupled to an electron capture detector for TCE and metabolites (trichloroethanol [TCOH] and trichloroacetate [TCA]) levels. Coexposure to NA and TCE significantly increased (up to 50%) total and free TCOH (TCOHtotal and TCOHfree, respectively) in blood. This modulation may be explained by an inhibition of glucuronidation. VA significantly elevated TCE levels in blood (up to 50%) with a marked effect on TCOHtotal excretion in urine but not in blood. In contrast, SA produced an increase in TCOHtotal levels in blood at 30, 60, and 90 min and urine after coexposure. Data confirm in vitro observations that NA, VA, and SA affect in vivo TCE kinetics. Future efforts need to be directed to evaluate whether populations chronically medicated with the considered drugs display greater health risks related to TCE exposure.

  15. Biophysical study of the non-steroidal anti-inflammatory drugs (NSAID) ibuprofen, naproxen and diclofenac with phosphatidylserine bilayer membranes.

    PubMed

    Manrique-Moreno, Marcela; Heinbockel, Lena; Suwalsky, Mario; Garidel, Patrick; Brandenburg, Klaus

    2016-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) represent an effective pain treatment option and therefore one of the most sold therapeutic agents worldwide. The study of the molecular interactions responsible for their physiological activity, but also for their side effects, is therefore important. This report presents data on the interaction of the most consumed NSAIDs (ibuprofen, naproxen and diclofenac) with one main phospholipid in eukaryotic cells, dimyristoylphosphatidylserine (DMPS). The applied techniques are Fourier-transform infrared spectroscopy (FTIR), with which in transmission the gel to liquid crystalline phase transition of the acyl chains in the absence and presence of the NSAID are monitored, supplemented by differential scanning calorimetry (DSC) data on the phase transition. FTIR in reflection (ATR, attenuated total reflectance) is applied to record the dependence of the interactions of the NSAID with particular functional groups observed in the DMPS spectrum such as the ester carbonyl and phosphate vibrational bands. With Förster resonance energy transfer (FRET) a possible intercalation of the NSAID into the DMPS liposomes and with isothermal titration calorimetry (ITC) the thermodynamics of the interaction are monitored. The data show that the NSAID react in a particular way with this lipid, but in some parameters the three NSAID clearly differ, with which now a clear picture of the interaction processes is possible. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Increased susceptibility of ethanol-treated gastric mucosa to naproxen and its inhibition by DA-9601, an Artemisia asiatica extract

    PubMed Central

    Oh, Tae Young; Ahn, Gook Jun; Choi, Seul Min; Ahn, Byoung Ok; Kim, Won Bae

    2005-01-01

    AIM: To examine the effect of DA-9601, a new gastroprotective agent, on the vulnerability of ethanol-treated rat’s stomach to naproxen (NAP). METHODS: Male Sprague-Dawley rats were pretreated with 1 mL of 50% ethanol twice a day for 5 d and then NAP (50 mg/kg) was administered. DA-9601 was administered 1 h before NAP. Four hours after NAP, the rats were killed to examine gross injury index (mm2), histologic change and to determine mucosal levels of malondialdehyde (MDA), prostaglandin E2 (PGE2), glutathione (GSH) and myeloperoxidase (MPO). RESULTS: Pretreatment of ethanol significantly increased NAP-induced gastric lesions, as well as an increase in MDA and MPO. On the contrary, mucosal PGE2 and GSH contents were decreased dramatically by ethanol pretreatment, which were aggravated by NAP. DA-9601 significantly reduced NAP-induced gastric injury grossly and microscopically, regardless of pretreatment with ethanol. DA-9601 preserved, or rather, increased mucosal PGE2 and GSH in NAP-treated rats (P<0.05), with reduction in mucosal MDA and MPO levels. CONCLUSION: These results suggest that repeated alcohol consumption renders gastric mucosa more susceptible to NSAIDs though, at least in part, reduction of endogenous cytoprotectants including PGE2 and GSH, and increase in MPO activation, and that DA-9601, a new gastroprotectant, can reduce the increased vulnerability of ethanol consumers to NSAIDs-induced gastric damage via the mechanism in which PGE2 and GSH are involved. PMID:16437715

  17. Gastroprotective properties of cashew gum, a complex heteropolysaccharide of Anacardium occidentale, in naproxen-induced gastrointestinal damage in rats.

    PubMed

    Carvalho, Nathalia S; Silva, Mônica M; Silva, Renan O; Nicolau, Lucas A D; Sousa, Francisca Beatriz M; Damasceno, Samara R B; Silva, Durcilene A; Barbosa, André L R; Leite, José Roberto S A; Medeiros, Jand Venes R

    2015-05-01

    Long-term use nonsteroidal anti-inflammatory drug is associated with gastrointestinal (GI) lesion formation. The aim of this study was to investigate the protective activity of cashew gum (CG), a complex heteropolysaccharide extracted from Anacardium occidentale on naproxen (NAP)-induced GI damage. Male Wistar rats were pretreated with vehicle or CG (1, 3, 10, and 30 mg/kg, p.o.) twice daily for 2 days; after 1 h, NAP (80 mg/kg, p.o.) was administered. The rats were euthanized on the 2nd day of treatment, 4 h after NAP administration. Stomach lesions were measured using digital calipers. The medial small intestine was used for the evaluation of macroscopic lesion scores. Samples of the stomach and the intestine were used for histological evaluation, and assays for glutathione (GSH), malonyldialdehyde (MDA), and myeloperoxidase (MPO). Additional rats were used to measure gastric mucus and secretion. Pretreatment with CG reduced the macroscopic and microscopic damage induced by NAP. CG significantly attenuated NAP-induced alterations in MPO, GSH, and MDA levels. Furthermore, CG returned adherent mucus levels to normal values. These results suggest that CG has a protective effect against GI damage via mechanisms that involve the inhibition of inflammation and increasing the amount of adherent mucus in mucosa. © 2015 Wiley Periodicals, Inc.

  18. Degradation of naproxen and carbamazepine in spiked sludge by slurry and solid-phase Trametes versicolor systems.

    PubMed

    Rodríguez-Rodríguez, Carlos E; Marco-Urrea, Ernest; Caminal, Gloria

    2010-04-01

    Growth and activity of the white-rot fungus Trametes versicolor on sewage sludge were assessed in bioslurry and solid-phase systems. Bioslurry cultures with different loads of sludge (10%, 25% and 38%, w/v) were performed. A lag phase of at least 2 d appeared in the 25 and 38%-cultures, however, the total fungal biomass was higher for the latter and lower for the 10%-culture after 30 d, as revealed by ergosterol determination. Detectable laccase activity levels were found in the 10 and 25%-cultures (up to 1308 and 2588 AUL(-1), respectively) while it was negligible in the 38%-culture. Important levels of ergosterol and laccase were obtained over a 60 d period in sludge solid-phase cultures amended with different concentrations of wheat straw pellets as lignocellulosic bulking material. Degradation experiments in 25%-bioslurry cultures spiked with naproxene (NAP, analgesic) and carbamazepine (CBZ, antiepileptic) showed depletion of around 47% and 57% within 24h, respectively. Complete depletion of NAP and around 48% for CBZ were achieved within 72 h in sludge solid cultures with 38% bulking material. CBZ degradation is especially remarkable due to its high persistence in wastewater treatment plants. Results showed that T. versicolor may be an interesting bioremediation agent for elimination of emerging pollutants in sewage sludge. Copyright 2009 Elsevier Ltd. All rights reserved.

  19. Increased susceptibility of ethanol-treated gastric mucosa to naproxen and its inhibition by DA-9601, an Artemisia asiatica extract.

    PubMed

    Oh, Tae Young; Ahn, Gook Jun; Choi, Seul Min; Ahn, Byoung Ok; Kim, Won Bae

    2005-12-21

    To examine the effect of DA-9601, a new gastroprotective agent, on the vulnerability of ethanol-treated rat's stomach to naproxen (NAP). Male Sprague-Dawley rats were pretreated with 1 mL of 50% ethanol twice a day for 5 d and then NAP (50 mg/kg) was administered. DA-9601 was administered 1 h before NAP. Four hours after NAP, the rats were killed to examine gross injury index (mm2), histologic change and to determine mucosal levels of malondialdehyde (MDA), prostaglandin E2 (PGE2), glutathione (GSH) and myeloperoxidase (MPO). Pretreatment of ethanol significantly increased NAP-induced gastric lesions, as well as an increase in MDA and MPO. On the contrary, mucosal PGE2 and GSH contents were decreased dramatically by ethanol pretreatment, which were aggravated by NAP. DA-9601 significantly reduced NAP-induced gastric injury grossly and microscopically, regardless of pretreatment with ethanol. DA-9601 preserved, or rather, increased mucosal PGE2 and GSH in NAP-treated rats (P<0.05), with reduction in mucosal MDA and MPO levels. These results suggest that repeated alcohol consumption renders gastric mucosa more susceptible to NSAIDs though, at least in part, reduction of endogenous cytoprotectants including PGE2 and GSH, and increase in MPO activation, and that DA-9601, a new gastroprotectant, can reduce the increased vulnerability of ethanol consumers to NSAIDs-induced gastric damage via the mechanism in which PGE2 and GSH are involved.

  20. Hydrogen sulfide-releasing naproxen suppresses colon cancer cell growth and inhibits NF-κB signaling.

    PubMed

    Kodela, Ravinder; Nath, Niharika; Chattopadhyay, Mitali; Nesbitt, Diandra E; Velázquez-Martínez, Carlos A; Kashfi, Khosrow

    2015-01-01

    Colorectal cancer (CRC) is the second leading cause of death due to cancer and the third most common cancer in men and women in the USA. Nuclear factor kappa B (NF-κB) is known to be activated in CRC and is strongly implicated in its development and progression. Therefore, activated NF-κB constitutes a bona fide target for drug development in this type of malignancy. Many epidemiological and interventional studies have established nonsteroidal anti-inflammatory drugs (NSAIDs) as a viable chemopreventive strategy against CRC. Our previous studies have shown that several novel hydrogen sulfide-releasing NSAIDs are promising anticancer agents and are safer derivatives of NSAIDs. In this study, we examined the growth inhibitory effect of a novel H2S-releasing naproxen (HS-NAP), which has a repertoire as a cardiovascular-safe NSAID, for its effects on cell proliferation, cell cycle phase transitions, and apoptosis using HT-29 human colon cancer cells. We also investigated its effect as a chemo-preventive agent in a xenograft mouse model. HS-NAP suppressed the growth of HT-29 cells by induction of G0/G1 arrest and apoptosis and downregulated NF-κB. Tumor xenografts in mice were significantly reduced in volume. The decrease in tumor mass was associated with a reduction of cell proliferation, induction of apoptosis, and decreases in NF-κB levels in vivo. Therefore, HS-NAP demonstrates strong anticancer potential in CRC.

  1. Drop Printing of Pharmaceuticals: Effect of Molecular Weight on PEG Coated-Naproxen/PEG3350 Solid Dispersions

    PubMed Central

    Hsu, Hsin-Yun; Toth, Scott; Simpson, Garth J.; Harris, Michael T.

    2016-01-01

    Solid dispersions have been used to enhance the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the solid state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the Drop Printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two/three dimensional structures. In this study, DP was used to prepare naproxen (NAP)/polyethylene glycol 3350 (PEG3350) solid dispersions with PEG coatings of different molecular weights (MW). A comparison of moisture-accelerated crystallization inhibition by different PEG coatings was assessed. Scanning electron microscopy (SEM), second harmonic generation (SHG) microscopy, and differential scanning calorimetry (DSC) analysis were performed to characterize the morphology and quantify the apparent crystallinity of NAP within the solid dispersions. Thermogravimetric analysis (TGA) was employed to measure the water content within each sample. The results suggest that the moisture-accelerated crystallization inhibition capability of the PEG coatings increased with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of DP technology on manufacturing formulation, multilayer tablets with different PEG serving as barrier layers were also constructed, and their dissolution behavior was examined. By applying DP and appropriate materials, it is possible to design various carrier devices used to control the release dynamics of the API. PMID:27041744

  2. Drop Printing of Pharmaceuticals: Effect of Molecular Weight on PEG Coated-Naproxen/PEG3350 Solid Dispersions.

    PubMed

    Hsu, Hsin-Yun; Toth, Scott; Simpson, Garth J; Harris, Michael T

    2015-12-01

    Solid dispersions have been used to enhance the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the solid state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the Drop Printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two/three dimensional structures. In this study, DP was used to prepare naproxen (NAP)/polyethylene glycol 3350 (PEG3350) solid dispersions with PEG coatings of different molecular weights (MW). A comparison of moisture-accelerated crystallization inhibition by different PEG coatings was assessed. Scanning electron microscopy (SEM), second harmonic generation (SHG) microscopy, and differential scanning calorimetry (DSC) analysis were performed to characterize the morphology and quantify the apparent crystallinity of NAP within the solid dispersions. Thermogravimetric analysis (TGA) was employed to measure the water content within each sample. The results suggest that the moisture-accelerated crystallization inhibition capability of the PEG coatings increased with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of DP technology on manufacturing formulation, multilayer tablets with different PEG serving as barrier layers were also constructed, and their dissolution behavior was examined. By applying DP and appropriate materials, it is possible to design various carrier devices used to control the release dynamics of the API.

  3. Reduction of atmospheric disturbances in PSInSAR measure technique based on ENVISAT ASAR data for Erta Ale Ridge

    NASA Astrophysics Data System (ADS)

    Kopeć, Anna

    2018-01-01

    The interferometric synthetic aperture radar (InSAR) is becoming more and more popular to investigate surface deformation, associated with volcanism, earthquakes, landslides, and post-mining surface subsidence. The measuring accuracy depends on many factors: surface, time and geometric decorrelation, orbit errors, however the largest challenges are the tropospheric delays. The spatial and temporal variations in temperature, pressure, and relative humidity are responsible for tropospheric delays. So far, many methods have been developed, but researchers are still searching for the one, that will allow to correct interferograms consistently in different regions and times. The article focuses on examining the methods based on empirical phase-based methods, spectrometer measurements and weather model. These methods were applied to the ENVISAT ASAR data for the Erta Ale Ridge in the Afar Depression, East Africa

  4. The role of the right temporoparietal junction in attention and social interaction as revealed by ALE meta-analysis

    PubMed Central

    Rottschy, C.; Oberwelland, E.; Bzdok, D.; Fox, P. T.; Eickhoff, S. B.; Fink, G. R.; Konrad, K.

    2016-01-01

    The right temporoparietal junction (rTPJ) is frequently associated with different capacities that to shift attention to unexpected stimuli (reorienting of attention) and to understand others’ (false) mental state [theory of mind (ToM), typically represented by false belief tasks]. Competing hypotheses either suggest the rTPJ representing a unitary region involved in separate cognitive functions or consisting of subregions subserving distinct processes. We conducted activation likelihood estimation (ALE) meta-analyses to test these hypotheses. A conjunction analysis across ALE meta-analyses delineating regions consistently recruited by reorienting of attention and false belief studies revealed the anterior rTPJ, suggesting an overarching role of this specific region. Moreover, the anatomical difference analysis unravelled the posterior rTPJ as higher converging in false belief compared with reorienting of attention tasks. This supports the concept of an exclusive role of the posterior rTPJ in the social domain. These results were complemented by meta-analytic connectivity mapping (MACM) and resting-state functional connectivity (RSFC) analysis to investigate whole-brain connectivity patterns in task-constrained and task-free brain states. This allowed for detailing the functional separation of the anterior and posterior rTPJ. The combination of MACM and RSFC mapping showed that the posterior rTPJ has connectivity patterns with typical ToM regions, whereas the anterior part of rTPJ co-activates with the attentional network. Taken together, our data suggest that rTPJ contains two functionally fractionated subregions: while posterior rTPJ seems exclusively involved in the social domain, anterior rTPJ is involved in both, attention and ToM, conceivably indicating an attentional shifting role of this region. PMID:24915964

  5. Different patterns and development characteristics of processing written logographic characters and alphabetic words: an ALE meta-analysis.

    PubMed

    Zhu, Linlin; Nie, Yaoxin; Chang, Chunqi; Gao, Jia-Hong; Niu, Zhendong

    2014-06-01

    The neural systems for phonological processing of written language have been well identified now, while models based on these neural systems are different for different language systems or age groups. Although each of such models is mostly concordant across different experiments, the results are sensitive to the experiment design and intersubject variability. Activation likelihood estimation (ALE) meta-analysis can quantitatively synthesize the data from multiple studies and minimize the interstudy or intersubject differences. In this study, we performed two ALE meta-analysis experiments: one was to examine the neural activation patterns of the phonological processing of two different types of written languages and the other was to examine the development characteristics of such neural activation patterns based on both alphabetic language and logographic language data. The results of our first meta-analysis experiment were consistent with the meta-analysis which was based on the studies published before 2005. And there were new findings in our second meta-analysis experiment, where both adults and children groups showed great activation in the left frontal lobe, the left superior/middle temporal gyrus, and the bilateral middle/superior occipital gyrus. However, the activation of the left middle/inferior frontal gyrus was found increase with the development, and the activation was found decrease in the following areas: the right claustrum and inferior frontal gyrus, the left inferior/medial frontal gyrus, the left middle/superior temporal gyrus, the right cerebellum, and the bilateral fusiform gyrus. It seems that adults involve more phonological areas, whereas children involve more orthographic areas and semantic areas. Copyright © 2013 Wiley Periodicals, Inc.

  6. Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized, double-blind pilot study.

    PubMed

    Levy, Robert M; Saikovsky, Roman; Shmidt, Evgeniya; Khokhlov, Alexander; Burnett, Bruce P

    2009-05-01

    Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P < or = .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.

  7. The anti-inflammatory drugs diclofenac, naproxen and ibuprofen are found in the bile of wild fish caught downstream of a wastewater treatment plant.

    PubMed

    Brozinski, Jenny-Maria; Lahti, Marja; Meierjohann, Axel; Oikari, Aimo; Kronberg, Leif

    2013-01-02

    Pharmaceutical residues are ubiquitous in rivers, lakes, and at coastal waters affected by discharges from municipal wastewater treatment plants. In this study, the presence of 17 different pharmaceuticals and six different phase I metabolites was determined in the bile of two wild fish species, bream (Abramis brama) and roach (Rutilus rutilus). The fish were caught from a lake that receives treated municipal wastewater via a small river. Prior to analyses, the bile content was enzymatically hydrolyzed to convert the glucuronide metabolites into the original pharmaceuticals or phase I metabolites. The solid phase extracts of hydrolyzates were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the multiple reaction monitoring mode. The anti-inflammatory drug naproxen could be detected in all the six bream and roach bile samples. Diclofenac was found in five of the bream and roach samples, while ibuprofen was detected in three bream and two roach samples. The observed bile concentrations of diclofenac, naproxen, and ibuprofen in bream ranged from 6 to 95 ng mL(-1), 6 to 32 ng mL(-1), and 16 to 34 ng mL(-1), respectively. The corresponding values in roach samples ranged from 44 to 148 ng mL(-1), 11 to 103 ng mL(-1) and 15 to 26 ng mL(-1), respectively. None of the other studied compounds could be detected. The study shows that pharmaceuticals originating from wastewater treatment plant effluents can be traced to the bile of wild bream and roach living in a lake where diclofenac, naproxen, and ibuprofen are present as pollutants.

  8. Pharmacologic Modulation of Hand Pain in Osteoarthritis: A Double-Blind Placebo-Controlled Functional Magnetic Resonance Imaging Study Using Naproxen

    PubMed Central

    Sanders, Duncan; Krause, Kristina; O'Muircheartaigh, Jonathan; Thacker, Michael A; Huggins, John P; Vennart, William; Massat, Nathalie J; Choy, Ernest; Williams, Steven C R; Howard, Matthew A

    2015-01-01

    Objective In an attempt to shed light on management of chronic pain conditions, there has long been a desire to complement behavioral measures of pain perception with measures of underlying brain mechanisms. Using functional magnetic resonance imaging (fMRI), we undertook this study to investigate changes in brain activity following the administration of naproxen or placebo in patients with pain related to osteoarthritis (OA) of the carpometacarpal (CMC) joint. Methods A placebo-controlled, double-blind, 2-period crossover study was performed in 19 individuals with painful OA of the CMC joint of the right hand. Following placebo or naproxen treatment periods, a functionally relevant task was performed, and behavioral measures of the pain experience were collected in identical fMRI examinations. Voxelwise and a priori region of interest analyses were performed to detect between-period differences in brain activity. Results Significant reductions in brain activity following treatment with naproxen, compared to placebo, were observed in brain regions commonly associated with pain perception, including the bilateral primary somatosensory cortex, thalamus, and amygdala. Significant relationships between changes in perceived pain intensity and changes in brain activity were also observed in brain regions previously associated with pain intensity. Conclusion This study demonstrates the sensitivity of fMRI to detect the mechanisms underlying treatments of known efficacy. The data illustrate the enticing potential of fMRI as an adjunct to self-report for detecting early signals of efficacy of novel therapies, both pharmacologic and nonpharmacologic, in small numbers of individuals with persistent pain. PMID:25533872

  9. Hyperbranched polyglycerol/graphene oxide nanocomposite reinforced hollow fiber solid/liquid phase microextraction for measurement of ibuprofen and naproxen in hair and waste water samples.

    PubMed

    Rezaeifar, Zohreh; Es'haghi, Zarrin; Rounaghi, Gholam Hossein; Chamsaz, Mahmoud

    2016-09-01

    A new design of hyperbranched polyglycerol/graphene oxide nanocomposite reinforced hollow fiber solid/liquid phase microextraction (HBP/GO -HF-SLPME) coupled with high performance liquid chromatography used for extraction and determination of ibuprofen and naproxen in hair and waste water samples. The graphene oxide first synthesized from graphite powders by using modified Hummers approach. The surface of graphene oxide was modified using hyperbranched polyglycerol, through direct polycondensation with thionyl chloride. The ready nanocomposite later wetted by a few microliter of an organic solvent (1-octanol), and then applied to extract the target analytes in direct immersion sampling mode.After the extraction process, the analytes were desorbed with methanol, and then detected via high performance liquid chromatography (HPLC). The experimental setup is very simple and highly affordable. The main factors influencing extraction such as; feed pH, extraction time, aqueous feed volume, agitation speed, the amount of functionalized graphene oxide and the desorption conditions have been examined in detail. Under the optimized experimental conditions, linearity was observed in the range of 5-30,000ngmL(-1) for ibuprofen and 2-10,000ngmL(-1) for naproxen with correlation coefficients of 0.9968 and 0.9925, respectively. The limits of detection were 2.95ngmL(-1) for ibuprofen and 1.51ngmL(-1) for naproxen. The relative standard deviations (RSDs) were found to be less than 5% (n=5). Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Supramolecular solid-phase extraction of ibuprofen and naproxen from sewage based on the formation of mixed supramolecular aggregates prior to their liquid chromatographic/photometric determination.

    PubMed

    Costi, Esther María; Goryacheva, Irina; Sicilia, María Dolores; Rubio, Soledad; Pérez-Bendito, Dolores

    2008-11-07

    Sorbents made up of sodium dodecyl sulphate (SDS) hemimicelles, formed onto gamma-alumina, were proposed for the quantitative and practically solvent-free solid-phase extraction (SPE) of ibuprofen and naproxen from sewage samples. The formation of drug-SDS mixed aggregates was proved by the pseudophase separation model and their composition as a function of the amount of drug was calculated. The overall hemimicellar SPE procedure consumed only 0.6 mL of methanol since non-organic solvent was required for cartridge conditioning and the drugs were completely eluted using 2 mL of a 0.3M NaOH:methanol (70:30, v/v) solution. Breakthrough volumes of around 0.75 L and above 1L were obtained for naproxen and ibuprofen, respectively. No clean-up steps were necessary for the determination of these drugs in sewage because the direct analysis of the eluates by liquid chromatography/UV was matrix effect-free. The identification of the analytes was based on retention times and UV spectra and it was confirmed by on-line fluorescence detection. The detection limits for naproxen and ibuprofen were 0.8 and 9 ng L(-1) in wastewater influents and 0.5 and 7 ng L(-1) in effluents, respectively. These limits were similar to or lower than those achieved by methods based on conventional sorbents (e.g. C(18)-silica or polymeric resins), which invariably require the evaporation of the eluates. The accuracy and precision of the proposed method were assessed by analysing influent and effluent wastewater samples spiked with 2 and 0.4 microg L(-1) of each analyte, respectively. The recoveries obtained and the corresponding standard deviations were in the ranges 93-101% and 2-9%. The method was applied to the determination of the target drugs in wastewater from three sewage treatment plants (STPs) in the south of Spain. The concentration of ibuprofen and naproxen ranged between 2.0 and 7.4 microg L(-1) and 0.9 and 3.3 microg L(-1) in influents and 0.4 and 1.4 microg L(-1) and 0.2 and 0.8 microg L

  11. Longitudinal numbers-needed-to-treat (NNT) for achieving various levels of analgesic response and improvement with etoricoxib, naproxen, and placebo in ankylosing spondylitis.

    PubMed

    Peloso, Paul M; Gammaitoni, Arnold; Smugar, Steven S; Wang, Hongwei; Moore, Andrew R

    2011-07-18

    Clinical analgesic trials typically report response as group mean results. However, research has shown that few patients are average and most have responses at the extremes. Moreover, group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level. Responder analyses and numbers-needed-to-treat (NNT) are considered more relevant for evaluating treatment response. We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score improvement and the associated NNTs. This was a post-hoc analysis of a 6-week, randomized, double-blind study (N = 387) comparing etoricoxib 90 mg, etoricoxib 120 mg, naproxen 1000 mg, and placebo in AS. Spine pain and BASDAI were measured on a 100-mm visual analog scale. The number and percentage of patients achieving ≥30% and ≥50% improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs. Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation. For etoricoxib 90 mg, etoricoxib 120 mg and naproxen 1000 mg, the NNTs at 6 weeks compared with placebo were 2.0, 2.0, and 2.7 respectively for BASDAI ≥30% improvement, and 3.2, 2.8, and 4.1 for ≥50% improvement. For spine pain, the NNTs were 1.9, 2.0, and 3.2, respectively, for ≥30% improvement, and 2.7, 2.5, and 3.7 for ≥50% improvement. The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinically meaningful difference for pain. Response rates and NNTs were generally similar and stable over 2, 4, and 6 weeks. For every 2 patients treated with etoricoxib, 1 achieved a clinically meaningful (≥30%) improvement in spine pain and BASDAI beyond that expected from placebo, whereas the corresponding values were approximately 1 in every 3 patients treated with naproxen. Use of NNTs and responder analyses provide

  12. Changes in the solid state of anhydrous and hydrated forms of sodium naproxen under different grinding and environmental conditions: Evidence of the formation of new hydrated forms.

    PubMed

    Censi, Roberta; Rascioni, Riccardo; Di Martino, Piera

    2015-05-01

    The aim of the present work was to investigate the solid state change of the anhydrous and hydrate solid forms of sodium naproxen under different grinding and environmental conditions. Grinding was carried out manually in a mortar under the following conditions: at room temperature under air atmosphere (Method A), in the presence of liquid nitrogen under air atmosphere (Method B), at room temperature under nitrogen atmosphere (Method C), and in the presence of liquid nitrogen under nitrogen atmosphere (Method D). Among the hydrates, the following forms were used: a dihydrate form (DSN) obtained by exposing the anhydrous form at 55% RH; a dihydrate form (CSN) obtained by crystallizing sodium naproxen from water; the tetrahydrate form (TSN) obtained by exposing the anhydrous form at 75% RH. The metastable monohydrate form (MSN), previously described in the literature, was not used because of its high physical instability. The chemical stability during grinding was firstly assessed and proven by HPLC. Modification of the particle size and shape, and changes in the solid state under different grinding methods were evaluated by scanning electron microscopy, and X-ray powder diffractometry and thermogravimetry, respectively. The study demonstrated the strong influence of starting form, grinding and environmental conditions on particle size, shape and solid state of recovered sodium naproxen forms. In particular, it was demonstrated that in the absence of liquid nitrogen (Methods A and C), either at air or at nitrogen atmosphere, the monohydrate form (MSN) was obtained from any hydrates, meaning that these grinding conditions favored the dehydration of superior hydrates. The grinding process carried out in the presence of liquid nitrogen (Method B) led to further hydration of the starting materials: new hydrate forms were identified as one pentahydrate form and one hexahydrate form. The hydration was caused by the condensation of the atmospheric water on sodium naproxen

  13. Longitudinal Numbers-Needed-To-Treat (NNT) for Achieving Various Levels of Analgesic Response and Improvement with Etoricoxib, Naproxen, and Placebo in Ankylosing Spondylitis

    PubMed Central

    2011-01-01

    Background Clinical analgesic trials typically report response as group mean results. However, research has shown that few patients are average and most have responses at the extremes. Moreover, group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level. Responder analyses and numbers-needed-to-treat (NNT) are considered more relevant for evaluating treatment response. We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score improvement and the associated NNTs. Methods This was a post-hoc analysis of a 6-week, randomized, double-blind study (N = 387) comparing etoricoxib 90 mg, etoricoxib 120 mg, naproxen 1000 mg, and placebo in AS. Spine pain and BASDAI were measured on a 100-mm visual analog scale. The number and percentage of patients achieving ≥30% and ≥50% improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs. Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation. Results For etoricoxib 90 mg, etoricoxib 120 mg and naproxen 1000 mg, the NNTs at 6 weeks compared with placebo were 2.0, 2.0, and 2.7 respectively for BASDAI ≥30% improvement, and 3.2, 2.8, and 4.1 for ≥50% improvement. For spine pain, the NNTs were 1.9, 2.0, and 3.2, respectively, for ≥30% improvement, and 2.7, 2.5, and 3.7 for ≥50% improvement. The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinically meaningful difference for pain. Response rates and NNTs were generally similar and stable over 2, 4, and 6 weeks. Conclusions For every 2 patients treated with etoricoxib, 1 achieved a clinically meaningful (≥30%) improvement in spine pain and BASDAI beyond that expected from placebo, whereas the corresponding values were approximately 1 in every 3 patients treated with naproxen. Use of

  14. Different effects of the nonsteroidal anti-inflammatory drugs meclofenamate sodium and naproxen sodium on proteasome activity in cardiac cells.

    PubMed

    Ghosh, Rajeshwary; Hwang, Soyun M; Cui, Ziyou; Gilda, Jennifer E; Gomes, Aldrin V

    2016-05-01

    The use of nonsteroidal anti-inflammatory drugs (NSAIDs) like meclofenamate sodium (MS), used to reduce pain, has been associated with an increased risk of cardiovascular disease (CVD). Naproxen (NAP), another NSAID, is not associated with increased risk of CVD. The molecular mechanism(s) by which NSAIDs induce CVD is unknown. We investigated the effects of MS and NAP on protein homeostasis and cardiotoxicity in rat cardiac H9c2 cells and murine neonatal cardiomyocytes. MS, but not NAP, significantly inhibited proteasome activity and reduced cardiac cell viability at pharmacological levels found in humans. Although proteasome subunit gene and protein expression were unaffected by NSAIDs, MS treated cell lysates showed higher 20S proteasome content, while purified proteasomes from MS treated cells had lower proteasome activity and higher levels of oxidized subunits than proteasomes from control cells. Addition of exogenous proteasome to MS treated cells improved cell viability. Both MS and NAP increased ROS production, but the rate of ROS production was greater in MS than in NAP treated cells. The ROS production is likely from mitochondria, as MS inhibited mitochondrial Complexes I and III, major sources of ROS, while NAP inhibited Complex I. MS also impaired mitochondrial membrane potential while NAP did not. Antioxidants were able to prevent the reduced cell viability caused by MS treatment. These results suggest that NSAIDs induce cardiotoxicity by a ROS dependent mechanism involving mitochondrial and proteasome dysfunction and may explain why some NSAIDs should not be given to patients for long periods. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. UV and solar photo-degradation of naproxen: TiO₂ catalyst effect, reaction kinetics, products identification and toxicity assessment.

    PubMed

    Jallouli, Nabil; Elghniji, Kais; Hentati, Olfa; Ribeiro, Ana R; Silva, Adrián M T; Ksibi, Mohamed

    2016-03-05

    Direct photolysis and TiO2-photocatalytic degradation of naproxen (NPX) in aqueous solution were studied using a UV lamp and solar irradiation. The degradation of NPX was found to be in accordance with pseudo-first order kinetics, the photocatalytic process being more efficient than photolysis. The NPX removal by photolysis (pHinitial 6.5) was 83% after 3h, with 11% of chemical oxygen demand (COD) reduction, whereas the TiO2-UV process led to higher removals of both NPX (98%) and COD (25%). The apparent pseudo-first-order rate constant (kapp) for NPX degradation by photolysis ranged from 0.0050 min(-1) at pH 3.5 to 0.0095 min(-1) at pH 6.5, while it was estimated to be 0.0063 min(-1) under acidic conditions in photocatalysis, increasing by 4-fold at pH 6.5. Ultra High Performance Liquid chromatography (UHPLC) coupled with a triple quadrupole detector and also a hybrid mass spectrometer which combines the linear ion trap triple quadrupole (LTQ) and OrbiTrap mass analyser, were used to identify NPX degradation products. The main intermediates detected were 1-(6-methoxynaphtalene-2-yl) ethylhydroperoxide, 2-ethyl-6-methoxynaphthalene, 1-(6-methoxynaphtalen-2-yl) ethanol, 1-(6-methoxynaphtalen-2-yl) ethanone and malic acid. Solar photocatalysis of NPX showed COD removals of 33% and 65% after 3 and 4h of treatment, respectively, and some reduction of acute toxicity, evaluated by the exposure of Eisenia andrei to OECD soils spiked with NPX-treated solutions. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Assessing the phototransformation of diclofenac, clofibric acid and naproxen in surface waters: Model predictions and comparison with field data.

    PubMed

    Avetta, Paola; Fabbri, Debora; Minella, Marco; Brigante, Marcello; Maurino, Valter; Minero, Claudio; Pazzi, Marco; Vione, Davide

    2016-11-15

    Phototransformation is important for the fate in surface waters of the pharmaceuticals diclofenac (DIC) and naproxen (NAP) and for clofibric acid (CLO), a metabolite of the drug clofibrate. The goal of this paper is to provide an overview of the prevailing photochemical processes, which these compounds undergo in the different conditions found in freshwater environments. The modelled photochemical half-life times of NAP and DIC range from a few days to some months, depending on water conditions (chemistry and depth) and on the season. The model indicates that direct photolysis is the dominant degradation pathway of DIC and NAP in sunlit surface waters, and potentially toxic cyclic amides were detected as intermediates of DIC direct phototransformation. With modelled half-life times in the month-year range, CLO is predicted to be more photostable than DIC or NAP and to be degraded mainly by reaction with the • OH radical and with the triplet states of chromophoric dissolved organic matter ( 3 CDOM*). The CLO intermediates arising from these processes and detected in this study (hydroquinone and 4-chlorophenol) are, respectively, a chronic toxicant to aquatic organisms and a possible carcinogen for humans. Hydroquinone is formed with only ∼5% yield upon CLO triplet-sensitised transformation, but it is highly toxic for algae and crustaceans. In contrast, the formation yield of 4-chlorophenol reaches ∼50% upon triplet sensitisation and ∼10% by · OH reaction. The comparison of model predictions with field data from a previous study yielded a very good agreement in the case of DIC and, when using 4-carboxybenzophenone as proxy for triplet sensitisation by CDOM, a good agreement was found for CLO as well. In the case of NAP, the comparison with field data suggests that its direct photolysis quantum yield approaches or even falls below the lower range of literature values. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Epiisopiloturine hydrochloride, an imidazole alkaloid isolated from Pilocarpus microphyllus leaves, protects against naproxen-induced gastrointestinal damage in rats.

    PubMed

    Nicolau, Lucas A D; Carvalho, Nathalia S; Pacífico, Dvison M; Lucetti, Larisse T; Aragão, Karoline S; Véras, Leiz M C; Souza, Marcellus H L P; Leite, José R S A; Medeiros, Jand Venes R

    2017-03-01

    This study aimed to investigate the protective effect of epiisopiloturine hydrochloride (EPI), an imidazole alkaloid, on NAP-induced gastrointestinal damage in rats. Initially, rats were pretreated with 0.5% carboxymethylcellulose (vehicle) or EPI (3, 10 and 30mg/kg, p.o. or i.p., groups 3-5, respectively) twice daily, for 2days. After 1h, NAP (80mg/kg, p.o.) was given. The control group received only vehicle (group 1) or vehicle+naproxen (group 2). Rats were euthanized on 2nd day, 4h after NAP treatment. Stomachs lesions were measured. Samples were collected for histological evaluation and glutathione (GSH), malonyldialdehyde (MDA), myeloperoxidase (MPO), and cytokines levels. Moreover, gastric mucosal blood flow (GMBF) was evaluated. EPI pretreatment prevented NAP-induced macro and microscopic gastric damage with a maximal effect at 10mg/kg. Histological analysis revealed that EPI decreased scores of damage caused by NAP. EPI reduced MPO (3.4±0.3U/mg of gastric tissue) and inhibited changes in MDA (70.4±8.3mg/g of gastric tissue) and GSH (246.2±26.4mg/g of gastric tissue). NAP increased TNF-α levels, and this effect was reduced by EPI pretreatment. Furthermore, EPI increased GMBF by 15% compared with the control group. Our data show that EPI protects against NAP-induced gastric and intestinal damage by reducing pro-inflammatory cytokines, reducing oxidative stress, and increasing GMBF. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Effect of Disease-Related Changes in Plasma Albumin on the Pharmacokinetics of Naproxen in Male and Female Arthritic Rats

    PubMed Central

    Li, Xiaonan; DuBois, Debra C.; Almon, Richard R.

    2017-01-01

    Naproxen (NPX) is used in the treatment of rheumatoid arthritis (RA) for alleviation of pain and inflammation. In view of the extensive albumin binding of NPX, this study investigates whether chronic inflammation and sex influence the physiologic albumin concentrations, plasma protein binding, and pharmacokinetics (PK) of NPX. The PK of NPX was evaluated in a rat model of RA [collagen-induced arthritis (CIA) in Lewis rats] and in healthy controls. These PK studies included 1) NPX in female and male CIA rats that received 10, 25, or 50 mg/kg NPX i.p.; and 2) NPX in healthy female and male rats after i.p. dosing of NPX at 50 mg/kg. Plasma albumin concentrations were quantified by enzyme-linked immunosorbent assay, and protein binding was assessed using ultrafiltration. The NPX concentrations in plasma and filtrates were determined by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Plasma concentration-time data of NPX were first assessed by noncompartmental analysis (NCA). Nonlinear PK as indicated by dose-dependent NCA clearances and distribution volumes was observed. A two-compartment model with a first-order absorption process incorporating nonlinear protein binding in plasma and tissues jointly described the PK data of all groups. Saturable albumin binding accounts for the nonlinearity of NPX PK in all rats as well as part of the PK differences in arthritic rats. The CIA rats exhibited reduced albumin concentrations, reduced overall protein binding, and reduced clearances of unbound NPX, consistent with expectations during inflammation. The net effect of chronic inflammation was an elevation of the Cmax and area under the plasma concentration-time curve (AUC) of unbound drug. PMID:28246126

  19. Extending ALE3D, an Arbitrarily Connected hexahedral 3D Code, to Very Large Problem Size (U)

    SciTech Connect

    Nichols, A L

    2010-12-15

    As the number of compute units increases on the ASC computers, the prospect of running previously unimaginably large problems is becoming a reality. In an arbitrarily connected 3D finite element code, like ALE3D, one must provide a unique identification number for every node, element, face, and edge. This is required for a number of reasons, including defining the global connectivity array required for domain decomposition, identifying appropriate communication patterns after domain decomposition, and determining the appropriate load locations for implicit solvers, for example. In most codes, the unique identification number is defined as a 32-bit integer. Thus the maximum valuemore » available is 231, or roughly 2.1 billion. For a 3D geometry consisting of arbitrarily connected hexahedral elements, there are approximately 3 faces for every element, and 3 edges for every node. Since the nodes and faces need id numbers, using 32-bit integers puts a hard limit on the number of elements in a problem at roughly 700 million. The first solution to this problem would be to replace 32-bit signed integers with 32-bit unsigned integers. This would increase the maximum size of a problem by a factor of 2. This provides some head room, but almost certainly not one that will last long. Another solution would be to replace all 32-bit int declarations with 64-bit long long declarations. (long is either a 32-bit or a 64-bit integer, depending on the OS). The problem with this approach is that there are only a few arrays that actually need to extended size, and thus this would increase the size of the problem unnecessarily. In a future computing environment where CPUs are abundant but memory relatively scarce, this is probably the wrong approach. Based on these considerations, we have chosen to replace only the global identifiers with the appropriate 64-bit integer. The problem with this approach is finding all the places where data that is specified as a 32-bit integer needs to

  20. An Examination of the Phase Transition Thermodynamics of (S)- and (RS)-Naproxen as a Basis for the Design of Enantioselective Crystallization Processes.

    PubMed

    Buchholz, Hannes; Emel'yanenko, Vladimir N; Lorenz, Heike; Verevkin, Sergey P

    2016-05-01

    A detailed experimental analysis of the phase transition thermodynamics of (S)-naproxen and (RS)-naproxen is reported. Vapor pressures were determined experimentally via the transpiration method. Sublimation enthalpies were obtained from the vapor pressures and from independent TGA measurements. Thermodynamics of fusion which have been well-studied in the literature were systematically remeasured by DSC. Both sublimation and fusion enthalpies were adjusted to one reference temperature, T = 298 K, using measured heat capacities of the solid and the melt phase by DSC. Average values from the measurements and from literature data were suggested for the sublimation and fusion enthalpies. In order to prove consistency of the proposed values the vaporization enthalpies obtained by combination of both were compared to vaporization enthalpies obtained by the group-additivity method and the correlation-gas chromatography method. The importance of reliable and precise phase transition data for thermochemical calculations such as the prediction of solid/liquid phase behaviour of chiral compounds is highlighted. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  1. Hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl thioester by Carica papaya lipase in water-saturated organic solvents.

    PubMed

    Ng, I-Son; Tsai, Shau-Wei

    2005-01-05

    For the first time, the Carica papaya lipase (CPL) stored in crude papain is explored as a potential enantioselective biocatalyst for obtaining chiral acids from their racemic thioesters. Hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl thioester in water-saturated organic solvents is employed as a model system for studying the effects of temperature and solvents on lipase activity and enantioselectivity. An optimal temperature of 60 degrees C, based on the initial rate of (S)-thioester and a high enantiomeric ratio (i.e., E-value defined as the ratio of initial rates for both substrates) of >100 at 45 degrees C in isooctane, is obtained. Kinetic analysis, considering product inhibition and enzyme deactivation, is also performed, showing agreement between the experimental and best-fit conversions for (S)-thioester. A comparison of the kinetic and thermodynamic behaviors of CPL and Candida rugosa lipase (CRL) in isooctane and cyclohexane indicates that both lipases are very similar in terms of thermodynamic parameters DeltaDeltaH and DeltaDeltaS, initial rate of (S)-substrate, and E-value when (R,S)-naproxen 2,2,2-trifluoroethyl thioester or ester is employed as substrate. (c) 2004 Wiley Periodicals, Inc.

  2. Comparison of the LLNL ALE3D and AKTS Thermal Safety Computer Codes for Calculating Times to Explosion in ODTX and STEX Thermal Cookoff Experiments

    SciTech Connect

    Wemhoff, A P; Burnham, A K

    2006-04-05

    Cross-comparison of the results of two computer codes for the same problem provides a mutual validation of their computational methods. This cross-validation exercise was performed for LLNL's ALE3D code and AKTS's Thermal Safety code, using the thermal ignition of HMX in two standard LLNL cookoff experiments: the One-Dimensional Time to Explosion (ODTX) test and the Scaled Thermal Explosion (STEX) test. The chemical kinetics model used in both codes was the extended Prout-Tompkins model, a relatively new addition to ALE3D. This model was applied using ALE3D's new pseudospecies feature. In addition, an advanced isoconversional kinetic approach was used in the AKTSmore » code. The mathematical constants in the Prout-Tompkins code were calibrated using DSC data from hermetically sealed vessels and the LLNL optimization code Kinetics05. The isoconversional kinetic parameters were optimized using the AKTS Thermokinetics code. We found that the Prout-Tompkins model calculations agree fairly well between the two codes, and the isoconversional kinetic model gives very similar results as the Prout-Tompkins model. We also found that an autocatalytic approach in the beta-delta phase transition model does affect the times to explosion for some conditions, especially STEX-like simulations at ramp rates above 100 C/hr, and further exploration of that effect is warranted.« less

  3. A multi-dimensional high-order DG-ALE method based on gas-kinetic theory with application to oscillating bodies

    NASA Astrophysics Data System (ADS)

    Ren, Xiaodong; Xu, Kun; Shyy, Wei

    2016-07-01

    This paper presents a multi-dimensional high-order discontinuous Galerkin (DG) method in an arbitrary Lagrangian-Eulerian (ALE) formulation to simulate flows over variable domains with moving and deforming meshes. It is an extension of the gas-kinetic DG method proposed by the authors for static domains (X. Ren et al., 2015 [22]). A moving mesh gas kinetic DG method is proposed for both inviscid and viscous flow computations. A flux integration method across a translating and deforming cell interface has been constructed. Differently from the previous ALE-type gas kinetic method with piecewise constant mesh velocity at each cell interface within each time step, the mesh velocity variation inside a cell and the mesh moving and rotating at a cell interface have been accounted for in the finite element framework. As a result, the current scheme is applicable for any kind of mesh movement, such as translation, rotation, and deformation. The accuracy and robustness of the scheme have been improved significantly in the oscillating airfoil calculations. All computations are conducted in a physical domain rather than in a reference domain, and the basis functions move with the grid movement. Therefore, the numerical scheme can preserve the uniform flow automatically, and satisfy the geometric conservation law (GCL). The numerical accuracy can be maintained even for a largely moving and deforming mesh. Several test cases are presented to demonstrate the performance of the gas-kinetic DG-ALE method.

  4. Comparison of ALE and SPH Simulations of Vertical Drop Tests of a Composite Fuselage Section into Water

    NASA Technical Reports Server (NTRS)

    Jackson, Karen E.; Fuchs, Yvonne T.

    2008-01-01

    Simulation of multi-terrain impact has been identified as an important research area for improved prediction of rotorcraft crashworthiness within the NASA Subsonic Rotary Wing Aeronautics Program on Rotorcraft Crashworthiness. As part of this effort, two vertical drop tests were conducted of a 5-ft-diameter composite fuselage section into water. For the first test, the fuselage section was impacted in a baseline configuration without energy absorbers. For the second test, the fuselage section was retrofitted with a composite honeycomb energy absorber. Both tests were conducted at a nominal velocity of 25-ft/s. A detailed finite element model was developed to represent each test article and water impact was simulated using both Arbitrary Lagrangian Eulerian (ALE) and Smooth Particle Hydrodynamics (SPH) approaches in LS-DYNA, a nonlinear, explicit transient dynamic finite element code. Analytical predictions were correlated with experimental data for both test configurations. In addition, studies were performed to evaluate the influence of mesh density on test-analysis correlation.

  5. Examination of tracer transport in the NCAR CCM2 by comparison of CFCl3 simulations with ALE/GAGE observations

    NASA Technical Reports Server (NTRS)

    Hartley, Dana E.; Williamson, David L.; Rasch, Philip J.; Prinn, Ronald G.

    1994-01-01

    The latest version of the National Center for Atmospheric Research (NCAR) community climate model (CCM2) contains a semi-Lagrangian tracer transport scheme for the purpose of advecting water vapor and for including chemistry in the climate model. One way to diagnose the CCM2 transport is to simulate CFCl3 in the CCM2 since it has a well-known industry-based source distribution and a photochemical sink and to compare the model results to Atmospheric Lifetime Experiment/Global Atmospheric Gases Experiment ALE/GAGE observations around the globe. In this paper we focus on this comparison and discuss the synoptic scale issues of tracer transport where appropriate. We compare the model and observations on both 12-hour and monthly timescales. The higher-frequency events allow us to diagnose the synoptic scale transport in the CCM2 associated with the observational sites and to determine uncertainties in our high-resolution source distribution. We find that the CCM2 does simulate many of the key features such as pollution events and some seasonal transports, but there are still some dynamical features of tracer transport such as the storm track dynamics and cross-equatorial flow that merit further study in both the model and the real atmosphere.

  6. Ultrasound-assisted magnetic dispersive solid-phase microextraction: A novel approach for the rapid and efficient microextraction of naproxen and ibuprofen employing experimental design with high-performance liquid chromatography.

    PubMed

    Ghorbani, Mahdi; Chamsaz, Mahmoud; Rounaghi, Gholam Hossein

    2016-03-01

    A simple, rapid, and sensitive method for the determination of naproxen and ibuprofen in complex biological and water matrices (cow milk, human urine, river, and well water samples) has been developed using ultrasound-assisted magnetic dispersive solid-phase microextraction. Magnetic ethylendiamine-functionalized graphene oxide nanocomposite was synthesized and used as a novel adsorbent for the microextraction process and showed great adsorptive ability toward these analytes. Different parameters affecting the microextraction were optimized with the aid of the experimental design approach. A Plackett-Burman screening design was used to study the main variables affecting the microextraction process, and the Box-Behnken optimization design was used to optimize the previously selected variables for extraction of naproxen and ibuprofen. The optimized technique provides good repeatability (relative standard deviations of the intraday precision 3.1 and 3.3, interday precision of 5.6 and 6.1%), linearity (0.1-500 and 0.3-650 ng/mL), low limits of detection (0.03 and 0.1 ng/mL), and a high enrichment factor (168 and 146) for naproxen and ibuprofen, respectively. The proposed method can be successfully applied in routine analysis for determination of naproxen and ibuprofen in cow milk, human urine, and real water samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Relative efficacy and tolerability of etoricoxib, celecoxib, and naproxen in the treatment of osteoarthritis : A Bayesian network meta-analysis of randomized controlled trials based on patient withdrawal.

    PubMed

    Song, Gwan Gyu; Seo, Young Ho; Kim, Jae-Hoon; Choi, Sung Jae; Ji, Jong Dae; Lee, Young Ho

    2016-06-01

    This study aimed to assess the relative efficacy and tolerability of etoricoxib, celecoxib, and naproxen at recommended dosages in patients with osteoarthritis (OA). Randomized controlled trials (RCTs) examining the efficacy and tolerability of etoricoxib 30-60 mg, celecoxib 200-400 mg, and naproxen 1000 mg, based on the number of patient withdrawals among those with OA, were included in this network meta-analysis. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs. Eight RCTs, including 5,942 patients, met the inclusion criteria. The proportion of patient withdrawals due to lack of efficacy was significantly lower in the etoricoxib 30-60 mg (OR 0.21, 95 % CrI 0.12-0.38), celecoxib 200-400 mg (OR 0.29, 95 % CrI 0.18-0.47), and naproxen 1000 mg (OR 0.31, 95 % CrI 0.18-0.51) groups than in the placebo group. The number of patient withdrawals due to lack of efficacy tended to be lower in the etoricoxib 30-60 mg group than in the naproxen 1000 mg and celecoxib 200-400 mg groups, although they did not reach statistical significance (OR 0.68, 95 % CrI 0.36-1.33 and OR 0.70, 95 % CrI 0.38-1.37, respectively). Ranking probabilities based on the surface under the cumulative ranking curve (SUCRA) indicated that etoricoxib 30-60 mg had the highest probability of being the best treatment based on the number of withdrawals due to lack of efficacy (SUCRA = 0.9168) followed by celecoxib 200-400 mg (SUCRA = 0.5659), naproxen 1000 mg (SUCRA = 0.5171), and placebo (SUCRA = 0.000189). With respect to tolerability, the number of withdrawals due to adverse events was not significantly different among etoricoxib, celecoxib, naproxen, and placebo, although it tended to be lower with etoricoxib and placebo. Etoricoxib 30-60 mg, celecoxib 200-400 mg, and naproxen 1000 mg were more efficacious than placebo. However, there was no significant difference in efficacy and tolerability between the

  8. Herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide on pharmacokinetic and pharmacodynamic of naproxen in rats.

    PubMed

    Balap, Aishwarya; Lohidasan, Sathiyanarayanan; Sinnathambi, Arulmozhi; Mahadik, Kakasaheb

    2017-01-04

    Andrographis paniculata Nees (Acanthacae) have broad range of pharmacological effects such as hepatoprotective, antifertility, antimalarial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties and is widely used medicinal plant in the traditional Unani and Ayurvedic medicinal systems. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug. To evaluate the pharmacokinetic and pharmacodynamic (anti arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with naproxen (NP) after oral co-administration in wistar rats. After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with NP (7.5mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of C max , t max , t 1/2 , MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity. Co-administration of NP with APE and pure AN decreased systemic exposure level of NP in vivo. The C max , t max, AUC 0-t of NP was decreased. In pharmacodynamic study, NP (10mg/kg) alone and NP+AN (10+60mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups NP+APE, APE and AN alone. The results obtained from this study suggested that NP, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. The knowledge regarding possible herb-drug interaction of NP might be helpful for physicians as well as patients using AP. So further studies should be done to understand the effect of other herbal ingredients of APE on NP as well as to predict the herb-drug interaction in humans

  9. Lysine clonixinate vs naproxen sodium for the acute treatment of migraine: a double-blind, randomized, crossover study.

    PubMed

    Krymchantowski, Abouch Valenty; Peixoto, Patricia; Higashi, Rafael; Silva, Ariovaldo; Schutz, Vivian

    2005-12-14

    The process of inflammation is crucial in migraine, and several nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of migraine attacks. Despite their efficacy, the routine use of NSAIDs is limited by side effects as well as incomplete efficacy in some patients. Among the available options, lysine clonixinate (LC) and naproxen sodium (NS) have proved effective in migraine. The aim of this study was to compare the efficacy and tolerability of oral formulations of LC and NS in the treatment of moderate or severe migraine attacks, with a double-blind, crossover design. Seventy subjects (62 women, 8 men) between ages 18 and 71 years (mean age, 41) with migraine according to the criteria of the International Headache Society were prospectively enrolled. The patients were randomized into 2 groups and each participant treated 2 migraine attacks. Group 1 treated the first attack with LC and the second attack with NS. Group 2 treated 2 attacks in a counterbalanced order. Doses were 250 mg of LC or 550 mg of NS, which were encapsulated for equal appearance. Headache intensity, nausea, photophobia, and side effects were evaluated at baseline, 1 hour, and 2 hours after drug administration. Rescue drugs were allowed after 2 hours for those who didn't respond, and this was also compared between groups. Sixty patients (54 women, 6 men) completed the study. At 1 hour, 13.6% patients who used LC were pain-free compared with 11.9% who used NS (P = .78). At 2 hours, 35.6% patients who took LC and 32.2% who took NS were pain-free (P = .69). At baseline, 52.5% of the patients randomized to group 1 reported nausea, compared with 33.9% in group 2, and both drugs eliminated nausea: At both 1 hour and 2 hours, nausea diminished significantly for those taking LC, but only after 2 hours for those who took NS (P < .0001). Both drugs eliminated photophobia at 1 hour and 2 hours; however, LC was superior to NS in reducing photophobia at 2 hours (P = .027). Ten patients

  10. Novel naproxen/esomeprazole magnesium compound pellets based on acid-independent mechanism: in vitro and in vivo evaluation.

    PubMed

    Lu, Jing; Kan, Shuling; Zhao, Yi; Zhang, Wenli; Liu, Jianping

    2016-09-01

    The purpose of this study was to develop the novel naproxen/esomeprazole magnesium compound pellets (novel-NAP/EMZ) depending on EMZ acid-independent mechanism which has been proved to be predominate in the mechanism of co-therapy with nonsteroidal anti-inflammatory drug. The novel-NAP/EMZ compound pellets, composed of NAP colon-specific pellets (NAP-CSPs) and EMZ modified-release pellets (EMZ-MRPs), were prepared by fluid-bed coating technology with desired in vitro release profiles. The resulting pellets were filled into hard gelatin capsules for in vivo evaluation in rats and compared with the reference compound pellets, consisted of NAP enteric-coated pellets (NAP-ECPs) and EMZ immediate-release pellets (EMZ-IRPs). The reference compound pellets were prepared simulating the drug delivery system of VIMOVO(®). In vivo pharmacokinetics, EMZ-MRPs had significantly larger AUC0-t (p < 0.01), 1.67 times more than that of EMZ-IRPs, and prolonged mean residence time (7.55 ± 0.12 h) than that of IRPs (1.46 ± 0.39 h). NAP-CSPs and NAP-ECPs showed similar AUC0-t. Compared to the reference compound pellets, the novel-NAP/EMZ compound pellets did not show distinct differences in histological mucosal morphology. However, biochemical tests exhibited enhanced total antioxidant capacity, increased nitric oxide content and reduced malondialdehyde level for novel-NAP/EMZ compound pellets, indicating that the acid-independent action took effect. The gastric pH values of novel-NAP/EMZ compound pellets were at a low and stable level, which could ensure normal physiological range of human gastric pH. As a result, the novel-NAP/EMZ compound pellets may be a more suitable formulation with potential advantages by improving bioavailability of drug and further reducing undesirable gastrointestinal damages.

  11. Lysine Clonixinate vs Naproxen Sodium for the Acute Treatment of Migraine: A Double-Blind, Randomized, Crossover Study

    PubMed Central

    Krymchantowski, Abouch Valenty; Peixoto, Patrícia; Higashi, Rafael; Silva, Ariovaldo; Schutz, Vivian

    2005-01-01

    Abstract and Introduction Abstract Background and Objectives The process of inflammation is crucial in migraine, and several nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of migraine attacks. Despite their efficacy, the routine use of NSAIDs is limited by side effects as well as incomplete efficacy in some patients. Among the available options, lysine clonixinate (LC) and naproxen sodium (NS) have proved effective in migraine. The aim of this study was to compare the efficacy and tolerability of oral formulations of LC and NS in the treatment of moderate or severe migraine attacks, with a double-blind, crossover design. Methods Seventy subjects (62 women, 8 men) between ages 18 and 71 years (mean age, 41) with migraine according to the criteria of the International Headache Society were prospectively enrolled. The patients were randomized into 2 groups and each participant treated 2 migraine attacks. Group 1 treated the first attack with LC and the second attack with NS. Group 2 treated 2 attacks in a counterbalanced order. Doses were 250 mg of LC or 550 mg of NS, which were encapsulated for equal appearance. Headache intensity, nausea, photophobia, and side effects were evaluated at baseline, 1 hour, and 2 hours after drug administration. Rescue drugs were allowed after 2 hours for those who didn't respond, and this was also compared between groups. Results Sixty patients (54 women, 6 men) completed the study. At 1 hour, 13.6% patients who used LC were pain-free compared with 11.9% who used NS (P = .78). At 2 hours, 35.6% patients who took LC and 32.2% who took NS were pain-free (P = .69). At baseline, 52.5% of the patients randomized to group 1 reported nausea, compared with 33.9% in group 2, and both drugs eliminated nausea: At both 1 hour and 2 hours, nausea diminished significantly for those taking LC, but only after 2 hours for those who took NS (P < .0001). Both drugs eliminated photophobia at 1 hour and 2 hours; however, LC

  12. Celecoxib or naproxen treatment does not benefit depressive symptoms in persons age 70 and older: findings from a randomized controlled trial.

    PubMed

    Fields, Cynthia; Drye, Lea; Vaidya, Vijay; Lyketsos, Constantine

    2012-06-01

    Several lines of evidence suggest that inflammatory mechanisms may be involved in the severity and progression of depression. One pathway implicated is the production of prostaglandins via the enzyme cyclooxygenase (COX). Although late-life depression in particular has been associated with inflammation, we know of no published studies using COX inhibitors, such as nonsteroidal anti-inflammatory drugs (NSAIDs), in the treatment of depressive syndromes in this population. To evaluate the effect of the NSAIDs celecoxib and naproxen on depressive symptoms in older adults. The Alzheimer's Disease Anti-inflammatory Prevention Trial was a randomized, placebo-controlled, double-masked clinical trial conducted at six U.S. memory clinics. Cognitively normal volunteers age 70 and older with a family history of Alzheimer-like dementia were randomly assigned to receive celecoxib 200 mg twice daily, naproxen sodium 220 mg twice daily, or placebo. The 30-item version of the Geriatric Depression Scale (GDS) was administered to all participants at enrollment and at yearly follow-up visits. Participants with a GDS score greater than 5 at baseline were classified as depressed. Of 2,528 participants enrolled, 2,312 returned for at least one follow-up visit. Approximately one-fifth had significant depressive symptoms at baseline. Mean GDS score, and the percentage with significant depressive symptoms, remained similar over time across all three treatment groups. Furthermore, there was no treatment effect on GDS scores over time in the subgroup of participants with significant depressive symptoms at baseline. In longitudinal analysis using generalized estimating equations (GEE) regression, higher baseline GDS scores, a prior psychiatric history, older age, time in the study, and lower cognition interacting with time, but not treatment assignment, were associated with significantly higher GDS scores over time. Treatment with celecoxib or naproxen did not improve depressive symptoms over

  13. Celecoxib or naproxen treatment does not benefit depressive symptoms in persons aged 70 and over: findings from a randomized controlled trial

    PubMed Central

    Fields, Cynthia; Drye, Lea; Vaidya, Vijay; Lyketsos, Constantine

    2011-01-01

    Background Several lines of evidence suggest that inflammatory mechanisms may be involved in the severity and progression of depression. One pathway implicated is the production of prostaglandins via the enzyme cyclooxygenase (COX). Although late life depression in particular has been associated with inflammation, we know of no published studies using COX inhibitors, such as nonsteroidal anti-inflammatory drugs (NSAIDs), in the treatment of depressive syndromes in this population. Objective To evaluate the effect of the NSAIDs celecoxib and naproxen on depressive symptoms in older adults. Methods The Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT) was a randomized, placebo-controlled, double-masked clinical trial conducted at six U.S. memory clinics. Cognitively normal volunteers aged 70 and over with a family history of Alzheimer-like dementia were randomly assigned to receive celecoxib 200mg BID, naproxen sodium 220mg BID, or placebo. The 30-item version of the Geriatric Depression Scale (GDS) was administered to all participants at enrollment and at yearly follow-up visits. Participants with a GDS score >5 at baseline were classified as depressed. Results Of 2,528 participants enrolled 2,312 returned for at least one follow-up visit. Approximately one-fifth had significant depressive symptoms at baseline. Mean GDS score, and the percentage with significant depressive symptoms, remained similar over time across all three treatment groups. Furthermore, there was no treatment effect on GDS scores over time in the subgroup of participants with significant depressive symptoms at baseline. In longitudinal analysis using Generalized Estimating Equations (GEE) regression, higher baseline GDS scores, a prior psychiatric history, older age, time in the study, and lower cognition interacting with time, but not treatment assignment, were associated with significantly higher GDS scores over time. Conclusions Treatment with celecoxib or naproxen did not

  14. High-speed water impacts of flat plates in different ditching configuration through a Riemann-ALE SPH model

    NASA Astrophysics Data System (ADS)

    Marrone, S.; Colagrossi, A.; Chiron, L.; De Leffe, M.; Le Touzé, D.

    2018-02-01

    The violent water entry of flat plates is investigated using a Riemann-arbitrary Eulerian-Lagrangian (ALE) smoothed particle hydrodynamics (SPH) model. The test conditions are of interest for problems related to aircraft and helicopter emergency landing in water. Three main parameters are considered: the horizontal velocity, the approach angle (i.e., vertical to horizontal velocity ratio) and the pitch angle, α. Regarding the latter, small angles are considered in this study. As described in the theoretical work by Zhao and Faltinsen (1993), for small α a very thin, high-speed jet of water is formed, and the time-spatial gradients of the pressure field are extremely high. These test conditions are very challenging for numerical solvers. In the present study an enhanced SPH model is firstly tested on a purely vertical impact with deadrise angle α = 4°. An in-depth validation against analytical solutions and experimental results is carried out, highlighting the several critical aspects of the numerical modelling of this kind of flow, especially when pressure peaks are to be captured. A discussion on the main difficulties when comparing to model scale experiments is also provided. Then, the more realistic case of a plate with both horizontal and vertical velocity components is discussed and compared to ditching experiments recently carried out at CNR-INSEAN. In the latter case both 2-D and 3-D simulations are considered and the importance of 3-D effects on the pressure peak is discussed for α = 4° and α = 10°.

  15. Comparison of DNA-based techniques for differentiation of production strains of ale and lager brewing yeast.

    PubMed

    Kopecká, J; Němec, M; Matoulková, D

    2016-06-01

    Brewing yeasts are classified into two species-Saccharomyces pastorianus and Saccharomyces cerevisiae. Most of the brewing yeast strains are natural interspecies hybrids typically polyploids and their identification is thus often difficult giving heterogenous results according to the method used. We performed genetic characterization of a set of the brewing yeast strains coming from several yeast culture collections by combination of various DNA-based techniques. The aim of this study was to select a method for species-specific identification of yeast and discrimination of yeast strains according to their technological classification. A group of 40 yeast strains were characterized using PCR-RFLP analysis of ITS-5·8S, NTS, HIS4 and COX2 genes, multiplex PCR, RAPD-PCR of genomic DNA, mtDNA-RFLP and electrophoretic karyotyping. Reliable differentiation of yeast to the species level was achieved by PCR-RFLP of HIS4 gene. Numerical analysis of the obtained RAPD-fingerprints and karyotype revealed species-specific clustering corresponding with the technological classification of the strains. Taxonomic position and partial hybrid nature of strains were verified by multiplex PCR. Differentiation among species using the PCR-RFLP of ITS-5·8S and NTS region was shown to be unreliable. Karyotyping and RFLP of mitochondrial DNA evinced small inaccuracies in strain categorization. PCR-RFLP of HIS4 gene and RAPD-PCR of genomic DNA are reliable and suitable methods for fast identification of yeast strains. RAPD-PCR with primer 21 is a fast and reliable method applicable for differentiation of brewing yeasts with only 35% similarity of fingerprint profile between the two main technological groups (ale and lager) of brewing strains. It was proved that PCR-RFLP method of HIS4 gene enables precise discrimination among three technologically important Saccharomyces species. Differentiation of brewing yeast to the strain level can be achieved using the RAPD-PCR technique. © 2016 The

  16. Inclusion Complexes of a New Family of Non-Ionic Amphiphilic Dendrocalix[4]arene and Poorly Water-Soluble Drugs Naproxen and Ibuprofen.

    PubMed

    Khan, Khalid; Badshah, Syed Lal; Ahmad, Nasir; Rashid, Haroon Ur; Mabkhot, Yahia

    2017-05-11

    The inclusion complexes of a new family of nonionic amphiphilic calix[4]arenes with the anti-inflammatory hydrophobic drugs naproxen (NAP) and ibuprofen (IBP) were investigated. The effects of the alkyl chain's length and the inner core of calix[4]arenes on the interaction of the two drugs with the calix[4]arenes were explored. The inclusion complexes of Amphiphiles 1a - c with NAP and IBP increased the solubility of these drugs in aqueous media. The interaction of 1a - c with the drugs in aqueous media was investigated through fluorescence, molecular modeling, and ¹H-NMR analysis. TEM studies further supported the formation of inclusion complexes. The length of lipophilic alkyl chains and the intrinsic cyclic nature of cailx[4]arene derivatives 1a - c were found to have a significant impact on the solubility of NAP and IBP in pure water.

  17. Novel beta-cyclodextrin derivative functionalized polymethacrylate-based monolithic columns for enantioselective separation of ibuprofen and naproxen enantiomers in capillary electrochromatography.

    PubMed

    Tian, Yun; Zhong, Cheng; Fu, Enqin; Zeng, Zhaorui

    2009-02-06

    A novel enantioselective polymethacrylate-based monolithic column for capillary electrochromatography was prepared by ring-opening reaction of epoxy groups from poly(glycidyl methacrylate-co-ethylene dimethacrylate) monolith with a novel beta-cyclodextrin derivative bearing 4-dimethylamino-1,8-naphthalimide functionalities. Conditions for the ring-opening reaction with respect to different reaction parameters were thoroughly optimized to obtain high electroosmotic flow, separation efficiency and enantioselectivity for the analytes. The nonaqueous mobile phase composition regarding acetonitrile-methanol ratio and the concentration of electrolyte were examined to manipulate the hydrophobic inclusion and anion-exchange interaction between the analytes and chiral stationary phase. It was observed that in addition to beta-cyclodextrin cavity, the electrostatic interaction exhibited pronounced influence on the enantioseparation of acidic analytes. Acidic enantiomers (ibuprofen and naproxen) could be separated with separation factor (alpha) values up to 1.08 and a maximum separation efficiency of 86000 plates/m could be achieved.

  18. A comparative study of the novel spectrophotometric methods versus conventional ones for the simultaneous determination of Esomeprazole magnesium trihydrate and Naproxen in their binary mixture.

    PubMed

    Lotfy, Hayam M; Amer, Sawsan M; Zaazaa, Hala E; Mostafa, Noha S

    2015-01-01

    Two novel simple, specific, accurate and precise spectrophotometric methods manipulating ratio spectra are developed and validated for simultaneous determination of Esomeprazole magnesium trihydrate (ESO) and Naproxen (NAP) namely; absorbance subtraction and ratio difference. The results were compared to that of the conventional spectrophotometric methods namely; dual wavelength and isoabsorptive point coupled with first derivative of ratio spectra and derivative ratio. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for determination of ESO and NAP in their laboratory prepared mixtures and pharmaceutical preparation. No preliminary separation steps are required for the proposed spectrophotometeric procedures. The statistical comparison showed that there is no significant difference between the proposed methods and the reported method with respect to both accuracy and precision. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. The role of sorption and biodegradation in the removal of acetaminophen, carbamazepine, caffeine, naproxen and sulfamethoxazole during soil contact: A kinetics study.

    PubMed

    Martínez-Hernández, Virtudes; Meffe, Raffaella; Herrera López, Sonia; de Bustamante, Irene

    2016-07-15

    In countries like Spain, where water is a limited resource, reusing effluents from wastewater treatment plants may imply the introduction of incompletely eliminated pollutants into the environment. Therefore, this work identified the role of sorption and biodegradation in attenuating pharmaceutical compounds (acetaminophen, carbamazepine, caffeine, naproxen and sulfamethoxazole) in natural soil. It also determined which sorption and removal ("sorption+biodegradation") kinetics models describe the behaviour of these substances in the water-soil system. Presence of potential transformation products (TPs) as a result of pharmaceuticals biodegradation was also studied. To this end, serial batch-type experiments were performed with a soil:water ratio of 1:4 and an initial pharmaceutical concentration of 100μgL(-1). Despite results are dependent on soil characteristics, they revealed that, for those substances with a higher affinity to the soil used (loamy sand), sorption seems to play a key role during the first 48h of contact with soil, and gives way to biodegradation afterwards. The sorption of the pharmaceuticals studied follows a pseudo second-order kinetics. Caffeine and sulfamethoxazole displayed the fastest initial sorption velocities (h=2055 and h=228μgkg(-1)h(-1), respectively). The removal kinetics experiments, satisfactorily simulated by the first-order kinetics model, indicated the presence of potential microbial adaptation to degradation. Indeed, half-lives decreased from 1.6- to 11.7-fold with respect to initial values. The microbial capacity to degrade sulfamethoxazole could be a matter of concern if bacteria have developed resistance to this antibiotic. Caffeine, acetaminophen and sulfamethoxazole were mitigated to a greater extent, whereas the removal of naproxen and carbamazepine was more limited. The appearance of epoxy-carbamazepine and N4-acetyl-sulfamethoxazole as possible TPs of carbamazepine and sulfamethoxazole, respectively, indicated that

  20. Photostability and toxicity of finasteride, diclofenac and naproxen under simulating sunlight exposure: evaluation of the toxicity trend and of the packaging photoprotection

    PubMed Central

    2013-01-01

    Background Drugs photostability plays two different opposite roles; a real advantage arises considering the longer expiration time of the drugs while the consequent persistence in the environment involves an obvious negative effect bound to their harmfulness. On this basis we tested the photostability and toxicity of three pharmaceutical active principles: Finasteride, Diclofenac and Naproxen. The pure active principles, as well as commercial drugs containing them, were considered; for the last, the protective effect of the packaging was also evaluated. Samples were irradiated according to the ICH Guidelines for photostability testing (The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use); a simulating sunlight source (a mercury-vapor lamp coupled to a tungsten filament one) was used to cover the wavelength range 300–2000 nm; Temperature, Relative Humidity, Irradiance and Illuminance were maintained constant during the photodegradation. The concentrations of the pharmaceutical active principles during the photodegradation were monitored by HPLC with UV/Vis detector. Toxicity tests were performed by means of an amperometric biosensor based on suspended yeast cells. Since the products obtained by the photodegradation process can result as toxic or more toxic than the original molecules, tests were performed first and after the photodegadation. Results After 90 hours of exposure the concentration resulted lowered by 42.9%, 88.4% and 91% for Finasteride, Naproxen and Diclofenac respectively. Toxicity of the pure active principles follows the same order of the photostability. After photodegradation a contribute of the reaction products was evidenced. Conclusions The simple and cheap analytical procedure here proposed, allowed to obtain not only data on photostability and toxicity of the pure active principles but, even if roughly, also useful information on the reactions kinetic and toxicity of the

  1. Acylated-naproxen as the surface-active template in the preparation of micro- and nanospherical imprinted xerogels by emulsion techniques.

    PubMed

    Ornelas, Mariana; Azenha, Manuel; Araújo, Maria João; Marques, Eduardo F; Dias-Cabral, A C; Pereira, Carlos; Silva, A Fernando

    2016-03-11

    A strategy based on water-in-oil emulsion for the dispersion of a sol-gel mixture into small droplets was employed with the view of the production of naproxen-imprinted micro- and nanospheres. The procedure, aiming at a surface imprinting process, comprised the synthesis of a naproxen-derived surfactant. The imprinting process occurred at the interface of the emulsions or microemulsions, by the migration of the NAP-surfactant head into the sol-gel drops to leave surficial imprints due mainly to ion-pair interaction with a cationic group contained within the growing sol-gel network. The surface-imprinted microspheric particles exhibited a log-normal size distribution with geometric mean diameter of 3.1μm. A mesoporous texture was found from measurements of the specific surface area (206m(2)/g) and pore diameter (Dp 2nm). Evaluation of the microspheres as packed HPLC stationary phases resulted in the determination of the selectivity factor against ibuprofen (α=2.1), demonstrating the successful imprinting. Chromatographic efficiency, evaluated by the number of theoretical plates (222platescm(-3)), emerged as an outstanding feature among the set of all relatable formats produced before, an advantage intrinsic to the location of the imprinted sites on the surface. The material presented a capacity of 3.2μmolg(-1). Additionally, exploratory work conducted on their nanoscale counterparts resulted in the production of nanospheres in the size order of 10nm providing good indications of a successful imprinting process. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Early and late effects of aspirin and naproxen on microRNAs in the lung and blood of mice, either unexposed or exposed to cigarette smoke

    PubMed Central

    Izzotti, Alberto; Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Longobardi, Mariagrazia; Pulliero, Alessandra; Camoirano, Anna; D'Agostini, Francesco; Geretto, Marta; Micale, Rosanna T.; La Maestra, Sebastiano; Miller, Mark Steven; Steele, Vernon E.; De Flora, Silvio

    2017-01-01

    We recently showed that nonsteroidal anti-inflammatory drugs (NSAIDs) are able to inhibit the lung tumors induced by cigarette smoke, either mainstream (MCS) or environmental (ECS), in female mice. We used subsets of mice to analyze the expression of 1135 microRNAs in both lung and blood serum, as related to the whole-body exposure to smoke and/or oral administration of either aspirin or naproxen. In a first study, we evaluated early microRNA alterations in A/J mice exposed to ECS for 10 weeks, starting at birth, and/or treated with NSAIDs for 6 weeks, starting after weaning. At that time, when no histopathological change were apparent, ECS caused a considerable downregulation of pulmonary microRNAs affecting both adaptive mechanisms and disease-related pathways. Aspirin and naproxen modulated, with intergender differences, the expression of microRNAs having a variety of functions, also including regulation of cyclooxygenases and inflammation. In a second study, we evaluated late microRNA alterations in Swiss H mice exposed to MCS during the first 4 months of life and treated with NSAIDs after weaning until 7.5 months of life, when tumors were detected in mouse lung. Modulation of pulmonary microRNAs by the two NSAIDs was correlated with their ability to prevent preneoplastic lesions (microadenomas) and adenomas in the lung. In both studies, exposure to smoke and/or treatment with NSAIDs also modulated microRNA profiles in the blood serum. However, their levels were poorly correlated with those of pulmonary microRNAs, presumably because circulating microRNAs reflect the contributions from multiple organs and not only from lung. PMID:29156752

  3. Modulation by aspirin and naproxen of nucleotide alterations and tumors in the lung of mice exposed to environmental cigarette smoke since birth

    PubMed Central

    La Maestra, Sebastiano; D’Agostini, Francesco; Izzotti, Alberto; Micale, Rosanna T.; Mastracci, Luca; Camoirano, Anna; Balansky, Roumen; Trosko, James E.; Steele, Vernon E.; De Flora, Silvio

    2015-01-01

    Chemoprevention provides an important strategy for cancer control in passive smokers. Due to the crucial role played by smoke-related chronic inflammation in lung carcinogenesis, of special interest are extensively used pharmacological agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs). We evaluated the ability of aspirin and naproxen, inhibitors of both cyclooxygenase-1 and cyclooxygenase -2, to modulate environmental cigarette smoke (ECS)-induced lung carcinogenesis in A/J mice of both genders. Based on a subchronic toxicity study in 180 postweaning mice, we used 1600mg/kg diet aspirin and 320mg/kg diet naproxen. In the tumor chemoprevention study, using 320 mice, exposure to ECS started soon after birth and administration of NSAIDs started after weaning. At 10 weeks of life, the NSAIDs did not affect the presence of occult blood in feces. As assessed in a subset of 40 mice, bulky DNA adducts and 8-hydroxy-2′-deoxyguanosine levels were considerably increased in ECS-exposed mice and, irrespective of gender, both NSAIDs remarkably inhibited these nucleotide alterations. After exposure for 4 months followed by 5 months in filtered air, ECS induced a significant increase in the yield of surface lung tumors, the 43.7% of which were adenomas and the 56.3% were adenocarcinomas. Oct-4 (octamer-binding transcription factor 4), a marker of cell stemness, was detected in some adenocarcinoma cells. The NAIDs attenuated the yield of lung tumors, but prevention of ECS-induced lung adenomas was statistically significant only in female mice treated with aspirin, which supports a role for estrogens in ECS-related lung carcinogenesis and highlights the antiestrogenic properties of NSAIDs. PMID:26464196

  4. Negative Cooperativity in the Interaction of Prostaglandin H Synthase-1 with the Competitive Inhibitor Naproxen Can Be Described as the Interaction of a Non-competitive Inhibitor with Heterogeneous Enzyme Preparation.

    PubMed

    Filimonov, I S; Berzova, A P; Barkhatov, V I; Krivoshey, A V; Trushkin, N A; Vrzheshch, P V

    2018-02-01

    The kinetic mechanism of the interaction of nonsteroidal anti-inflammatory drugs (NSAIDs) with their main pharmacological target, prostaglandin H synthase (PGHS), has not yet been established. We showed that inhibition of PGHS-1 from sheep vesicular glands by naproxen (a representative of NSAIDs) demonstrates a non-competitive character with respect to arachidonic acid and cannot be described within a framework of the commonly used kinetic schemes. However, it can be described by taking into account the negative cooperativity of naproxen binding to the cyclooxygenase active sites of the PGHS-1 homodimer (the first naproxen molecule forms a more stable complex (K 1 = 0.1 µM) with the enzyme than the second naproxen molecule (K 2 = 9.2 µM)). An apparent non-competitive interaction of PGHS-1 with naproxen is due to slow dissociation of the enzyme-inhibitor complexes. The same experimental data could also be described using commonly accepted kinetic schemes, assuming that naproxen interacts was a mixture of two enzyme species with the inhibition constants K α = 0.05 µM and K β = 18.3 µM. Theoretical analysis and numerical calculations show that the phenomenon of kinetic convergence of these two models has a general nature: when K 2 > K 1 , the kinetic patterns (for transient kinetics and equilibrium state) generated by the cooperative model could be described by a scheme assuming the presence of two enzyme forms with the inhibition constants K α = K 1 /2, K β = 2·K 2 . When K 2 < K 1 , the cooperative model can be presented as a scheme with two inhibitor molecules simultaneously binding to the enzyme with the observed inhibition constant K (K = K 1 ·K 2 ). The assumption on the heterogeneity of the enzyme preparation in relation to its affinity to the inhibitor can be used instead of the assumption on the negative cooperativity of the enzyme-inhibitor interactions for convenient and easy practical description of such phenomena in enzymology, biotechnology

  5. Caractéristiques bactériologiques des infections de liquide de dialyse péritonéale

    PubMed Central

    Jellouli, Manel; Ferjani, Meriem; Abidi, Kamel; Hammi, Yosra; Abdallah, Taieb Ben; Gargah, Tahar

    2015-01-01

    La péritonite infectieuse (PI) est la principale complication de la dialyse péritonéale (DP). L'objectif de notre travail était de déterminer l’écologie bactérienne des PI et d'adapter l'antibiothérapie selon les germes isolés et les résistances observées. Étude rétrospective effectuée chez tous les enfants traités par DP et ayant présenté une PI dans le service de pédiatrie de l'hôpital Charles Nicolle de Tunis (2004-2013). Au total, 61 ont développé 97 PI. L'incidence des PI était de 0,75 épisode/patient-année. La culture du LDP était négative dans 40 cas. Les Gram Positif ont été notés dans 56% des cas avec prédominance du Staphylococcus aureus. Les Gram négatif étaient retrouvés en seconde position (40%) représentés principalement par le Klebsiella pneumoniae et le Pseudomonas aeruginosa. Des souches de Staphylocoque méticilline résistant étaient isolées dans 21,4%. Les bactéries à Gram positif étaient résistantes aux céphalosporines de première génération dans 25% des cas et aucune résistance à la vancomycine n'avait été décelée. Les bactéries à Gram négatif avaient une résistance globale de 38% avec des souches β-lactamase à spectre élargi (BLSE). L'antibiothérapie empirique devra couvrir les germes à Gram positif par la vancomycine et les germes à Gram négatif par la ceftazidime. PMID:26893796

  6. Meditation-related activations are modulated by the practices needed to obtain it and by the expertise: an ALE meta-analysis study

    PubMed Central

    Tomasino, Barbara; Fregona, Sara; Skrap, Miran; Fabbro, Franco

    2013-01-01

    The brain network governing meditation has been studied using a variety of meditation practices and techniques practices eliciting different cognitive processes (e.g., silence, attention to own body, sense of joy, mantras, etc.). It is very possible that different practices of meditation are subserved by largely, if not entirely, disparate brain networks. This assumption was tested by conducting an activation likelihood estimation (ALE) meta-analysis of meditation neuroimaging studies, which assessed 150 activation foci from 24 experiments. Different ALE meta-analyses were carried out. One involved the subsets of studies involving meditation induced through exercising focused attention (FA). The network included clusters bilaterally in the medial gyrus, the left superior parietal lobe, the left insula and the right supramarginal gyrus (SMG). A second analysis addressed the studies involving meditation states induced by chanting or by repetition of words or phrases, known as “mantra.” This type of practice elicited a cluster of activity in the right SMG, the SMA bilaterally and the left postcentral gyrus. Furthermore, the last analyses addressed the effect of meditation experience (i.e., short- vs. long-term meditators). We found that frontal activation was present for short-term, as compared with long-term experience meditators, confirming that experts are better enabled to sustain attentional focus, rather recruiting the right SMG and concentrating on aspects involving disembodiment. PMID:23316154

  7. Sorption and desorption of carbamazepine, naproxen and triclosan in a soil irrigated with raw wastewater: estimation of the sorption parameters by considering the initial mass of the compounds in the soil.

    PubMed

    Durán-Álvarez, Juan C; Prado-Pano, Blanca; Jiménez-Cisneros, Blanca

    2012-06-01

    In conventional sorption studies, the prior presence of contaminants in the soil is not considered when estimating the sorption parameters because this is only a transient state. However, this parameter should be considered in order to avoid the under/overestimation of the soil sorption capacity. In this study, the sorption of naproxen, carbamazepine and triclosan was determined in a wastewater irrigated soil, considering the initial mass of the compounds. Batch sorption-desorption tests were carried out at two soil depths (0-10 cm and 30-40 cm), using either 10 mM CaCl(2) solution or untreated wastewater as the liquid phase. Data were satisfactorily fitted to the initial mass model. For the two soils, release of naproxen and carbamazepine was observed when the CaCl(2) solution was used, but not in the soil/wastewater system. The compounds' release was higher in the topsoil than in the 30-40 cm soil. Sorption coefficients (K(d)) for CaCl(2) solution tests showed that in the topsoil, triclosan (64.9 L kg(-1)) is sorbed to a higher extent than carbamazepine and naproxen (5.81 and 2.39 L kg(-1), respectively). In the 30-40 cm soil, carbamazepine and naproxen K(d) values (11.4 and 4.41 L kg(-1), respectively) were higher than those obtained for the topsoil, while the triclosan K(d) value was significantly lower than in the topsoil (19.2 L kg(-1)). Differences in K(d) values were found when comparing the results obtained for the two liquid phases. Sorption of naproxen and carbamazepine was reversible for both soils, while sorption of triclosan was found to be irreversible. This study shows the sorption behavior of three pharmaceuticals in a wastewater irrigated soil, as well as the importance of considering the initial mass of target pollutants in the estimation of their sorption parameters. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. [Comparative analysis of three treatment regimens for treating gonarthritis with calcitonin, naproxen and flavonoids based on EULAR criteria and visual analogue scale (VAS)].

    PubMed

    Badurski, J; Jeziernicka, E; Naruszewicz, K; Racewicz, A

    1995-11-01

    The newest laboratory and clinical elaborations have described a stimulatory effect of salmon calcitonin (sCT) on cultivated chondrocytes and cartilage explants in regard to their secretory function of glycosaminoglycans, collagen t. II and hyaluonic acid as well as have shown anticatabolic effect of sCT on numerous animal models of osteoarthropathy. Moreover, very few clinical indicated profitable effect of CT on degenerative joint diseases and on rheumatoid arthritis. The aim of the present study is to compare the curative effect of sCT (Miacalcic, Sandoz, nasal spray, 2 x 100 IU/day ) vs flavonoides (VR, Venoruton, Zyma, 2 x 0.6 + Vit. C. 0.2/day) with or without naproxen sodium (AP, Apranax, 2 x 0.550/day) in 30 patients suffering from gonarthritis, treated in 10 months in one of the three regimes: I--(n = 10, BMI-33.3, aged 59.5 y., Larsen gr. -2.5): 1st month-VR, 2 and 3-sCT, 4 and 5-VR, 6 and 7-AP, 8.9 and 10-VR; II--(n = 10, BMI-28.8, aged 56 y., Larsen gr. 2.95): 1st m.-VR, 2 and 3-Ap, 4 and 5-VR, 6 and 7-sCT, 9.9 and 10-VR; III--(n = 10, BMI-31.4, aged 58 y., Larsen gr.-2.8): 1st m.-VR, 2 and 3-sCT, 4 and 5-VR, 6 and 7-sCT, 8.9 and 10-VR. Clinical effects of treatment were evaluated by EULAR criteria, VAS, and the paracetamol consumption. The best results according to all three criteria of improvement have been observed in group III treated only with sCT and VR followed by group I in which sCT was given as the first active drug. This effect lasted until three months after the withdrawal of sCT and/or naproxen. This results supported our opinion on antiosteoarthritic ability of salmon calcitonin and marked curative effect of flavonoides in the treatment of osteoarthritis.

  9. Comparison of large scale purification processes of naproxen enantiomers by chromatography using methanol-water and methanol-supercritical carbon dioxide mobile phases.

    PubMed

    Kamarei, Fahimeh; Vajda, Péter; Guiochon, Georges

    2013-09-20

    This paper compares two methods used for the preparative purification of a mixture of (S)-, and (R)-naproxen on a Whelk-O1 column, using either high performance liquid chromatography or supercritical fluid chromatography. The adsorption properties of both enantiomers were measured by frontal analysis, using methanol-water and methanol-supercritical carbon dioxide mixtures as the mobile phases. The measured adsorption data were modeled, providing the adsorption isotherms and their parameters, which were derived from the nonlinear fit of the isotherm models to the experimental data points. The model used was a Bi-Langmuir isotherm, similar to the model used in many enantiomeric separations. These isotherms were used to calculate the elution profiles of overloaded elution bands, assuming competitive Bi-Langmuir behavior of the two enantiomers. The analysis of these profiles provides the basis for a comparison between supercritical fluid chromatographic and high performance liquid chromatographic preparative scale separations. It permits an illustration of the advantages and disadvantages of these methods and a discussion of their potential performance. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Molecular isotopic engineering (MIE): industrial manufacture of naproxen of predetermined stable carbon-isotopic compositions for authenticity and security protection and intellectual property considerations

    NASA Astrophysics Data System (ADS)

    Jasper, J. P.; Farina, P.; Pearson, A.; Mezes, P. S.; Sabatelli, A. D.

    2016-05-01

    Molecular Isotopic Engineering (MIE) is the directed stable-isotopic synthesis of chemical products for reasons of product identification and of product security, and also for intellectual property considerations. We report here a generally excellent correspondence between the observed and predicted stable carbon-isotopic (δ13C) results for a successful directed synthesis of racemic mixture from its immediate precursors. The observed results are readily explained by the laws of mass balance and isotope mass balance. Oxygen- and hydrogen isotopic results which require an additional assessment of the effects of O and H exchange, presumably due to interaction with water in the reaction solution, are addressed elsewhere. A previous, cooperative study with the US FDA-DPA showed that individual manufacturers of naproxen could readily be differentiated by their stable-isotopic provenance (δ13C, δ18O, and δD ref. 1). We suggest that MIE can be readily employed in the bio/pharmaceutical industry without alteration of present manufacturing processes other than isotopically selecting and/or monitoring reactants and products.

  11. Quality-by-design-based ultra high performance liquid chromatography related substances method development by establishing the proficient design space for sumatriptan and naproxen combination.

    PubMed

    Patel, Prinesh N; Karakam, Vijaya Saradhi; Samanthula, Gananadhamu; Ragampeta, Srinivas

    2015-10-01

    Quality-by-design-based methods hold greater level of confidence for variations and greater success in method transfer. A quality-by-design-based ultra high performance liquid chromatography method was developed for the simultaneous assay of sumatriptan and naproxen along with their related substances. The first screening was performed by fractional factorial design comprising 44 experiments for reversed-phase stationary phases, pH, and organic modifiers. The results of screening design experiments suggested phenyl hexyl column and acetonitrile were the best combination. The method was further optimized for flow rate, temperature, and gradient time by experimental design of 20 experiments and the knowledge space was generated for effect of variable on response (number of peaks ≥ 1.50 - resolution). Proficient design space was generated from knowledge space by applying Monte Carlo simulation to successfully integrate quantitative robustness metrics during optimization stage itself. The final method provided the robust performance which was verified and validated. Final conditions comprised Waters® Acquity phenyl hexyl column with gradient elution using ammonium acetate (pH 4.12, 0.02 M) buffer and acetonitrile at 0.355 mL/min flow rate and 30°C. The developed method separates all 13 analytes within a 15 min run time with fewer experiments compared to the traditional quality-by-testing approach. ©2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Solar photolysis versus TiO2-mediated solar photocatalysis: a kinetic study of the degradation of naproxen and diclofenac in various water matrices.

    PubMed

    Kanakaraju, Devagi; Motti, Cherie A; Glass, Beverley D; Oelgemöller, Michael

    2016-09-01

    Given that drugs and their degradation products are likely to occur as concoctions in wastewater, the degradation of a mixture of two nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac (DCF) and naproxen (NPX), was investigated by solar photolysis and titanium dioxide (TiO2)-mediated solar photocatalysis using an immersion-well photoreactor. An equimolar ratio (1:1) of both NSAIDs in distilled water, drinking water, and river water was subjected to solar degradation. Solar photolysis of the DCF and NPX mixture was competitive particularly in drinking water and river water, as both drugs have the ability to undergo photolysis. However, the addition of TiO2 in the mixture significantly enhanced the degradation rate of both APIs compared to solar photolysis alone. Mineralization, as measured by chemical oxygen demand (COD), was incomplete under all conditions investigated. TiO2-mediated solar photocatalytic degradation of DCF and NPX mixtures produced 15 identifiable degradants corresponding to degradation of the individual NSAIDs, while two degradation products with much higher molecular weight than the parent NSAIDs were identified by liquid chromatography mass spectrometry (LC-MS) and Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS). This study showed that the solar light intensity and the water matrix appear to be the main factors influencing the overall performance of the solar photolysis and TiO2-mediated solar photocatalysis for degradation of DCF and NPX mixtures.

  13. Épidémiologie descriptive de la carcinose péritonéale d’origine digestive à l’Hôpital Universitaire Ibn Rochd de Casablanca (2008-2010)

    PubMed Central

    Benlahfid, Mohammed; Erguibi, Driss; Elhattabi, Khalid; Bensardi, Fatimazahra; Khaiz, Driss; Lafriekh, Rachid; Rebroub, Dounia; Fadil, Abdelaziz; Aboussaouira, Touria

    2017-01-01

    Introduction La carcinose péritonéale est une diffusion inéluctablement terminale chez les patients atteints de cancers abdominaux. C'est le signe d'une maladie avancée ou d'une ré-évolution le plus souvent associée à un pronostic sombre. Environ deux tiers de l'ensemble des carcinoses péritonéales sont d'origine digestive et un tiers d'origine non digestive. Méthodes Il s'agit d'une étude rétrospective descriptive menée entre janvier 2008 et décembre 2010, dans le but de dresser le profil épidémiologique et les facteurs de risques de la carcinose péritonéale d'origine digestive au Centre Hospitalier Universitaire de Casablanca. Résultats Quarante-sept cas de carcinose péritonéale d'origine digestive ont été recensées (22 femmes, 25 hommes) ce qui représente une prévalence de 6.19% et un nombre moyen de 15.6 cas par an. L'âge était le facteur de risque essentiel dans notre série avec un âge moyen de 55.55 ans ±12.32. Les antécédents familiaux présentaient aussi un facteur de risque à prendre en considération. Conclusion A travers notre étude, nous avons conclus que les principaux facteurs de risque de la carcinose péritonéale d'origine digestive au Centre Hospitalier Universitaire Ibn Rochd Casablanca, sont l'âge et les antécédents familiaux. PMID:28979636

  14. Cross-calibrating ALES Envisat and CryoSat-2 Delay-Doppler: A coastal altimetry study in the Indonesian Seas

    NASA Astrophysics Data System (ADS)

    Passaro, Marcello; Dinardo, Salvatore; Quartly, Graham D.; Snaith, Helen M.; Benveniste, Jérôme; Cipollini, Paolo; Lucas, Bruno

    2016-08-01

    A regional cross-calibration between the first Delay-Doppler altimetry dataset from CryoSat-2 and a retracked Envisat dataset is here presented, in order to test the benefits of the Delay-Doppler processing and to expand the Envisat time series in the coastal ocean. The Indonesian Seas are chosen for the calibration, since the availability of altimetry data in this region is particularly beneficial due to the lack of in situ measurements and its importance for global ocean circulation. The Envisat data in the region are retracked with the Adaptive Leading Edge Subwaveform (ALES) retracker, which has been previously validated and applied successfully to coastal sea level research. The study demonstrates that CryoSat-2 is able to decrease the 1-Hz noise of sea level estimations by 0.3 cm within 50 km of the coast, when compared to the ALES-reprocessed Envisat dataset. It also shows that Envisat can be confidently used for detailed oceanographic research after the orbit change of October 2010. Cross-calibration at the crossover points indicates that in the region of study a sea state bias correction equal to 5% of the significant wave height is an acceptable approximation for Delay-Doppler altimetry. The analysis of the joint sea level time series reveals the geographic extent of the semiannual signal caused by Kelvin waves during the monsoon transitions, the larger amplitudes of the annual signal due to the Java Coastal Current and the impact of the strong La Niña event of 2010 on rising sea level trends.

  15. Bioavailability of two oral-tablet and two oral-suspension formulations of naproxen sodium/paracetamol (acetaminophen): single-dose, randomized, open-label, two-period crossover comparisons in healthy Mexican adult subjects.

    PubMed

    Palma-Aguirre, Jose Antonio; Villalpando-Hernández, Jorge; Novoa-Heckel, Germán; Oliva, Iván; Cariño, Lizbeth; López-Bojórquez, Ericka; Burke-Fraga, Victoria; Namur, Salvador; González-de la Parra, Mario

    2009-02-01

    Naproxen sodium/paracetamol (acetaminophen) is a combination for the treatment of symptomatic pain and fever marketed both as a prescription and an over-the-counter product in Mexico. The aim of these 2 studies was to compare the bioavailability and to determine the bioequivalence of 2 test formulations (an oral-tablet formulation containing the combination of naproxen sodium/paracetamol 275/300 mg and an oral-suspension formulation containing the combination of naproxen sodium/paracetamol 375/300 mg per 15 mL) with their corresponding listed reference-drug formulations in Mexico (a list issued by Mexican health authorities). Two separate, single-dose, randomized, open-label, 2-period crossover, postmarketing studies were conducted. For each study, a different set of eligible subjects was selected comprising healthy Mexican adults of either sex, and subjects were randomly assigned to receive 1 test formulation of the combination of naproxen sodium/paracetamol followed by the corresponding reference-drug formulation, or vice versa, with a 1-week washout period between doses. After a 12-hour overnight fast, subjects received a single dose of naproxen sodium/paracetamol 275/300-mg tablet or naproxen sodium/paracetamol 375/300 mg per 15 mL suspension, depending on the study. For the analysis of pharmacokinetic parameters, including C(max), AUC from time 0 (baseline) to 48 hours (AUC(0-48)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline and at 0.16, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours after administration. The formulations were considered bioequivalent if the geometric mean ratios (test/reference) of the C(max) and AUC were within the predetermined range of 80% to 125%. Tolerability was determined by clinical assessment, monitoring vital signs, laboratory analysis results, and subject interviews regarding adverse events. A total of 26 subjects (15 men, 11 women; mean [SD] age, 29 [8] years

  16. A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis.

    PubMed

    Lovell, Daniel J; Dare, Jason A; Francis-Sedlak, Megan; Ball, Julie; LaMoreaux, Brian D; Von Scheven, Emily; Reinhardt, Adam; Jerath, Rita; Alpan, Oral; Gupta, Ramesh; Goldsmith, Donald; Zeft, Andrew; Naddaf, Henry; Gottlieb, Beth; Jung, Lawrence; Holt, Robert J

    2018-06-26

    Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age. JIA is the most common chronic rheumatic disease in children. NSAIDs have been the mainstay of initial management with naproxen (NAP) being commonly used, but they may cause serious side effects such as gastric ulcers which can be reduced by concomitant administration of proton pump inhibitors, such as esomeprazole (ESO). Primary objective was to evaluate the safety and tolerability of 3 fixed doses of NAP/ESO in JIA patients aged 12 to 16 years. Forty-six children and adolescents with JIA by International League of Associations for Rheumatology criteria, mean age of 13.6 years, from 18 US sites were prospectively enrolled over 2 years and followed for up to 6 months. Doses of the NAP/ESO fixed combination were based on baseline weight. The exploratory efficacy outcome was assessed with the ACR Pediatric-30, - 50, - 70, - 90 Response and the Childhood Health Assessment Questionnaire (CHAQ) discomfort and functional scores at months 1, 3, and 6 as change from baseline. Occurrence and causality were assessed for treatment emergent AEs (TEAEs) and discontinuations were monitored monthly. Forty-six patients received at least 1 dose of naproxen/esomeprazole and 36 completed the trial. Thirty-seven (80.4%) had at least 1 treatment emergent adverse event (TEAE) and, with the exception of 2 events in one patient, all of the TEAEs were mild or moderate. Frequent TEAEs (≥5% of patients) were upper respiratory tract and gastrointestinal related. Eleven (23.9%) had at least 1 TEAE considered to be related to study drug. Four patients (8.7%) discontinued due to a TEAE with one of these being the only serious AE reported, acute hepatitis. Mean number of active joints at baseline was 3.1. Improvement in JIA signs and symptoms occurred at most assessments and by month 6, the percentage of patients with an ACR

  17. New spectrophotometric/chemometric assisted methods for the simultaneous determination of imatinib, gemifloxacin, nalbuphine and naproxen in pharmaceutical formulations and human urine

    NASA Astrophysics Data System (ADS)

    Belal, F.; Ibrahim, F.; Sheribah, Z. A.; Alaa, H.

    2018-06-01

    In this paper, novel univariate and multivariate regression methods along with model-updating technique were developed and validated for the simultaneous determination of quaternary mixture of imatinib (IMB), gemifloxacin (GMI), nalbuphine (NLP) and naproxen (NAP). The univariate method is extended derivative ratio (EDR) which depends on measuring every drug in the quaternary mixture by using a ternary mixture of the other three drugs as divisor. Peak amplitudes were measured at 294 nm, 250 nm, 283 nm and 239 nm within linear concentration ranges of 4.0-17.0, 3.0-15.0, 4.0-80.0 and 1.0-6.0 μg mL-1 for IMB, GMI, NLP and NAB, respectively. Multivariate methods adopted are partial least squares (PLS) in original and derivative mode. These models were constructed for simultaneous determination of the studied drugs in the ranges of 4.0-8.0, 3.0-11.0, 10.0-18.0 and 1.0-3.0 μg mL-1 for IMB, GMI, NLP and NAB, respectively, by using eighteen mixtures as a calibration set and seven mixtures as a validation set. The root mean square error of predication (RMSEP) were 0.09 and 0.06 for IMB, 0.14 and 0.13 for GMI, 0.07 and 0.02 for NLP and 0.64 and 0.27 for NAP by PLS in original and derivative mode, respectively. Both models were successfully applied for analysis of IMB, GMI, NLP and NAP in their dosage forms. Updated PLS in derivative mode and EDR were applied for determination of the studied drugs in spiked human urine. The obtained results were statistically compared with those obtained by the reported methods giving a conclusion that there is no significant difference regarding accuracy and precision.

  18. Octadecylamine-Mediated Versatile Coating of CoFe2O4 NPs for the Sustained Release of Anti-Inflammatory Drug Naproxen and in Vivo Target Selectivity.

    PubMed

    Georgiadou, Violetta; Makris, George; Papagiannopoulou, Dionysia; Vourlias, Georgios; Dendrinou-Samara, Catherine

    2016-04-13

    Magnetic nanoparticles (MNPs) can play a distinct role in magnetic drug delivery via their distribution to the targeted area. The preparation of such MNPs is a challenging multiplex task that requires the optimization of size, magnetic, and surface properties for the achievement of desirable target selectivity, along with the sustained drug release as a prerequisite. In that context, CoFe2O4 MNPs with a small size of ∼7 nm and moderate saturation magnetization of ∼60 emu g(-1) were solvothermally synthesized in the presence of octadecylamine (ODA) with a view to investigate the functionalization route effect on the drug release. Synthetic regulations allowed us to prepare MNPs with aminated (AmMNPs) and amine-free (FAmMNPs) surface. The addition of the nonsteroidal anti-inflammatory drug with a carboxylate donor, Naproxen (NAP), was achieved by direct coupling with the NH2 groups, rendered by ODA, through the formation of an amide bond in the case of AmMNPs. In the case of FAmMNPs, indirect coupling of NAP was performed through an intermediate linker (polyethylenimine) and on PEG-ylated MNPs. FT-IR, (1)H NMR, (13)C NMR, and UV-vis data confirmed the addition of NAP, whereas diverse drug-release behavior was observed for the different functionalization approaches. The biological behavior of the MNPs@NAP was evaluated in vitro in rat serum and in vivo in mice, after radiolabeling with a γ-emitting radionuclide, (99m)Tc. The in vivo fate of MNPs@NAP carriers was in straightforward relation with the direct or indirect coupling of NAP. Furthermore, an inflammation was induced intramuscularly, where the directly coupled (99m)Tc-MNPs@NAP carriers showed increased accumulation at the inflammation site.

  19. New spectrophotometric/chemometric assisted methods for the simultaneous determination of imatinib, gemifloxacin, nalbuphine and naproxen in pharmaceutical formulations and human urine.

    PubMed

    Belal, F; Ibrahim, F; Sheribah, Z A; Alaa, H

    2018-06-05

    In this paper, novel univariate and multivariate regression methods along with model-updating technique were developed and validated for the simultaneous determination of quaternary mixture of imatinib (IMB), gemifloxacin (GMI), nalbuphine (NLP) and naproxen (NAP). The univariate method is extended derivative ratio (EDR) which depends on measuring every drug in the quaternary mixture by using a ternary mixture of the other three drugs as divisor. Peak amplitudes were measured at 294nm, 250nm, 283nm and 239nm within linear concentration ranges of 4.0-17.0, 3.0-15.0, 4.0-80.0 and 1.0-6.0μgmL -1 for IMB, GMI, NLP and NAB, respectively. Multivariate methods adopted are partial least squares (PLS) in original and derivative mode. These models were constructed for simultaneous determination of the studied drugs in the ranges of 4.0-8.0, 3.0-11.0, 10.0-18.0 and 1.0-3.0μgmL -1 for IMB, GMI, NLP and NAB, respectively, by using eighteen mixtures as a calibration set and seven mixtures as a validation set. The root mean square error of predication (RMSEP) were 0.09 and 0.06 for IMB, 0.14 and 0.13 for GMI, 0.07 and 0.02 for NLP and 0.64 and 0.27 for NAP by PLS in original and derivative mode, respectively. Both models were successfully applied for analysis of IMB, GMI, NLP and NAP in their dosage forms. Updated PLS in derivative mode and EDR were applied for determination of the studied drugs in spiked human urine. The obtained results were statistically compared with those obtained by the reported methods giving a conclusion that there is no significant difference regarding accuracy and precision. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Prevention of Chemically-Induced Urinary Bladder Cancers by Naproxen: Protocols to Reduce Gastric Toxicity in Humans Do Not Alter Preventive Efficacy

    PubMed Central

    Lubet, Ronald A.; Scheiman, James M.; Bode, Ann; White, Jonathan; Minasian, Lori; Juliana, M. Margaret; Boring, Daniel L.; Steele, Vernon E.; Grubbs, Clinton J.

    2015-01-01

    The COX inhibitors (NSAIDs/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2 specific inhibitors have progressed to clinical trials, and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular (CV) effects. Certain NSAIDs (e.g., naproxen (NPX)] have a good cardiac profile, but can cause gastric toxicity. The present studies examined protocols to reduce this toxicity of NPX. Female Fischer-344 rats were treated weekly with the urinary bladder specific carcinogen hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with NPX (40 mg/Kg BW/day, gavage) or with the proton pump inhibitor omeprazole (4.0 mg/Kg BW/day) either singly or in combination beginning 2 weeks after the final OH-BBN. OH-BBN treated rats, 96% developed urinary bladder cancers. While omeprazole alone was ineffective (97% cancers), NPX alone or combined with omeprazole prevented cancers; yielding 27 and 35% cancers, respectively. In a separate study, OH-BBN treated rats were administered NPX: (A) daily, (B) 1 week daily NPX/1wk vehicle, (C) 3 weeks daily NPX/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN treatment. In the intermittent dosing study, protocol A, B, C and D resulted in palpable cancers in 27%, 22%, 19% and 96% of rats (P<0.01). Short-term NPX treatment increased apoptosis, but did not alter proliferation in the urinary bladder cancers. Two different protocols which should decrease the gastric toxicity of NSAIDs in humans did not alter chemopreventive efficacy. This should encourage the use of NSAIDs (e.g. NPX) in clinical prevention trials. PMID:25762530

  1. Double-blind, randomized, double-dummy clinical trial comparing the efficacy of ketorolac trometamol and naproxen for acute low back pain.

    PubMed

    Plapler, Pérola Grinberg; Scheinberg, Morton Aaron; Ecclissato, Christina da Cunha; Bocchi de Oliveira, Monalisa Fernanda; Amazonas, Roberto Bleuel

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common type of medication used in the treatment of acute pain. Ketorolac trometamol (KT) is a nonnarcotic, peripherally acting nonsteroidal anti-inflammatory drug with analgesic effects comparable to certain opioids. The aim of this study was to compare the efficacy of KT and naproxen (NA) in the treatment of acute low back pain (LBP) of moderate-to-severe intensity. In this 10-day, Phase III, randomized, double-blind, double-dummy, noninferiority trial, participants with acute LBP of moderate-to-severe intensity as determined through a visual analog scale (VAS) were randomly assigned in a 1:1 ratio to receive sublingual KT 10 mg three times daily or oral NA 250 mg three times daily. From the second to the fifth day of treatment, if patient had VAS >40 mm, increased dosage to four times per day was allowed. The primary end point was the reduction in LBP as measured by VAS. We also performed a post hoc superiority analysis. KT was not inferior to NA for the reduction in LBP over 5 days of use as measured by VAS scores (P=0.608 for equality of variance; P=0.321 for equality of means) and by the Roland-Morris Disability Questionnaire (P=0.180 for equality of variance test; P=0.446 for equality of means) using 95% confidence intervals. The percentage of participants with improved pain relief 60 minutes after receiving the first dose was higher in the KT group (24.2%) than in the NA group (6.5%; P=0.049). The most common adverse effects were heartburn, nausea, and vomiting. KT is not inferior in efficacy and delivers faster pain relief than NA.

  2. Double-blind, randomized, double-dummy clinical trial comparing the efficacy of ketorolac trometamol and naproxen for acute low back pain

    PubMed Central

    Plapler, Pérola Grinberg; Scheinberg, Morton Aaron; Ecclissato, Christina da Cunha; Bocchi de Oliveira, Monalisa Fernanda; Amazonas, Roberto Bleuel

    2016-01-01

    Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common type of medication used in the treatment of acute pain. Ketorolac trometamol (KT) is a nonnarcotic, peripherally acting nonsteroidal anti-inflammatory drug with analgesic effects comparable to certain opioids. Objective The aim of this study was to compare the efficacy of KT and naproxen (NA) in the treatment of acute low back pain (LBP) of moderate-to-severe intensity. Patients and methods In this 10-day, Phase III, randomized, double-blind, double-dummy, noninferiority trial, participants with acute LBP of moderate-to-severe intensity as determined through a visual analog scale (VAS) were randomly assigned in a 1:1 ratio to receive sublingual KT 10 mg three times daily or oral NA 250 mg three times daily. From the second to the fifth day of treatment, if patient had VAS >40 mm, increased dosage to four times per day was allowed. The primary end point was the reduction in LBP as measured by VAS. We also performed a post hoc superiority analysis. Results KT was not inferior to NA for the reduction in LBP over 5 days of use as measured by VAS scores (P=0.608 for equality of variance; P=0.321 for equality of means) and by the Roland–Morris Disability Questionnaire (P=0.180 for equality of variance test; P=0.446 for equality of means) using 95% confidence intervals. The percentage of participants with improved pain relief 60 minutes after receiving the first dose was higher in the KT group (24.2%) than in the NA group (6.5%; P=0.049). The most common adverse effects were heartburn, nausea, and vomiting. Conclusion KT is not inferior in efficacy and delivers faster pain relief than NA. PMID:27382251

  3. Anoplastie périnéale simple pour le traitement des malformations anorectales basses chez l'adulte, à propos de deux cas

    PubMed Central

    Echchaoui, Abdelmoughit; Benyachou, Malika; Hafidi, Jawad; Fathi, Nahed; Mohammadine, Elhamid; ELmazouz, Samir; Gharib, Nour-eddine; Abbassi, Abdellah

    2014-01-01

    Les malformations anorectales chez l'adulte sont des anomalies congénitales rares du tube digestif qui prédominent chez le sexe féminin. Notre étude porte sur deux observations de malformation anorectale basses vues et traitées au stade adulte par les 2 équipes (plasticiens et viscéralistes) à l'Hôpital Avicenne à Rabat. Il s'agit d'un homme de 24 ans avec une dyschésie anale l'autre cas est une femme de 18 ans avec une malformation anovulvaire Les caractéristiques cliniques combinées avec les imageries radiologiques (lavement baryté, et la manométrie anorectale) ont confirmé qu'il s'agit d'une malfomation anorectale basse. Les deux cas sont corrigés par une reconstruction sphinctérienne, réimplantation anale avec anoplastie périnéale. Les suites opératoires étaient simples, pas de souffrance cutanée ou nécrose, avec changement de pansement gras chaque jour. Le résultat fonctionnel (la continence) était favorable pour les 2 patients. La présentation des MAR à l’âge adulte est rare, d’étiologie mal connu, elles apparaissent selon le mode sporadique. Les caractéristiques cliniques, couplées à l'imagerie (lavement baryté, IRM pelvienne), l'endoscopie et la manométrie anorectale, permettent de confirmer le diagnostic et classer ces anomalies en 3 types: basses, intermédiaires, et hautes. Les formes basses sont traités d'emblée par une réimplantation anale et anoplastie périnéale simple tels nos deux cas, elles peuvent être traités dans certains cas par un abaissement anorectale associé à une plastie V-Y permettant ainsi un emplacement anatomique correct de l'anus; alors que les formes hautes ou intermédiaires relèvent d'une chirurgie complexe avec souvent une dérivation digestive transitoire. Contrairement aux autres formes, Les formes basses ont un pronostic fonctionnel favorable. PMID:25667689

  4. Gene distribution of ABO blood type system on the Dengue Hemorrhagic Fever (DHF) patients in the working area of Puskesmas Bonto Bangun, District of Rilau Ale, Bulukumba

    NASA Astrophysics Data System (ADS)

    Sjafaraenan; Alvionita, D. N.; Agus, R.; Sabran, A.

    2018-03-01

    This research is about gene distribution of ABO blood type system on the Dengue Hemorrhagic Fever (DHF) patients in the working area of Puskesmas Bonto Bangun, District of Rilau Ale, Bulukumba. This research aimed to determine the blood type which is most affected by DHF using ABO blood type system. In this research, there are 104 samples, 8 of them were attacked by DF and 96 were attacked by DHF. From the 96 patients of DHF, there were 38 patients with A-blood type, 17 patients with B-blood type, 36 patients with O-blood type and 5 patients of AB-blood type. The data were tested using genotype frequency test and the results showed that the percentage of A-homozygous blood type (IAIA) is 0:09%; A heterozygous blood type (IAIo) is 0:36%; B-homozygous blood type (IBIB) is 0.01%; B heterozygous blood type (IB Io) is 0.12%; AB blood type (IAIB) is 0.06% and O blood type (IoIo) is 12:36%. So the biggest frequency of genotype are IAIo (0.36%) and IoIo (0.36%). The results showed that O blood type gene is the most affected by DHF. Then continued by the regression test between blood type and DHF, it is obtained that the correlation value is 1 which indicated that there is a strong relationship.

  5. Estimating eruption temperature from thermal emission spectra of lava fountain activity in the Erta'Ale (Ethiopia) volcano lava lake: Implications for observing Io's volcanoes

    USGS Publications Warehouse

    Davies, Ashley G.; Keszthelyi, Laszlo P.; McEwen, Alfred S.

    2011-01-01

    We have analysed high-spatial-resolution and high-temporal-resolution temperature measurements of the active lava lake at Erta'Ale volcano, Ethiopia, to derive requirements for measuring eruption temperatures at Io's volcanoes. Lava lakes are particularly attractive targets because they are persistent in activity and large, often with ongoing lava fountain activity that exposes lava at near-eruption temperature. Using infrared thermography, we find that extracting useful temperature estimates from remote-sensing data requires (a) high spatial resolution to isolate lava fountains from adjacent cooler lava and (b) rapid acquisition of multi-color data. Because existing spacecraft data of Io's volcanoes do not meet these criteria, it is particularly important to design future instruments so that they will be able to collect such data. Near-simultaneous data at more than two relatively short wavelengths (shorter than 1 μm) are needed to constrain eruption temperatures. Resolving parts of the lava lake or fountains that are near the eruption temperature is also essential, and we provide a rough estimate of the required image scale.

  6. Estimating eruption temperature from thermal emission spectra of lava fountain activity in the Erta'Ale (Ethiopia) volcano lava lake: Implications for observing Io's volcanoes

    USGS Publications Warehouse

    Davies, A.G.; Keszthelyi, L.; McEwen, A.S.

    2011-01-01

    We have analysed high-spatial-resolution and high-temporal-resolution temperature measurements of the active lava lake at Erta'Ale volcano, Ethiopia, to derive requirements for measuring eruption temperatures at Io's volcanoes. Lava lakes are particularly attractive targets because they are persistent in activity and large, often with ongoing lava fountain activity that exposes lava at near-eruption temperature. Using infrared thermography, we find that extracting useful temperature estimates from remote-sensing data requires (a) high spatial resolution to isolate lava fountains from adjacent cooler lava and (b) rapid acquisition of multi-color data. Because existing spacecraft data of Io's volcanoes do not meet these criteria, it is particularly important to design future instruments so that they will be able to collect such data. Near-simultaneous data at more than two relatively short wavelengths (shorter than 1 ??m) are needed to constrain eruption temperatures. Resolving parts of the lava lake or fountains that are near the eruption temperature is also essential, and we provide a rough estimate of the required image scale. ?? 2011 by the American Geophysical Union.

  7. A coordinate-based ALE functional MRI meta-analysis of brain activation during verbal fluency tasks in healthy control subjects

    PubMed Central

    2014-01-01

    Background The processing of verbal fluency tasks relies on the coordinated activity of a number of brain areas, particularly in the frontal and temporal lobes of the left hemisphere. Recent studies using functional magnetic resonance imaging (fMRI) to study the neural networks subserving verbal fluency functions have yielded divergent results especially with respect to a parcellation of the inferior frontal gyrus for phonemic and semantic verbal fluency. We conducted a coordinate-based activation likelihood estimation (ALE) meta-analysis on brain activation during the processing of phonemic and semantic verbal fluency tasks involving 28 individual studies with 490 healthy volunteers. Results For phonemic as well as for semantic verbal fluency, the most prominent clusters of brain activation were found in the left inferior/middle frontal gyrus (LIFG/MIFG) and the anterior cingulate gyrus. BA 44 was only involved in the processing of phonemic verbal fluency tasks, BA 45 and 47 in the processing of phonemic and semantic fluency tasks. Conclusions Our comparison of brain activation during the execution of either phonemic or semantic verbal fluency tasks revealed evidence for spatially different activation in BA 44, but not other regions of the LIFG/LMFG (BA 9, 45, 47) during phonemic and semantic verbal fluency processing. PMID:24456150

  8. [Endproducts and receptors of advanced glycation and lipoxidation (AGE, ALE, RAGE) and chronic diseases from the perspective of food and nutrition].

    PubMed

    Stig, Bengmark; Hajdú, Nóra

    2008-04-27

    Chronic diseases as well as complications to acute and chronic disease are repeatedly associated with accumulation in the body of glycated and lipoxidated proteins and peptides. These molecules are strongly associated with activation of a specific receptor called RAGE and a long-lasting exaggerated level of inflammation in the body. PubMed reports in excess of 5000 papers plus about 14000 articles about the related HbA 1c , most of them published in the last five years. Most of available abstracts have been read and circa 800 full papers studied in detail. RAGE, a member of the immunoglobulin superfamily of cell surface molecules and receptor for advanced glycation endproducts, functions as a master switch, induces sustained activation of NF-kappaB, suppresses a series of endogenous autoregulatory functions and converts long-lasting pro-inflammatory signals into sustained cellular dysfunction and disease. Its activation is associated with high levels of dysfunctioning proteins in body fluids and tissues, and strongly associated with a series of diseases from allergy and Alzheimer to rheumatoid arthritis and urogenital disorders. Heat-treatment, irradiation and ionisation of foods increase the content in foods of AGE/ALE. Some processed foods are much like tobacco smoking great contributors to accumulation of glycated and lipoxidated molecules in the tissues. Change of life style: avoidance of foods rich in deranged proteins and peptides and increased consumption of antioxidants, especially polyphenols counteracts such a development.

  9. L'endométriose périnéale profonde sur cicatrice d’épisiotomie: à propos d'un cas rare

    PubMed Central

    Laadioui, Meriem; Alaoui, Fdili; Jayi, Sofia; Bouguern, Hakima; Chaara, Hikmat; Melhouf, Moulay Aabdelilah

    2013-01-01

    Parmi les localisations rares de l'endométriose sur cicatrice, celle du périnée demeure exceptionnelle, l'origine en est souvent iatrogène (épisiotomie). Nous rapportons le cas d'une patiente présentant une douleur cyclique, au niveau de la cicatrice d’épisiotomie. Avec à l'examen clinique une masse de 3,5 cm de grand diamètre au niveau de la cicatrice d’épisiotomie. L’écho périnéale a objectivé une image hypoéchgène hétérogène non vascularisée en regard de la cicatrice d’épisiotomie faisant 3,23/1cm. L'excision de la lésion a été réalisée et l’étude anatomopathologique a confirmé le diagnostic d'endométriose. Les suites postopératoires étaient simples avec un recul de 3 mois sans récidive de la douleur ni de la masse. A travers notre cas et une revue de la littérature, nous insistons sur les la nécessité du diagnostic clinique et d'une prise en charge précoce en vue d'améliorer le pronostic de cette entité rare. PMID:24778749

  10. Gastrointestinal safety of celecoxib versus naproxen in patients with cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding (CONCERN): an industry-independent, double-blind, double-dummy, randomised trial.

    PubMed

    Chan, Francis K L; Ching, Jessica Y L; Tse, Yee Kit; Lam, Kelvin; Wong, Grace L H; Ng, Siew C; Lee, Vivian; Au, Kim W L; Cheong, Pui Kuan; Suen, Bing Y; Chan, Heyson; Kee, Ka Man; Lo, Angeline; Wong, Vincent W S; Wu, Justin C Y; Kyaw, Moe H

    2017-06-17

    Present guidelines are conflicting for patients at high risk of both cardiovascular and gastrointestinal events who continue to require non-steroidal anti-inflammatory drugs (NSAIDs). We hypothesised that a cyclooxygenase-2-selective NSAID plus proton-pump inhibitor is superior to a non-selective NSAID plus proton-pump inhibitor for prevention of recurrent ulcer bleeding in concomitant users of aspirin with previous ulcer bleeding. For this industry-independent, double-blind, double-dummy, randomised trial done in one academic hospital in Hong Kong, we screened patients with arthritis and cardiothrombotic diseases who were presenting with upper gastrointestinal bleeding, were on NSAIDs, and require concomitant aspirin. After ulcer healing, an independent staff member randomly assigned (1:1) patients who were negative for Helicobacter pylori with a computer-generated list of random numbers to receive oral administrations of either celecoxib 100 mg twice per day plus esomeprazole 20 mg once per day or naproxen 500 mg twice per day plus esomeprazole 20 mg once per day for 18 months. All patients resumed aspirin 80 mg once per day. Both patients and investigators were masked to their treatments. The primary endpoint was recurrent upper gastrointestinal bleeding within 18 months. The primary endpoint and secondary safety endpoints were analysed in the modified intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT00153660. Between May 24, 2005, and Nov 28, 2012, we enrolled 514 patients, assigning 257 patients to each study group, all of whom were included in the intention-to-treat population. Recurrent upper gastrointestinal bleeding occurred in 14 patients in the celecoxib group (nine gastric ulcers and five duodenal ulcers) and 31 patients in the naproxen group (25 gastric ulcers, three duodenal ulcers, one gastric ulcer and duodenal ulcer, and two bleeding erosions). The cumulative incidence of recurrent bleeding in 18 months

  11. Comparison of Clinical Efficacies of Preoperatively Initiated Naproxen Sodium-Codeine Phosphate in Combination, Diclofenac Potassium, and Benzydamine Hydrochloride for Pain, Edema, and Trismus After Extraction of Impacted Lower Third Molar: A Randomized Double-Blind Study.

    PubMed

    Cigerim, Levent; Eroglu, Cennet Neslihan

    2018-03-01

    The aim of this study was to compare the clinical efficacies of naproxen sodium-codeine phosphate in combination, benzydamine hydrochloride, and diclofenac potassium for pain, edema, and trismus after lower third molar extraction. Ninety healthy volunteers in whom impacted third molar extraction was indicated were randomly distributed into 3 groups. One hour before the tooth-extraction process, patients were administered one of the following drugs: naproxen sodium, 550 mg, and codeine phosphate, 30 mg, in a tablet; diclofenac potassium, 50 mg, in a coated pill; or benzydamine hydrochloride, 50 mg, in a coated pill. Pain assessment was conducted via a visual analog scale; edema assessment, by measuring the distances between predetermined facial landmarks; and trismus assessment, by measuring interincisal distance. Regarding rescue analgesics (paracetamol, 500 mg), the number and time of use by patients were recorded. Naproxen sodium-codeine phosphate was more effective for pain, edema, and trismus than diclofenac potassium and benzydamine hydrochloride (P < .05). Benzydamine hydrochloride yielded similar clinical responses to diclofenac potassium (P > .05). No drug-related side effects were observed. Naproxen sodium-codeine phosphate constitutes the drug of choice after the extraction of a patient's impacted lower third molar. Benzydamine hydrochloride has similar efficacy to diclofenac potassium, and it can be used as a nonsteroidal anti-inflammatory analgesic drug. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Stability of Allopurinol, Amitriptyline Hydrochloride, Carbamazepine, Domperidone, Isoniazid, Ketoconazole, Lisinopril, Naproxen, Paracetamol (Acetaminophen), and Sertraline Hydrochloride in SyrSpend SF PH4 Oral Suspensions.

    PubMed

    Polonini, Hudson C; Loures, Sharlene; de Araujo, Edson Peter; Brandão, Marcos Antônio F; Ferreira, Anderson O

    2016-01-01

    Oral liquids are safe alternatives to solid dosage forms, notably for elderly and pediatric patients that present dysphagia. The use of ready-to-use suspending vehicles such as SyrSpend SF PH4 is a suitable resource for pharmacists as they constitute a safe and timesaving option that has been studied often. The objective of this study was to evaluate the stability of 10 commonly used active pharmaceutical ingredients (allopurinol 20 mg/mL; amitriptyline hydrochloride 10 mg/mL; carbamazepine 25 mg/mL; domperidone 5 mg/mL; isoniazid 10 mg/mL; ketoconazole 20 mg/mL; lisinopril 1 mg/mL; naproxen 25 mg/mL; paracetamol [acetaminophen] 50 mg/mL; and sertraline hydrochloride 10 mg/mL) compounded in oral suspensions using SyrSpend SF PH4 as the vehicle throughout the study period and stored both at controlled refrigerated (2°C to 8°C) and room temperature (20°C to 25°C). Stability was assessed by means of measuring the percent recovery at varying time points throughout a 90-day period. The quantification of the active pharmaceutical ingredients was performed by high-performance liquid chromatography through a stability-indicating method. Methods were adequately validated. Forced-degradation studies showed that at least one parameter influenced the stability of the active pharmaceutical ingredients. All suspensions were assayed and showed active pharmaceutical ingredient contents between 90% and 110% during the 90-day study period. Although the forced-degradation experiments led to visible fluctuations in the chromatographic responses, the final preparations were stable in the storage conditions. The beyond-use dates of the preparations were found to be at least 90 days for all suspensions, both for controlled refrigerated temperature and room temperature. This confirms that SyrSpend SF PH4 is a stable suspending vehicle for compounding with a broad range of different active pharmaceutical ingredients for different medical usages. Copyright© by International Journal of

  13. Druggists and pharmacists as gatekeepers: sales routines and compliance with sales protocols for over-the-counter naproxen 275 mg medicines in the Netherlands.

    PubMed

    van Hoof, Joris J; Cents, Michel H G; Megens, Nicole M J; van der Tang, Sijbrand J

    2014-09-01

    Since for the sales of over-the-counter (OTC) medicines, prescribing physicians are not involved, and written instructions on/in the medicine boxes are inefficient, druggists and pharmacists are important gatekeepers in preventing customers' accidents. In this study we investigated the sales routines, and compliance with sales protocols, in order to evaluate that gatekeeper's function. By means of the mystery shopping method, 228 pharmacies and drugstores in The Netherlands were visited and a naproxen 275mg medium-risk medicine was requested for a (fictitious) patient who was suffering from severe back pains. According to the sales protocols the vendors should never sell the requested medicine, because the mystery shoppers only gave an answer to one of the four mandatory sales protocol questions. Furthermore, the requested medicine is not the right or best choice for back pains. Four different scenarios were used in a 2×2 design (8-year-old patient vs. 25-year-old patient, and 1 box with 12 pills vs. 3 boxes with 12 pills). Of the drugstores and pharmacies only 16.7% complied with the sales protocols and did not sell the specific (or comparable) medicine, after asking all four mandatory questions (or already after one, two or three questions). Most vendors (83.3%) did not comply and sold the requested medicine, a comparable medicine, or even a more risky medicine after no question at all (or after asking some or even all four questions). Although both score low, pharmacists show better compliance (23.9%) than druggists (10.1%). When it comes to OTC medicines, druggists and pharmacists largely commit sloppy sales. The expected gatekeeping function of pharmacists and druggists is very limited, and customers might be in danger of inappropriate medicine selection, quantity and usage. We call for thorough evaluation of the over-the-counter system, improvement of the educational programs for medicine providers, and national campaigns to inform the public. Copyright

  14. An interpolation-free ALE scheme for unsteady inviscid flows computations with large boundary displacements over three-dimensional adaptive grids

    NASA Astrophysics Data System (ADS)

    Re, B.; Dobrzynski, C.; Guardone, A.

    2017-07-01

    A novel strategy to solve the finite volume discretization of the unsteady Euler equations within the Arbitrary Lagrangian-Eulerian framework over tetrahedral adaptive grids is proposed. The volume changes due to local mesh adaptation are treated as continuous deformations of the finite volumes and they are taken into account by adding fictitious numerical fluxes to the governing equation. This peculiar interpretation enables to avoid any explicit interpolation of the solution between different grids and to compute grid velocities so that the Geometric Conservation Law is automatically fulfilled also for connectivity changes. The solution on the new grid is obtained through standard ALE techniques, thus preserving the underlying scheme properties, such as conservativeness, stability and monotonicity. The adaptation procedure includes node insertion, node deletion, edge swapping and points relocation and it is exploited both to enhance grid quality after the boundary movement and to modify the grid spacing to increase solution accuracy. The presented approach is assessed by three-dimensional simulations of steady and unsteady flow fields. The capability of dealing with large boundary displacements is demonstrated by computing the flow around the translating infinite- and finite-span NACA 0012 wing moving through the domain at the flight speed. The proposed adaptive scheme is applied also to the simulation of a pitching infinite-span wing, where the bi-dimensional character of the flow is well reproduced despite the three-dimensional unstructured grid. Finally, the scheme is exploited in a piston-induced shock-tube problem to take into account simultaneously the large deformation of the domain and the shock wave. In all tests, mesh adaptation plays a crucial role.

  15. What you see is what you eat: an ALE meta-analysis of the neural correlates of food viewing in children and adolescents.

    PubMed

    van Meer, Floor; van der Laan, Laura N; Adan, Roger A H; Viergever, Max A; Smeets, Paul A M

    2015-01-01

    Food cues are omnipresent and may enhance overconsumption. In the last two decades the prevalence of childhood obesity has increased dramatically all over the world, largely due to overconsumption. Understanding children's neural responses to food may help to develop better interventions for preventing or reducing overconsumption. We aimed to determine which brain regions are concurrently activated in children/adolescents in response to viewing food pictures, and how these relate to adult findings. Two activation likelihood estimation (ALE) meta-analyses were performed: one with studies in normal weight children/adolescents (aged 8-18, 8 studies, 137 foci) and one with studies in normal weight adults (aged 18-45, 16 studies, 178 foci). A contrast analysis was performed for children/adolescents vs. adults. In children/adolescents, the most concurrent clusters were in the left lateral orbitofrontal cortex (OFC), the bilateral fusiform gyrus, and the right superior parietal lobule. In adults, clusters in similar areas were found. Although the number of studies for a direct statistical comparison between the groups was relatively low, there were indications that children/adolescents may not activate areas important for cognitive control. Overall, the number of studies that contributed to the significant clusters was moderate (6-75%). In summary, the brain areas most consistently activated in children/adolescents by food viewing are part of the appetitive brain network and overlap with those found in adults. However, the age range of the children studied was rather broad. This study offers important recommendations for future research; studies making a direct comparison between adults and children in a sufficiently narrow age range would further elucidate how neural responses to food cues change during development. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Chemiluminescence of the reaction system Ce(IV)-non-steroidal anti-inflammatory drugs containing europium(III) ions and its application to the determination of naproxen in pharmaceutical preparations and urine.

    PubMed

    Kaczmarek, Małgorzata

    2011-11-01

    The chemiluminescence (CL) of oxidation of non-steroidal anti-inflammatory drugs (NSAIDs) by Ce(IV) ions, was recorded in the presence and absence europium(III) ions, in solution of pH ~ 4 of solution. Kinetic curves and CL emission spectra of the all studied systems were discussed. CL of measurable intensity was observed in the Ce(IV)-NP-Eu(III) reaction system only in acidic solutions. The CL spectrum rcegistered for this system shows emission bands, typical of Eu(III) ions, with maximum at λ ~ 600 nm. The chemiluminescent method, based on Eu(III) emission in reaction system of NP-Ce(IV)-Eu(III) in acid solution was therefore used for the determination of naproxen in mixture of non-steroidal anti-inflammatory drugs.

  17. Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: the AleCardio randomized clinical trial.

    PubMed

    Lincoff, A Michael; Tardif, Jean-Claude; Schwartz, Gregory G; Nicholls, Stephen J; Rydén, Lars; Neal, Bruce; Malmberg, Klas; Wedel, Hans; Buse, John B; Henry, Robert R; Weichert, Arlette; Cannata, Ruth; Svensson, Anders; Volz, Dietmar; Grobbee, Diederick E

    2014-04-16

    No therapy directed against diabetes has been shown to unequivocally reduce the excess risk of cardiovascular complications. Aleglitazar is a dual agonist of peroxisome proliferator-activated receptors with insulin-sensitizing and glucose-lowering actions and favorable effects on lipid profiles. To determine whether the addition of aleglitazar to standard medical therapy reduces cardiovascular morbidity and mortality among patients with type 2 diabetes mellitus and a recent acute coronary syndrome (ACS). AleCardio was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial conducted in 720 hospitals in 26 countries throughout North America, Latin America, Europe, and Asia-Pacific regions. The enrollment of 7226 patients hospitalized for ACS (myocardial infarction or unstable angina) with type 2 diabetes occurred between February 2010 and May 2012; treatment was planned to continue until patients were followed-up for at least 2.5 years and 950 primary end point events were positively adjudicated. Randomized in a 1:1 ratio to receive aleglitazar 150 µg or placebo daily. The primary efficacy end point was time to cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Principal safety end points were hospitalization due to heart failure and changes in renal function. The trial was terminated on July 2, 2013, after a median follow-up of 104 weeks, upon recommendation of the data and safety monitoring board due to futility for efficacy at an unplanned interim analysis and increased rates of safety end points. A total of 3.1% of patients were lost to follow-up and 3.2% of patients withdrew consent. The primary end point occurred in 344 patients (9.5%) in the aleglitazar group and 360 patients (10.0%) in the placebo group (hazard ratio, 0.96 [95% CI, 0.83-1.11]; P = .57). Rates of serious adverse events, including heart failure (3.4% for aleglitazar vs 2.8% for placebo, P = .14), gastrointestinal hemorrhages (2.4% for

  18. Hyperviscosity for unstructured ALE meshes

    NASA Astrophysics Data System (ADS)

    Cook, Andrew W.; Ulitsky, Mark S.; Miller, Douglas S.

    2013-01-01

    An artificial viscosity, originally designed for Eulerian schemes, is adapted for use in arbitrary Lagrangian-Eulerian simulations. Changes to the Eulerian model (dubbed 'hyperviscosity') are discussed, which enable it to work within a Lagrangian framework. New features include a velocity-weighted grid scale and a generalised filtering procedure, applicable to either structured or unstructured grids. The model employs an artificial shear viscosity for treating small-scale vorticity and an artificial bulk viscosity for shock capturing. The model is based on the Navier-Stokes form of the viscous stress tensor, including the diagonal rate-of-expansion tensor. A second-order version of the model is presented, in which Laplacian operators act on the velocity divergence and the grid-weighted strain-rate magnitude to ensure that the velocity field remains smooth at the grid scale. Unlike sound-speed-based artificial viscosities, the hyperviscosity model is compatible with the low Mach number limit. The new model outperforms a commonly used Lagrangian artificial viscosity on a variety of test problems.

  19. [Autism spectrum disorder and evaluation of perceived stress parents and professionals: Study of the psychometric properties of a French adaptation of the Appraisal of Life Event Scale (ALES-vf)].

    PubMed

    Cappe, É; Poirier, N; Boujut, É; Nader-Grosbois, N; Dionne, C; Boulard, A

    2017-08-01

    Autism and related disorders are grouped into the category of « Autism Spectrum Disorder » (ASD) in the DSM-5. This appellation reflects the idea of a dimensional representation of autism that combines symptoms and characteristics that vary in severity and intensity. Despite common characteristics, there are varying degrees in intensity and in the onset of symptoms, ranging from a disability that can be very heavy with a total lack of communication and major disorders associated with the existence of a relative autonomy associated, sometimes, with extraordinary intellectual abilities. Parents are faced with several difficult situations, such as sleep disturbances, agitation, shouting, hetero violence, self-harm, learning difficulties, stereotyping, lack of social and emotional reciprocity, inappropriate behavior, etc. They can feel helpless and may experience stress related to these developmental and behavioral difficulties. The heterogeneity of symptoms, the presence of behavioral problems, the lack of reciprocity and autonomy also represent a challenge for practitioners in institutions and teachers at school. The objective of this research is to present the validation of a French translation of the Appraisal of Life Events Scale (ALES-vf) from Ferguson, Matthex and Cox, specifically adapted to the context of ASD. ALES was originally developed to operationalize the three dimensions of perceived stress (threat, loss and challenge) described by Lazarus and Folkman. ALES-vf was initially translated into French and adapted to the situation of parents of children with ASD. It was subsequently administered to 343 parents, 150 paramedical professionals involved with people with ASD, and 155 teachers from an ordinary school environment and from specialized schools, welcoming in their classroom at least one child with ASD. An exploratory factor analysis performed on data from 170 parents highlighted two exploratory models with four and three factors, slightly different

  20. Efficacy of Clarithromycin-Naproxen-Oseltamivir Combination in the Treatment of Patients Hospitalized for Influenza A(H3N2) Infection: An Open-label Randomized, Controlled, Phase IIb/III Trial.

    PubMed

    Hung, Ivan F N; To, Kelvin K W; Chan, Jasper F W; Cheng, Vincent C C; Liu, Kevin S H; Tam, Anthony; Chan, Tuen-Ching; Zhang, Anna Jinxia; Li, Patrick; Wong, Tin-Lun; Zhang, Ricky; Cheung, Michael K S; Leung, William; Lau, Johnson Y N; Fok, Manson; Chen, Honglin; Chan, Kwok-Hung; Yuen, Kwok-Yung

    2017-05-01

    Influenza causes excessive hospitalizations and deaths. The study assessed the efficacy and safety of a clarithromycin-naproxen-oseltamivir combination for treatment of serious influenza. From February to April 2015, we conducted a prospective open-label, randomized, controlled trial. Adult patients hospitalized for A(H3N2) influenza were randomly assigned to a 2-day combination of clarithromycin 500 mg, naproxen 200 mg, and oseltamivir 75 mg twice daily, followed by 3 days of oseltamivir or to oseltamivir 75 mg twice daily without placebo for 5 days as a control method (1:1). The primary end point was 30-day mortality. The secondary end points were 90-day mortality, serial nasopharyngeal aspirate (NPA) virus titer, percentage of neuraminidase-inhibitor-resistant A(H3N2) virus (NIRV) quasispecies, pneumonia severity index (PSI), and duration of hospital stay. Among the 217 patients with influenza A(H3N2) enrolled, 107 were randomly assigned to the combination treatment. The median age was 80 years, and 53.5% were men. Adverse events were uncommon. Ten patients died during the 30-day follow-up. The combination treatment was associated with lower 30-day mortality (P = .01), less frequent high dependency unit admission (P = .009), and shorter hospital stay (P < .0001). The virus titer and PSI (days 1-3; P < .01) and the NPA specimens with NIRV quasispecies ≥ 5% (days 1-2; P < .01) were significantly lower in the combination treatment group. Multivariate analysis showed that combination treatment was the only independent factor associated with lower 30-day mortality (OR, 0.06; 95% CI, 0.004-0.94; P = .04). Combination treatment reduced both 30- and 90-day mortality and length of hospital stay. Further study of the antiviral and immunomodulatory effects of this combination treatment of severe influenza is warranted. BioMed Central; No.: ISRCTN11273879 DOI 10.1186/ISRCTN11273879; URL: www.isrctn.com/ISRCTN11273879. Copyright © 2016 American College

  1. On-line packed magnetic in-tube solid phase microextraction of acidic drugs such as naproxen and indomethacin by using Fe3O4@SiO2@layered double hydroxide nanoparticles with high anion exchange capacity.

    PubMed

    Shamsayei, Maryam; Yamini, Yadollah; Asiabi, Hamid; Safari, Meysam

    2018-02-22

    The authors describe a 3-component nanoparticle system composed of a silica-coated magnetite (Fe 3 O 4 ) core and a layered double (Cu-Cr) hydroxide nanoplatelet shell. The sorbent has a high anion exchange capacity for extraction anionic species. A simple online system, referred to as "on-line packed magnetic-in-tube solid phase microextraction" was designed. The nanoparticles were placed in a stainless steel cartridge via dry packing. The cartridge was then applied to the preconcentration acidic drugs including naproxen and indomethacin from urine and plasma. Extraction and desorption times, pH values of the sample solution and flow rates of sample solution and eluent were optimized. Analytes were then quantified by HPLC with UV detection. Under optimal conditions, the limits of detection range from 70 to 800 ng L -1 , with linear responses from 0.1-500 μg L -1 (water samples), 0.6-500 μg L -1 (spiked urine), and 0.9-500 μg L -1 (spiked plasma). The inter- and intra-assay precisions (RSDs, for n = 5) are in the range of 2.2-5.4%, 2.8-4.9%, and 2.0-5.2% at concentration levels of 5, 25 and 50 μg L -1 , respectively. The method was applied to the analysis of the drugs in spiked human urine and plasma, and good results were achieved. Graphical abstract Fe 3 O 4 @SiO 2 @CuCr-LDH magnetic nanoparticles were synthesized and packed in to a stainless steel column. The column was applied to solid phase microextraction of acidic drugs from biological samples.

  2. Application of carbon nanotubes modified with a Keggin polyoxometalate as a new sorbent for the hollow-fiber micro-solid-phase extraction of trace naproxen in hair samples with fluorescence spectrophotometry using factorial experimental design.

    PubMed

    Naddaf, Ezzat; Ebrahimi, Mahmoud; Es'haghi, Zarrin; Bamoharram, Fatemeh Farrash

    2015-07-01

    A sensitive technique to determinate naproxen in hair samples was developed using hollow-fiber micro-solid-phase combined with fluorescence spectrophotometry. The incorporation of multi-walled carbon nanotubes modified with a Keggin polyoxometalate into a silica matrix prepared by the sol-gel method was reported. In this research, the Keggin carbon nanotubes /silica composite was used in the pores and lumen of a hollow fiber as the hollow-fiber micro-solid-phase extraction device. The device was used for the microextraction of the analyte from hair and water samples under the optimized conditions. An orthogonal array experimental design with an OA24 (4(6) ) matrix was employed to optimize the conditions. The effect of six factors influencing the extraction efficiency was investigated: pH, salt, volume of donor and desorption phase, extraction and desorption time. The effect of each factor was estimated using individual contributions as response functions in the screening process. Analysis of variance was employed for estimating the main significant factors and their contributions in the extraction. Calibration curve plot displayed linearity over a range of 0.2-10 ng/mL with detection limits of 0.072 and 0.08 ng/mL for hair and aqueous samples, respectively. The relative recoveries in the hair and aqueous matrices ranged from 103-95%. The relative standard deviation for fiber-to-fiber repeatability was 3.9%. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. ALE: automated label extraction from GEO metadata.

    PubMed

    Giles, Cory B; Brown, Chase A; Ripperger, Michael; Dennis, Zane; Roopnarinesingh, Xiavan; Porter, Hunter; Perz, Aleksandra; Wren, Jonathan D

    2017-12-28

    NCBI's Gene Expression Omnibus (GEO) is a rich community resource containing millions of gene expression experiments from human, mouse, rat, and other model organisms. However, information about each experiment (metadata) is in the format of an open-ended, non-standardized textual description provided by the depositor. Thus, classification of experiments for meta-analysis by factors such as gender, age of the sample donor, and tissue of origin is not feasible without assigning labels to the experiments. Automated approaches are preferable for this, primarily because of the size and volume of the data to be processed, but also because it ensures standardization and consistency. While some of these labels can be extracted directly from the textual metadata, many of the data available do not contain explicit text informing the researcher about the age and gender of the subjects with the study. To bridge this gap, machine-learning methods can be trained to use the gene expression patterns associated with the text-derived labels to refine label-prediction confidence. Our analysis shows only 26% of metadata text contains information about gender and 21% about age. In order to ameliorate the lack of available labels for these data sets, we first extract labels from the textual metadata for each GEO RNA dataset and evaluate the performance against a gold standard of manually curated labels. We then use machine-learning methods to predict labels, based upon gene expression of the samples and compare this to the text-based method. Here we present an automated method to extract labels for age, gender, and tissue from textual metadata and GEO data using both a heuristic approach as well as machine learning. We show the two methods together improve accuracy of label assignment to GEO samples.

  4. Improved ALE mesh velocities for complex flows

    DOE PAGES

    Bakosi, Jozsef; Waltz, Jacob I.; Morgan, Nathaniel Ray

    2017-05-31

    A key choice in the development of arbitrary Lagrangian-Eulerian solution algorithms is how to move the computational mesh. The most common approaches are smoothing and relaxation techniques, or to compute a mesh velocity field that produces smooth mesh displacements. We present a method in which the mesh velocity is specified by the irrotational component of the fluid velocity as computed from a Helmholtz decomposition, and excess compression of mesh cells is treated through a noniterative, local spring-force model. This approach allows distinct and separate control over rotational and translational modes. In conclusion, the utility of the new mesh motion algorithmmore » is demonstrated on a number of 3D test problems, including problems that involve both shocks and significant amounts of vorticity.« less

  5. Migraine-related healthcare resource use and costs for subjects prescribed fixed-dose combination sumatriptan/naproxen sodium vs. single-entity oral triptans in a managed care population in the USA.

    PubMed

    Runken, M Chris; Goodwin, Bridgett; Shah, Manan; Eaddy, Michael; D'Souza, Anna; Bowers, Brian; Bell, Christopher F

    2015-02-01

    Randomized clinical trials have demonstrated that the efficacy of a fixed-dose single-tablet combination containing sumatriptan and naproxen sodium (S/NS) was greater than either of its individual components. Simplifying drug regimens (e.g., via a fixed-dose combination) has been shown to improve "real-world" outcomes by reducing pill burden and treatment regimen complexity, improving adherence, and reducing healthcare resource use and associated costs; however, no studies assessing such outcomes have been conducted to date for the acute treatment of migraine. To assess migraine-related healthcare resource use and associated costs for subjects prescribed S/NS vs. subjects prescribed single-entity oral triptans (SOTs) within a managed care population in the USA. In this retrospective analysis of administrative claims data from July 1, 2008 to December 31, 2009 (IMS LifeLink), subjects meeting the following criteria were selected: one or more pharmacy claim(s) for either S/NS or SOT (index date), aged 18-64 years; at least one migraine diagnosis, and continuous enrollment in the 6 months prior to and post the index date. The study population was subsequently stratified for two analyses: triptan-naïve (triptan naïve in the 6-month period prior to the index date) and triptan-switch (triptan user in the 6-month period prior to the index date and switching to another triptan). Subjects prescribed S/NS were propensity-score matched with subjects prescribed SOT (triptan-naïve analysis: 1:3; triptan-switch analysis: 1:1) to assess differences in healthcare resource use and associated costs (2009 US$) between the S/NS and SOT groups. Results from the triptan-naïve and triptan-switch analyses suggest that subjects prescribed S/NS are likely to have similar healthcare resource use patterns as those either newly initiated on an SOT or switching SOTs, as measured by migraine medication use, migraine-related healthcare resource use, and all-cause healthcare resource use. One

  6. 21 CFR 522.1468 - Naproxen for injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL.... Five milligrams per kilogram of body weight intravenously followed by maintenance oral therapy of 10 milligrams per kilogram of body weight twice daily for up to 14 consecutive days. (2) Indications for use...

  7. 21 CFR 522.1468 - Naproxen for injection.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL.... Five milligrams per kilogram of body weight intravenously followed by maintenance oral therapy of 10 milligrams per kilogram of body weight twice daily for up to 14 consecutive days. (2) Indications for use...

  8. 21 CFR 522.1468 - Naproxen for injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL.... Five milligrams per kilogram of body weight intravenously followed by maintenance oral therapy of 10 milligrams per kilogram of body weight twice daily for up to 14 consecutive days. (2) Indications for use...

  9. 21 CFR 522.1468 - Naproxen for injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL.... Five milligrams per kilogram of body weight intravenously followed by maintenance oral therapy of 10 milligrams per kilogram of body weight twice daily for up to 14 consecutive days. (2) Indications for use...

  10. 21 CFR 522.1468 - Naproxen for injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1468.... Five milligrams per kilogram of body weight intravenously followed by maintenance oral therapy of 10...

  11. AGT relations for abelian quiver gauge theories on ALE spaces

    NASA Astrophysics Data System (ADS)

    Pedrini, Mattia; Sala, Francesco; Szabo, Richard J.

    2016-05-01

    We construct level one dominant representations of the affine Kac-Moody algebra gl̂k on the equivariant cohomology groups of moduli spaces of rank one framed sheaves on the orbifold compactification of the minimal resolution Xk of the Ak-1 toric singularity C2 /Zk. We show that the direct sum of the fundamental classes of these moduli spaces is a Whittaker vector for gl̂k, which proves the AGT correspondence for pure N = 2 U(1) gauge theory on Xk. We consider Carlsson-Okounkov type Ext-bundles over products of the moduli spaces and use their Euler classes to define vertex operators. Under the decomposition gl̂k ≃ h ⊕sl̂k, these vertex operators decompose as products of bosonic exponentials associated to the Heisenberg algebra h and primary fields of sl̂k. We use these operators to prove the AGT correspondence for N = 2 superconformal abelian quiver gauge theories on Xk.

  12. Recovery Act Weekly Video: Upper ALE Building Demolition

    ScienceCinema

    None

    2017-12-11

    CH2MHILL Plateau Remediation Company demolition of 6652C Space Science Laboratory. The largest building atop Rattlesnake Mountain, the laboratory served as a nightly radar patrol center as well as a barracks. The Recovery Act funded project is helping reduce the site footprint.

  13. Litho-tectonic mapping of the North Afar region from Sentinel-2A multispectral imagery and ALOS AW3D30 digital elevation data: Controls on Danakil-Nubia plate motion between the Erta'Ale ridge and the Gulf of Zula

    NASA Astrophysics Data System (ADS)

    Hartnady, Chris; Hartnady, Michael; Wise, Edward; Blake, Dylan; McGibbon, David; Hay, E. Rowena

    2017-04-01

    The Danakil Depression in the North Afar region of Ethiopia reaches elevations deeper than 120 m below sea level and contains a Pleistocene-Holocene evaporite sequence currently investigated for potash mineral deposits. Separated from the main Ethiopian escarpment by the Dogua horst mountains, the asymmetric half-graben is bordered on its western (Nubian) side by the active, normal Main Danakil Rift-border Fault (MDRF). Above the MDRF, a series of piedmont alluvial fans (bajadas) fringes the Dogua Horst, emanating from a series of wadi catchments between the larger perennial rivers (Ragali, Saba) that drain from the high (>2000 m) Ethiopian Plateau. On its eastern side, the Danakil block contains Proterozoic-Palaeozoic sequences correlated with similar units in the Dogua range, and forms a microplate rotating independently between the larger Nubian and Arabian plates (McClusky et al., 2010). An understanding of the sedimentary and tectonic evolution of the Danakil-Nubia (DA-NU) plate system is crucial to the beneficial development of fresh groundwater resources and to an assessment of seismotectonic and volcanic geohazards in the area. Between the Mt Alid caldera in the Dandeiro graben and the Erta'Ale crater in the south Danakil, the rate of present-day DA-NU motion is 10.9 - 13.5 mm/yr, with direction azimuths N106E- N096E (after Schettino et al., 2016). DA-NU relative motion is focussed along the east-dipping MDRF in the Danakil but switches to an eastern (west-dipping) rift-border normal fault in the Dandiero, a northward extension of the Renda-Maglalla-Coma graben, separating the Dogua Horst from the main part of the NU plate. This change in rifting asymmetry occurs across a WNW/ESE-striking zone of basement faulting that terminates the Dogua Horst and functions as a left-stepping proto-transform fault zone, across the NNW direction of DA-NU proto-rift propagation. From 13-channel multispectral data of the European Space Agency satellite Sentinel-2A, a false

  14. Genotoxic response and oxidative stress induced by diclofenac, ibuprofen and naproxen in Daphnia magna.

    PubMed

    Gómez-Oliván, Leobardo Manuel; Galar-Martínez, Marcela; García-Medina, Sandra; Valdés-Alanís, Analleli; Islas-Flores, Hariz; Neri-Cruz, Nadia

    2014-10-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used pharmaceuticals in Mexico, but there is not proper regulation on the sale, use and disposal. These drugs can enter water bodies by diverse pathways, attaining significant concentrations and inducing damage on hydrobionts. To evaluate the oxidative stress and consequent damage to genetic material induced by DCF, IBP and NPX on Daphnia magna. The acute toxicity assays were performed to 48-h by nonsteroidal anti-inflammatory drugs evaluated. A sublethal assay were done after 48 h of exposure to DCF, IBP and NPX added to water with the concentration equivalent to the lowest observed adverse effect level (LOAEL), 9.7 mg/L for DCF, 2.9 mg/L for IBP and 0.017 mg/L for NPX. The DNA damage (comet assay) was evaluated at 12, 48 and 96 h. The oxidative biomarkers were evaluated: lipid peroxidation; protein carbonyl content; activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. D. magna exposed to DCF, IBP and NPX showed a significant increase (p < 0.05) with respect to controls in LPX. PCC was increased in IBP exposure. SOD and CAT activity were increased by exposure to IBP and NPX. GPX shows a significant increase with respect to control in IBP and DCF exposure and significant decrease by NPX exposure. DNA damage was observed in 48 and 96 h. DCF, IBP and NPX were responsible of alterations in biochemical biomarkers evaluated and DNA damage.

  15. Sustained Release of Naproxen in a New Kind Delivery System of Carbon Nanotubes Hydrogel

    PubMed Central

    Peng, Xiahui; Zhuang, Qiang; Peng, Dongming; Dong, Qiuli; Tan, Lini; Jiao, Feipeng; Liu, Linqi; Liu, jingyu; Zhao, Chenxi; Wang, Xiaomei

    2013-01-01

    In this paper, carbon nanotubes (CNTs) were added into chitosan (CS) hydrogels in the form of chitosan modified CNTs (CS-CNTs) composites to prepare carbon nanotubes hydrogels (CNTs-GEL). The products, named CS-MWCNTs, were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR) spectroscopy. Swelling properties and effect of pH on controlled release performance of the two kinds of hydrogels, CNTs- GEL and pure chitosan hydrogels without CNTs (GEL), were investigated respectively. The results showed that CNTs-GEL possess better controlled release performance than GEL. The releasing equilibrium time of CNTs-GEL was longer than that of GEL in both pH = w7.4 and pH=1.2 conditions, although the release ratios of the model drug are similar in the same pH buffer solutions. It is found that release kinetics is better fitted Ritger-Peppas empirical model indicating a fick-diffusion process in pH = 1.2, while in pH = 7.4 it was non-fick diffusion involving surface diffusion and corrosion diffusion processes. PMID:24523738

  16. Perception of affective and linguistic prosody: an ALE meta-analysis of neuroimaging studies.

    PubMed

    Belyk, Michel; Brown, Steven

    2014-09-01

    Prosody refers to the melodic and rhythmic aspects of speech. Two forms of prosody are typically distinguished: 'affective prosody' refers to the expression of emotion in speech, whereas 'linguistic prosody' relates to the intonation of sentences, including the specification of focus within sentences and stress within polysyllabic words. While these two processes are united by their use of vocal pitch modulation, they are functionally distinct. In order to examine the localization and lateralization of speech prosody in the brain, we performed two voxel-based meta-analyses of neuroimaging studies of the perception of affective and linguistic prosody. There was substantial sharing of brain activations between analyses, particularly in right-hemisphere auditory areas. However, a major point of divergence was observed in the inferior frontal gyrus: affective prosody was more likely to activate Brodmann area 47, while linguistic prosody was more likely to activate the ventral part of area 44. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  17. Perception of affective and linguistic prosody: an ALE meta-analysis of neuroimaging studies

    PubMed Central

    Brown, Steven

    2014-01-01

    Prosody refers to the melodic and rhythmic aspects of speech. Two forms of prosody are typically distinguished: ‘affective prosody’ refers to the expression of emotion in speech, whereas ‘linguistic prosody’ relates to the intonation of sentences, including the specification of focus within sentences and stress within polysyllabic words. While these two processes are united by their use of vocal pitch modulation, they are functionally distinct. In order to examine the localization and lateralization of speech prosody in the brain, we performed two voxel-based meta-analyses of neuroimaging studies of the perception of affective and linguistic prosody. There was substantial sharing of brain activations between analyses, particularly in right-hemisphere auditory areas. However, a major point of divergence was observed in the inferior frontal gyrus: affective prosody was more likely to activate Brodmann area 47, while linguistic prosody was more likely to activate the ventral part of area 44. PMID:23934416

  18. ALE OF TWO CLUSTERS YIELDS SECRETS OF STAR BIRTH IN THE EARLY UNIVERSE

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This NASA Hubble Space Telescope (HST) image shows rich detail, previously only seen in neighboring star birth regions, in a pair of star clusters 166,000 light-years away in the Large Magellanic Cloud (LMC), in the southern constellation Doradus. The field of view is 130 light-years across and was taken with the Wide Field Planetary Camera 2. HST's unique capabilities -- ultraviolet sensitivity, ability to see faint stars, and high resolution -- have been utilized fully to identify three separate populations in this concentration of nearly 10,000 stars down to the 25th magnitude (more that twice as many as can be seen over the entire sky with the naked eye on a clear night on Earth). The field of view is only 130 light-years across. Previous observations with ground-based telescopes resolve less than 1,000 stars in the same region. About 60 percent of the stars belong to the dominant yellow cluster called NGC 1850, which is estimated to be 50 million years old. A scattering of white stars in the image are massive stars that are only about 4 million years old and represent about 20 percent of the stars in the image. (The remainder are field stars in the LMC.) Besides being much younger, the white stars are much more loosely distributed than the yellow cluster. The significant difference between the two cluster ages suggests these are two separate star groups that lie along the same line of sight. The younger, more open cluster probably lies 200 light-years beyond the older cluster. If it were in the foreground, then dust contained in the white cluster would obscure stars in the older yellow cluster. To observe two well-defined star populations separated by such a small gap of space is unusual. This juxtaposition suggests that supernova explosions in the older cluster might have triggered the birth of the younger cluster. This color composite image is assembled from exposures taken in ultraviolet, visible, and near-infrared light. Yellow stars correspond to Main Sequence stars (like our Sun) with average surface temperatures of 6000 Kelvin; red stars are cool giants and supergiants (3500 K); white stars are hot young stars (25,000 K or more) that are bright in ultraviolet. Credit: R. Gilmozzi, Space Telescope Science Institute/European Space Agency; Shawn Ewald, JPL; and NASA

  19. An ALE meta-analysis on the audiovisual integration of speech signals.

    PubMed

    Erickson, Laura C; Heeg, Elizabeth; Rauschecker, Josef P; Turkeltaub, Peter E

    2014-11-01

    The brain improves speech processing through the integration of audiovisual (AV) signals. Situations involving AV speech integration may be crudely dichotomized into those where auditory and visual inputs contain (1) equivalent, complementary signals (validating AV speech) or (2) inconsistent, different signals (conflicting AV speech). This simple framework may allow the systematic examination of broad commonalities and differences between AV neural processes engaged by various experimental paradigms frequently used to study AV speech integration. We conducted an activation likelihood estimation metaanalysis of 22 functional imaging studies comprising 33 experiments, 311 subjects, and 347 foci examining "conflicting" versus "validating" AV speech. Experimental paradigms included content congruency, timing synchrony, and perceptual measures, such as the McGurk effect or synchrony judgments, across AV speech stimulus types (sublexical to sentence). Colocalization of conflicting AV speech experiments revealed consistency across at least two contrast types (e.g., synchrony and congruency) in a network of dorsal stream regions in the frontal, parietal, and temporal lobes. There was consistency across all contrast types (synchrony, congruency, and percept) in the bilateral posterior superior/middle temporal cortex. Although fewer studies were available, validating AV speech experiments were localized to other regions, such as ventral stream visual areas in the occipital and inferior temporal cortex. These results suggest that while equivalent, complementary AV speech signals may evoke activity in regions related to the corroboration of sensory input, conflicting AV speech signals recruit widespread dorsal stream areas likely involved in the resolution of conflicting sensory signals. Copyright © 2014 Wiley Periodicals, Inc.

  20. Coupled thermal/chemical/mechanical modeling of energetic materials in ALE3D

    NASA Technical Reports Server (NTRS)

    Nichols, A. L.; Couch, R.; Maltby, J. D.; McCallen, R. C.; Otero, I.

    1996-01-01

    We must improve our ability to model the response of energetic materials to thermal stimuli and the processes involved in the energetic response. We have developed and used a time step option to efficiently and accurately compute the hours that the energetic material can take to react. Since on these longer film scales, materials can be expected to have significant motion, it is even more important to provide high-order advection for all components, including the chemical species. We show an example cook-off problem to illustrate these capabilities.

  1. A 3D finite element ALE method using an approximate Riemann solution

    DOE PAGES

    Chiravalle, V. P.; Morgan, N. R.

    2016-08-09

    Arbitrary Lagrangian–Eulerian finite volume methods that solve a multidimensional Riemann-like problem at the cell center in a staggered grid hydrodynamic (SGH) arrangement have been proposed. This research proposes a new 3D finite element arbitrary Lagrangian–Eulerian SGH method that incorporates a multidimensional Riemann-like problem. Here, two different Riemann jump relations are investigated. A new limiting method that greatly improves the accuracy of the SGH method on isentropic flows is investigated. A remap method that improves upon a well-known mesh relaxation and remapping technique in order to ensure total energy conservation during the remap is also presented. Numerical details and test problemmore » results are presented.« less

  2. A 3D finite element ALE method using an approximate Riemann solution

    SciTech Connect

    Chiravalle, V. P.; Morgan, N. R.

    Arbitrary Lagrangian–Eulerian finite volume methods that solve a multidimensional Riemann-like problem at the cell center in a staggered grid hydrodynamic (SGH) arrangement have been proposed. This research proposes a new 3D finite element arbitrary Lagrangian–Eulerian SGH method that incorporates a multidimensional Riemann-like problem. Here, two different Riemann jump relations are investigated. A new limiting method that greatly improves the accuracy of the SGH method on isentropic flows is investigated. A remap method that improves upon a well-known mesh relaxation and remapping technique in order to ensure total energy conservation during the remap is also presented. Numerical details and test problemmore » results are presented.« less

  3. Aroma-active ester profile of ale beer produced under different fermentation and nutritional conditions.

    PubMed

    Hiralal, Lettisha; Olaniran, Ademola O; Pillay, Balakrishna

    2014-01-01

    A broad range of aroma-active esters produced during fermentation are vital for the complex flavour of beer. This study assessed the influence of fermentation temperature, pH, and wort nutritional supplements on the production of yeast-derived ester compounds and the overall fermentation performance. The best fermentation performance was achieved when wort was supplemented with 0.75 g/l l-leucine resulting in highest reducing sugar and FAN (free amino nitrogen) utilization and ethanol production. At optimum fermentation pH of 5, 38.27% reducing sugars and 35.28% FAN was utilized resulting in 4.07% (v/v) ethanol. Wort supplemented with zinc sulphate (0.12 g/l) resulted in 5.01% ethanol (v/v) production and 54.32% reducing sugar utilization. Increase in fermentation temperature from 18°C to room temperature (± 22.5°C) resulted in 17.03% increased ethanol production and 14.42% and 62.82% increase in total acetate ester concentration and total ethyl ester concentration, respectively. Supplementation of worth with 0.12 g/l ZnSO4 resulted in 2.46-fold increase in both isoamyl acetate and ethyl decanoate concentration, while a 7.05-fold and 1.96-fold increase in the concentration of isoamyl acetate and ethyl decanoate, respectively was obtained upon 0.75 g/l l-leucine supplementation. Wort supplemented with l-leucine (0.75 g/l) yielded the highest beer foam head stability with a rating of 2.67, while highest yeast viability was achieved when wort was supplemented with 0.12 g/l zinc sulphate. Results from this study suggest that supplementing wort with essential nutrients required for yeast growth and optimizing the fermentation conditions could be an effective way of improving fermentation performance and controlling aroma-active esters in beer. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  4. 47 CFR 80.229 - Special requirements for automatic link establishment (ALE).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... such signalling under the following conditions: (a) The transmitter power shall not exceed 100 W ERP... frequency bands must not exceed 10 µW peak ERP: (1) Protected frequencies (kHz) 2091.0 4188.0 6312.0 12290.0...

  5. 47 CFR 87.149 - Special requirements for automatic link establishment (ALE).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... exceed 100 W ERP; (b) Transmissions must sweep linearly in frequency at a rate of at least 60 kHz per... frequencies and frequency bands must not exceed 10 µW peak ERP: (1) Protected frequencies (kHz) 2091.0 4188.0...

  6. 47 CFR 80.229 - Special requirements for automatic link establishment (ALE).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... such signalling under the following conditions: (a) The transmitter power shall not exceed 100 W ERP... frequency bands must not exceed 10 µW peak ERP: (1) Protected frequencies (kHz) 2091.0 4188.0 6312.0 12290.0...

  7. Symmetry- and essentially-bound-preserving flux-corrected remapping of momentum in staggered ALE hydrodynamics

    NASA Astrophysics Data System (ADS)

    Velechovský, J.; Kuchařík, M.; Liska, R.; Shashkov, M.; Váchal, P.

    2013-12-01

    We present a new flux-corrected approach for remapping of velocity in the framework of staggered arbitrary Lagrangian-Eulerian methods. The main focus of the paper is the definition and preservation of coordinate invariant local bounds for velocity vector and development of momentum remapping method such that the radial symmetry of the radially symmetric flows is preserved when remapping from one equiangular polar mesh to another. The properties of this new method are demonstrated on a set of selected numerical cyclic remapping tests and a full hydrodynamic example.

  8. Neural network of cognitive emotion regulation — An ALE meta-analysis and MACM analysis

    PubMed Central

    Kohn, N.; Eickhoff, S.B.; Scheller, M.; Laird, A.R.; Fox, P.T.; Habel, U.

    2016-01-01

    Cognitive regulation of emotions is a fundamental prerequisite for intact social functioning which impacts on both well being and psychopathology. The neural underpinnings of this process have been studied intensively in recent years, without, however, a general consensus. We here quantitatively summarize the published literature on cognitive emotion regulation using activation likelihood estimation in fMRI and PET (23 studies/479 subjects). In addition, we assessed the particular functional contribution of identified regions and their interactions using quantitative functional inference and meta-analytic connectivity modeling, respectively. In doing so, we developed a model for the core brain network involved in emotion regulation of emotional reactivity. According to this, the superior temporal gyrus, angular gyrus and (pre) supplementary motor area should be involved in execution of regulation initiated by frontal areas. The dorsolateral prefrontal cortex may be related to regulation of cognitive processes such as attention, while the ventrolateral prefrontal cortex may not necessarily reflect the regulatory process per se, but signals salience and therefore the need to regulate. We also identified a cluster in the anterior middle cingulate cortex as a region, which is anatomically and functionally in an ideal position to influence behavior and subcortical structures related to affect generation. Hence this area may play a central, integrative role in emotion regulation. By focusing on regions commonly active across multiple studies, this proposed model should provide important a priori information for the assessment of dysregulated emotion regulation in psychiatric disorders. PMID:24220041

  9. Pathological And Immunological Study On Infection With Escherichia Coli In ale BALB/c mice

    NASA Astrophysics Data System (ADS)

    Ali, Intisar H.; Jabir, Majid S.; Al-Shmgani, Hanady S. A.; Sulaiman, Ghassan M.; Sadoon, Ali H.

    2018-05-01

    Escherichia coli bacteria is considered as one of the common responsible for the frequency and severity of infections that it hospitalized patients. E. coli simultaneously carries a harmful side in which only a slight genetic recombination can bring about a highly pathogenic strain that most frequently causes the scourge of bacterial infections worldwide including sepsis, neonatal meningitis, pneumonia, bacteremia and traveler’s diarrhea. This study was carried out to assess Escherichia coli infection induced pathologically and immunologically. Following Escherichia coli isolation, identification and counting, the lethal dose (LD-50) was determined before infection. Twenty-two mice were used in this study for 21 days infection, the animals were sacrificed at 3, 6, 9, 12, 15, 18 and 21 days, and tissues of different tissue were collected, examined for bacterial infection. Bacteria and mice immunization and ELISA were used to detect immunoglobulin G level in serum as well. For histological study, different infected organs were used. The results indicated that the LH50 was 1×109 cell; and all organs were infected after 3 days followed by decreased in infection level shown in brain at day 12, lung, kidney and intestine at day 15 and in liver, spleen and heart at day 21. Moreover, ELISA results revealed that concentration 1:200 of serum in positive and negative state and optimum concentration of Ag 1:40 dilution and compact dilution is 1:1000. In addition, diversity of histopathological alteration occurs in tissue on time-depended manner. This study concluded that the ability of activated E.coli to stimulate the intestinal secretory immune system of germ might result from a retardation of immunological maturity.

  10. Stuttering as a trait or state - an ALE meta-analysis of neuroimaging studies.

    PubMed

    Belyk, Michel; Kraft, Shelly Jo; Brown, Steven

    2015-01-01

    Stuttering is a speech disorder characterised by repetitions, prolongations and blocks that disrupt the forward movement of speech. An earlier meta-analysis of brain imaging studies of stuttering (Brown et al., 2005) revealed a general trend towards rightward lateralization of brain activations and hyperactivity in the larynx motor cortex bilaterally. The present study sought not only to update that meta-analysis with recent work but to introduce an important distinction not present in the first study, namely the difference between 'trait' and 'state' stuttering. The analysis of trait stuttering compares people who stutter (PWS) with people who do not stutter when behaviour is controlled for, i.e., when speech is fluent in both groups. In contrast, the analysis of state stuttering examines PWS during episodes of stuttered speech compared with episodes of fluent speech. Seventeen studies were analysed using activation likelihood estimation. Trait stuttering was characterised by the well-known rightward shift in lateralization for language and speech areas. State stuttering revealed a more diverse pattern. Abnormal activation of larynx and lip motor cortex was common to the two analyses. State stuttering was associated with overactivation in the right hemisphere larynx and lip motor cortex. Trait stuttering was associated with overactivation of lip motor cortex in the right hemisphere but underactivation of larynx motor cortex in the left hemisphere. These results support a large literature highlighting laryngeal and lip involvement in the symptomatology of stuttering, and disambiguate two possible sources of activation in neuroimaging studies of persistent developmental stuttering. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. A comparative study of interface reconstruction methods for multi-material ALE simulations

    SciTech Connect

    Kucharik, Milan; Garimalla, Rao; Schofield, Samuel

    2009-01-01

    In this paper we compare the performance of different methods for reconstructing interfaces in multi-material compressible flow simulations. The methods compared are a material-order-dependent Volume-of-Fluid (VOF) method, a material-order-independent VOF method based on power diagram partitioning of cells and the Moment-of-Fluid method (MOF). We demonstrate that the MOF method provides the most accurate tracking of interfaces, followed by the VOF method with the right material ordering. The material-order-independent VOF method performs some-what worse than the above two while the solutions with VOF using the wrong material order are considerably worse.

  12. Magneto-Hydrodynamic Simulations of a Magnetic Flux Compression Generator Using ALE3D

    DTIC Science & Technology

    2017-07-01

    armature ............................... 12 Fig. 10 Radial displacement of a point close to the armature at the axial position of 122 mm...13 Fig. 11 Radial displacement of the armature at 25-µs postdetonation time...right-hand side of image). In Fig. 10, a plot of the radial displacement history of a point on the armature located at the axial position of 122 mm. The

  13. The Analysis of AGEs and ALEs by Mass Spectrometry: What does the Future Hold?

    SciTech Connect

    Metz, Thomas O.

    2009-09-15

    In 1912, Louis-Camille Maillard described a reaction between amino acids and reducing sugars that produced a discolored (brown) reaction mixture in the presence of heat [1]. This complex network of reactions between reducing sugars and free amine groups on amino acids or proteins came to be known as the Maillard reaction and was the domain of food chemists for the next 50 years. Work in the 1960s began a very exciting era in the field. A few years earlier, several groups [2-5] reported on the heterogeneity of normal human adult hemoglobin (HbA) as determined chromatographically, and Allen et al weremore » the first to use cation-exchange chromatography to separate a previously observed fast moving component (HbAI) into three fractions that they termed AIa, AIb, and AIc. An increase in the fast moving HbAI of four diabetic patients was subsequently reported by Huisman and Dozy in 1962 [6], and the link between diabetes and increased HbAI was later strengthened by Rahbar’s observation of increased HbAI – the majority of which is HbAIc – in 47 cases of diabetes [7]. Bookchin and Gallop determined that HbAIc consisted of a hexose bound to both β-chains [8], and Bunn and colleagues subsequently proposed that glucose binds to the N-terminal amine groups of the β-chain valine residues in the form of a Schiff base, which then rearranges to form an Amadori compound [9]. Thus, while Maillard chemistry was known to occur during the heating and processing of food, the identification of Amadori-modified hemoglobin proved that it also occurred in vivo (after all, as John Baynes likes to point out, humans are essentially low temperature ovens with long cooking cycles!).« less

  14. ALE meta-analysis on facial judgments of trustworthiness and attractiveness.

    PubMed

    Bzdok, D; Langner, R; Caspers, S; Kurth, F; Habel, U; Zilles, K; Laird, A; Eickhoff, Simon B

    2011-01-01

    Faces convey a multitude of information in social interaction, among which are trustworthiness and attractiveness. Humans process and evaluate these two dimensions very quickly due to their great adaptive importance. Trustworthiness evaluation is crucial for modulating behavior toward strangers; attractiveness evaluation is a crucial factor for mate selection, possibly providing cues for reproductive success. As both dimensions rapidly guide social behavior, this study tests the hypothesis that both judgments may be subserved by overlapping brain networks. To this end, we conducted an activation likelihood estimation meta-analysis on 16 functional magnetic resonance imaging studies pertaining to facial judgments of trustworthiness and attractiveness. Throughout combined, individual, and conjunction analyses on those two facial judgments, we observed consistent maxima in the amygdala which corroborates our initial hypothesis. This finding supports the contemporary paradigm shift extending the amygdala's role from dominantly processing negative emotional stimuli to processing socially relevant ones. We speculate that the amygdala filters sensory information with evolutionarily conserved relevance. Our data suggest that such a role includes not only "fight-or-flight" decisions but also social behaviors with longer term pay-off schedules, e.g., trustworthiness and attractiveness evaluation. © Springer-Verlag 2010

  15. Purity Analysis of the Pharmaceuticals Naproxen and Propranolol: A Guided-Inquiry Laboratory Experiment in the Analytical Chemistry Laboratory

    ERIC Educational Resources Information Center

    Fakayode, Sayo O.

    2015-01-01

    Counterfeiting and adulteration of prescription drugs, herbal products, and food supplements are a global challenge, causing serious economic loss to drug marketers and health implications for humans. Accordingly, accurate determination of the purity of pharmaceuticals is critical for the quality assurance of prescription drugs. Herein, the first…

  16. Introspective Minds: Using ALE Meta-Analyses to Study Commonalities in the Neural Correlates of Emotional Processing, Social & Unconstrained Cognition

    PubMed Central

    Schilbach, Leonhard; Bzdok, Danilo; Timmermans, Bert; Fox, Peter T.; Laird, Angela R.; Vogeley, Kai; Eickhoff, Simon B.

    2012-01-01

    Previous research suggests overlap between brain regions that show task-induced deactivations and those activated during the performance of social-cognitive tasks. Here, we present results of quantitative meta-analyses of neuroimaging studies, which confirm a statistical convergence in the neural correlates of social and resting state cognition. Based on the idea that both social and unconstrained cognition might be characterized by introspective processes, which are also thought to be highly relevant for emotional experiences, a third meta-analysis was performed investigating studies on emotional processing. By using conjunction analyses across all three sets of studies, we can demonstrate significant overlap of task-related signal change in dorso-medial prefrontal and medial parietal cortex, brain regions that have, indeed, recently been linked to introspective abilities. Our findings, therefore, provide evidence for the existence of a core neural network, which shows task-related signal change during socio-emotional tasks and during resting states. PMID:22319593

  17. Neurological soft signs are not "soft" in brain structure and functional networks: evidence from ALE meta-analysis.

    PubMed

    Zhao, Qing; Li, Zhi; Huang, Jia; Yan, Chao; Dazzan, Paola; Pantelis, Christos; Cheung, Eric F C; Lui, Simon S Y; Chan, Raymond C K

    2014-05-01

    Neurological soft signs (NSS) are associated with schizophrenia and related psychotic disorders. NSS have been conventionally considered as clinical neurological signs without localized brain regions. However, recent brain imaging studies suggest that NSS are partly localizable and may be associated with deficits in specific brain areas. We conducted an activation likelihood estimation meta-analysis to quantitatively review structural and functional imaging studies that evaluated the brain correlates of NSS in patients with schizophrenia and other psychotic disorders. Six structural magnetic resonance imaging (sMRI) and 15 functional magnetic resonance imaging (fMRI) studies were included. The results from meta-analysis of the sMRI studies indicated that NSS were associated with atrophy of the precentral gyrus, the cerebellum, the inferior frontal gyrus, and the thalamus. The results from meta-analysis of the fMRI studies demonstrated that the NSS-related task was significantly associated with altered brain activation in the inferior frontal gyrus, bilateral putamen, the cerebellum, and the superior temporal gyrus. Our findings from both sMRI and fMRI meta-analyses further support the conceptualization of NSS as a manifestation of the "cerebello-thalamo-prefrontal" brain network model of schizophrenia and related psychotic disorders.

  18. IONCAP Prediction-Based Automatic Link Establishment (ALE) Frequency Selection for a Ten-Node Australian High-Frequency Network

    DTIC Science & Technology

    1994-07-11

    r. H %D -% P. Ilt %D 𔃺 in @ 1 %D% qv .~ m ’ S 4’ qwv nI"mm0" qva 0% 0% m% 0% 0% 0% 0% 4% 0% m’𔃾~ M 4 M enN9 e N N r4 V4 M P4 4 V4 4 N m 0%Cha %a 0% 0...3422). Reviewed and Approved: I 1 July 1994 Head, Submarine Electromagnetic Systems Department d REPORT DOCUMENTATION PAGE OMB Ao. 0700185 I I ow idd...SA me. muec de WW eew I igaid go Sevbad id WNmL SOW id S tlnm US kud.. uiliSŚy 1 1 aps 0" Wes ftf 12K0u -VAs.a mqgdumS asii Ut buADs Wila We~ham P

  19. Dissociations of cognitive inhibition, response inhibition, and emotional interference: Voxelwise ALE meta-analyses of fMRI studies.

    PubMed

    Hung, Yuwen; Gaillard, Schuyler L; Yarmak, Pavel; Arsalidou, Marie

    2018-06-19

    Inhibitory control is the stopping of a mental process with or without intention, conceptualized as mental suppression of competing information because of limited cognitive capacity. Inhibitory control dysfunction is a core characteristic of many major psychiatric disorders. Inhibition is generally thought to involve the prefrontal cortex; however, a single inhibitory mechanism is insufficient for interpreting the heterogeneous nature of human cognition. It remains unclear whether different dimensions of inhibitory processes-specifically cognitive inhibition, response inhibition, and emotional interference-rely on dissociated neural systems. We conducted systematic meta-analyses of fMRI studies in the BrainMap database supplemented by PubMed using whole-brain activation likelihood estimation. A total of 66 study experiments including 1,447 participants and 987 foci revealed that while the left anterior insula was concordant in all inhibitory dimensions, cognitive inhibition reliably activated specific dorsal frontal inhibitory system, engaging dorsal anterior cingulate, dorsolateral prefrontal cortex, and parietal areas, whereas emotional interference reliably implicated a ventral inhibitory system, involving the ventral surface of the inferior frontal gyrus and the amygdala. Response inhibition showed concordant clusters in the fronto-striatal system, including the dorsal anterior cingulate region and extended supplementary motor areas, the dorsal and ventral lateral prefrontal cortex, basal ganglia, midbrain regions, and parietal regions. We provide an empirically derived dimensional model of inhibition characterizing neural systems underlying different aspects of inhibitory mechanisms. This study offers a fundamental framework to advance current understanding of inhibition and provides new insights for future clinical research into disorders with different types of inhibition-related dysfunctions. © 2018 Wiley Periodicals, Inc.

  20. Neural foundation of human moral reasoning: an ALE meta-analysis about the role of personal perspective.

    PubMed

    Boccia, M; Dacquino, C; Piccardi, L; Cordellieri, P; Guariglia, C; Ferlazzo, F; Ferracuti, S; Giannini, A M

    2017-02-01

    Moral sense is defined as a feeling of the rightness or wrongness of an action that knowingly causes harm to people other than the agent. The large amount of data collected over the past decade allows drawing some definite conclusions about the neurobiological foundations of moral reasoning as well as a systematic investigation of methodological variables during fMRI studies. Here, we verified the existence of converging and consistent evidence in the current literature by means of a meta-analysis of fMRI studies of moral reasoning, using activation likelihood estimation meta-analysis. We also tested for a possible neural segregation as function of the perspective used during moral reasoning i.e., first or third person perspectives. Results demonstrate the existence of a wide network of areas underpinning moral reasoning, including orbitofrontal cortex, insula, amygdala, anterior cingulate cortex as well as precuneus and posterior cingulate cortex. Within this network we found a neural segregation as a function of the personal perspective, with 1PP eliciting higher activation in the bilateral insula and superior temporal gyrus as well as in the anterior cingulate cortex, lingual and fusiform gyri, middle temporal gyrus and precentral gyrus in the left hemisphere, and 3PP eliciting higher activation in the bilateral amygdala, the posterior cingulate cortex, insula and supramarginal gyrus in the left hemisphere as well as the medial and ventromedial prefrontal cortex in the right hemisphere. These results shed some more light on the contribution of these areas to moral reasoning, strongly supporting a functional specialization as a function of the perspective used during moral reasoning.

  1. Neural Systems Underlying Emotional and Non-emotional Interference Processing: An ALE Meta-Analysis of Functional Neuroimaging Studies

    PubMed Central

    Xu, Min; Xu, Guiping; Yang, Yang

    2016-01-01

    Understanding how the nature of interference might influence the recruitments of the neural systems is considered as the key to understanding cognitive control. Although, interference processing in the emotional domain has recently attracted great interest, the question of whether there are separable neural patterns for emotional and non-emotional interference processing remains open. Here, we performed an activation likelihood estimation meta-analysis of 78 neuroimaging experiments, and examined common and distinct neural systems for emotional and non-emotional interference processing. We examined brain activation in three domains of interference processing: emotional verbal interference in the face-word conflict task, non-emotional verbal interference in the color-word Stroop task, and non-emotional spatial interference in the Simon, SRC and Flanker tasks. Our results show that the dorsal anterior cingulate cortex (ACC) was recruited for both emotional and non-emotional interference. In addition, the right anterior insula, presupplementary motor area (pre-SMA), and right inferior frontal gyrus (IFG) were activated by interference processing across both emotional and non-emotional domains. In light of these results, we propose that the anterior insular cortex may serve to integrate information from different dimensions and work together with the dorsal ACC to detect and monitor conflicts, whereas pre-SMA and right IFG may be recruited to inhibit inappropriate responses. In contrast, the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) showed different degrees of activation and distinct lateralization patterns for different processing domains, which suggests that these regions may implement cognitive control based on the specific task requirements. PMID:27895564

  2. 3D Fluid-Structure Interaction Simulation of Aortic Valves Using a Unified Continuum ALE FEM Model.

    PubMed

    Spühler, Jeannette H; Jansson, Johan; Jansson, Niclas; Hoffman, Johan

    2018-01-01

    Due to advances in medical imaging, computational fluid dynamics algorithms and high performance computing, computer simulation is developing into an important tool for understanding the relationship between cardiovascular diseases and intraventricular blood flow. The field of cardiac flow simulation is challenging and highly interdisciplinary. We apply a computational framework for automated solutions of partial differential equations using Finite Element Methods where any mathematical description directly can be translated to code. This allows us to develop a cardiac model where specific properties of the heart such as fluid-structure interaction of the aortic valve can be added in a modular way without extensive efforts. In previous work, we simulated the blood flow in the left ventricle of the heart. In this paper, we extend this model by placing prototypes of both a native and a mechanical aortic valve in the outflow region of the left ventricle. Numerical simulation of the blood flow in the vicinity of the valve offers the possibility to improve the treatment of aortic valve diseases as aortic stenosis (narrowing of the valve opening) or regurgitation (leaking) and to optimize the design of prosthetic heart valves in a controlled and specific way. The fluid-structure interaction and contact problem are formulated in a unified continuum model using the conservation laws for mass and momentum and a phase function. The discretization is based on an Arbitrary Lagrangian-Eulerian space-time finite element method with streamline diffusion stabilization, and it is implemented in the open source software Unicorn which shows near optimal scaling up to thousands of cores. Computational results are presented to demonstrate the capability of our framework.

  3. 3D Fluid-Structure Interaction Simulation of Aortic Valves Using a Unified Continuum ALE FEM Model

    PubMed Central

    Spühler, Jeannette H.; Jansson, Johan; Jansson, Niclas; Hoffman, Johan

    2018-01-01

    Due to advances in medical imaging, computational fluid dynamics algorithms and high performance computing, computer simulation is developing into an important tool for understanding the relationship between cardiovascular diseases and intraventricular blood flow. The field of cardiac flow simulation is challenging and highly interdisciplinary. We apply a computational framework for automated solutions of partial differential equations using Finite Element Methods where any mathematical description directly can be translated to code. This allows us to develop a cardiac model where specific properties of the heart such as fluid-structure interaction of the aortic valve can be added in a modular way without extensive efforts. In previous work, we simulated the blood flow in the left ventricle of the heart. In this paper, we extend this model by placing prototypes of both a native and a mechanical aortic valve in the outflow region of the left ventricle. Numerical simulation of the blood flow in the vicinity of the valve offers the possibility to improve the treatment of aortic valve diseases as aortic stenosis (narrowing of the valve opening) or regurgitation (leaking) and to optimize the design of prosthetic heart valves in a controlled and specific way. The fluid-structure interaction and contact problem are formulated in a unified continuum model using the conservation laws for mass and momentum and a phase function. The discretization is based on an Arbitrary Lagrangian-Eulerian space-time finite element method with streamline diffusion stabilization, and it is implemented in the open source software Unicorn which shows near optimal scaling up to thousands of cores. Computational results are presented to demonstrate the capability of our framework. PMID:29713288

  4. Three-dimensional local ALE-FEM method for fluid flow in domains containing moving boundaries/objects interfaces

    SciTech Connect

    Carrington, David Bradley; Monayem, A. K. M.; Mazumder, H.

    2015-03-05

    A three-dimensional finite element method for the numerical simulations of fluid flow in domains containing moving rigid objects or boundaries is developed. The method falls into the general category of Arbitrary Lagrangian Eulerian methods; it is based on a fixed mesh that is locally adapted in the immediate vicinity of the moving interfaces and reverts to its original shape once the moving interfaces go past the elements. The moving interfaces are defined by separate sets of marker points so that the global mesh is independent of interface movement and the possibility of mesh entanglement is eliminated. The results is amore » fully robust formulation capable of calculating on domains of complex geometry with moving boundaries or devises that can also have a complex geometry without danger of the mesh becoming unsuitable due to its continuous deformation thus eliminating the need for repeated re-meshing and interpolation. Moreover, the boundary conditions on the interfaces are imposed exactly. This work is intended to support the internal combustion engines simulator KIVA developed at Los Alamos National Laboratories. The model's capabilities are illustrated through application to incompressible flows in different geometrical settings that show the robustness and flexibility of the technique to perform simulations involving moving boundaries in a three-dimensional domain.« less

  5. Factors Affecting Medial Temporal Lobe Engagement for Past and Future Episodic Events: An ALE Meta-Analysis of Neuroimaging Studies

    ERIC Educational Resources Information Center

    Viard, Armelle; Desgranges, Beatrice; Eustache, Francis; Piolino, Pascale

    2012-01-01

    Remembering the past and envisioning the future are at the core of one's sense of identity. Neuroimaging studies investigating the neural substrates underlying past and future episodic events have been growing in number. However, the experimental paradigms used to select and elicit episodic events vary greatly, leading to disparate results,…

  6. Procesamiento de señales radioastronómicas; implementación para la antena de espacio profundo DSA 3 de la Agencia Espacial Europea.

    NASA Astrophysics Data System (ADS)

    Cancio, A.; Colazo, M.; García, B.

    2017-10-01

    In December 2012, the European Space Agency opened its third Deep Space Station in Malargüe, province of Mendoza, Argentina. Due to the nature of its operations, the antenna has requirements for the stability of reference signals and low phase noise equipment that makes it a candidate for use in radio astronomy applications. The present work evaluates the first experience of observation of astronomical sources.

  7. Global average concentration and trend for hydroxyl radicals deduced from ALE/GAGE trichloroethane (methyl chloroform) data for 1978-1990

    NASA Technical Reports Server (NTRS)

    Prinn, R.; Cunnold, D.; Simmonds, P.; Alyea, F.; Boldi, R.; Crawford, A.; Fraser, P.; Gutzler, D.; Hartley, D.; Rosen, R.

    1992-01-01

    An optimal estimation inversion scheme is utilized with atmospheric data and emission estimates to determined the globally averaged CH3CCl3 tropospheric lifetime and OH concentration. The data are taken from atmospheric measurements from surface stations of 1,1,1-trichloroethane and show an annual increase of 4.4 +/- 0.2 percent. Industrial emission estimates and a small oceanic loss rate are included, and the OH concentration for the same period (1978-1990) are incorporated at 1.0 +/- 0.8 percent/yr. The positive OH trend is consistent with theories regarding OH and ozone trends with respect to land use and global warming. Attention is given to the effects of the ENSO on the CH3CCl3 data and the assumption of continuing current industrial anthropogenic emissions. A novel tropical atmospheric tracer-transport mechanism is noted with respect to the CH3CCl3 data.

  8. Differentiating between self and others: an ALE meta-analysis of fMRI studies of self-recognition and theory of mind.

    PubMed

    van Veluw, Susanne J; Chance, Steven A

    2014-03-01

    The perception of self and others is a key aspect of social cognition. In order to investigate the neurobiological basis of this distinction we reviewed two classes of task that study self-awareness and awareness of others (theory of mind, ToM). A reliable task to measure self-awareness is the recognition of one's own face in contrast to the recognition of others' faces. False-belief tasks are widely used to identify neural correlates of ToM as a measure of awareness of others. We performed an activation likelihood estimation meta-analysis, using the fMRI literature on self-face recognition and false-belief tasks. The brain areas involved in performing false-belief tasks were the medial prefrontal cortex (MPFC), bilateral temporo-parietal junction, precuneus, and the bilateral middle temporal gyrus. Distinct self-face recognition regions were the right superior temporal gyrus, the right parahippocampal gyrus, the right inferior frontal gyrus/anterior cingulate cortex, and the left inferior parietal lobe. Overlapping brain areas were the superior temporal gyrus, and the more ventral parts of the MPFC. We confirmed that self-recognition in contrast to recognition of others' faces, and awareness of others involves a network that consists of separate, distinct neural pathways, but also includes overlapping regions of higher order prefrontal cortex where these processes may be combined. Insights derived from the neurobiology of disorders such as autism and schizophrenia are consistent with this notion.

  9. The role of the salience network in processing lexical and nonlexical stimuli in cochlear implant users: an ALE meta-analysis of PET studies.

    PubMed

    Song, Jae-Jin; Vanneste, Sven; Lazard, Diane S; Van de Heyning, Paul; Park, Joo Hyun; Oh, Seung Ha; De Ridder, Dirk

    2015-05-01

    Previous positron emission tomography (PET) studies have shown that various cortical areas are activated to process speech signal in cochlear implant (CI) users. Nonetheless, differences in task dimension among studies and low statistical power preclude from understanding sound processing mechanism in CI users. Hence, we performed activation likelihood estimation meta-analysis of PET studies in CI users and normal hearing (NH) controls to compare the two groups. Eight studies (58 CI subjects/92 peak coordinates; 45 NH subjects/40 peak coordinates) were included and analyzed, retrieving areas significantly activated by lexical and nonlexical stimuli. For lexical and nonlexical stimuli, both groups showed activations in the components of the dual-stream model such as bilateral superior temporal gyrus/sulcus, middle temporal gyrus, left posterior inferior frontal gyrus, and left insula. However, CI users displayed additional unique activation patterns by lexical and nonlexical stimuli. That is, for the lexical stimuli, significant activations were observed in areas comprising salience network (SN), also known as the intrinsic alertness network, such as the left dorsal anterior cingulate cortex (dACC), left insula, and right supplementary motor area in the CI user group. Also, for the nonlexical stimuli, CI users activated areas comprising SN such as the right insula and left dACC. Previous episodic observations on lexical stimuli processing using the dual auditory stream in CI users were reconfirmed in this study. However, this study also suggests that dual-stream auditory processing in CI users may need supports from the SN. In other words, CI users need to pay extra attention to cope with degraded auditory signal provided by the implant. © 2015 Wiley Periodicals, Inc.

  10. Draft Genome Sequence of the Novel Thermoacidophilic Archaeon Acidianus copahuensis Strain ALE1, Isolated from the Copahue Volcanic Area in Neuquén, Argentina

    PubMed Central

    Rascovan, Nicolás; Castro, Camila; Revale, Santiago; Giaveno, M. Alejandra; Vazquez, Martín; Donati, Edgardo R.

    2014-01-01

    Acidianus copahuensis is a recently characterized thermoacidophilic archaeon isolated from the Copahue volcanic area in Argentina. Here, we present its draft genome sequence, in which we found genes involved in key metabolic pathways for developing under Copahue’s extreme environmental conditions, such as sulfur and iron oxidation, carbon fixation, and metal tolerance. PMID:24812211

  11. Premenstrual Syndrome (PMS)

    MedlinePlus

    ... headaches, backaches, and breast tenderness. These include: Ibuprofen Naproxen Aspirin Some women find that taking an over- ... headaches, backaches, and breast tenderness. These include: Ibuprofen Naproxen Aspirin Some women find that taking an over- ...

  12. Vitamin D-Prostaglandin Interactions and Effects in Prostate Cancer

    DTIC Science & Technology

    2006-10-01

    combining high doses of calcitriol and naproxen in PCa patients with advanced androgen-independent disease who have failed other therapies. The initial...growth inhibitory actions of calcitriol. Potential Mediators of the Enhanced Growth Inhibition by the combined treatment with Calcitriol and Naproxen ...specific NSAIDs ( naproxen and ibuprofen). To explore the possible molecular mechanisms mediating this enhanced growth inhibition, we analyzed the

  13. Clinical Investigation Program Report.

    DTIC Science & Technology

    1983-10-01

    metastatic to liver. (0) H-83-63. Double-blind, randomized parallel comparison of two different dosage regimens of naproxen sodium in patients with...different dosage regimens of naproxen sodium in patients with bone pain due to m etastatic cancer. Start Date: May 83 Est Comp Date: Indefinite Principal...Investigator: Facility: LTC D Gandara, MD LAMC CPT R Mansour, MD D ept/Svc: Associate Investigators: Hematology-Oncology Key Words: naproxen sodium

  14. Journal of Special Operations Medicine, Volume 3, Edition 2

    DTIC Science & Technology

    2003-01-01

    NREMT program. However, the overall resounding rejection was that it differed from many organic military medical tasks and sup- planted those tasks...Mobic®) · Naproxen (Naprosyn®) · Naproxen sodium (Anaprox®, Alleve®) · Nabumetone (Relafen®) · Oxaprozin (Daypro®) · Piroxicam (Feldene®) · Sulindac...to sodium naproxen and ibuprofen.18 The manufac- turer recommends against the chronic use of 50mg dosing for acute pain.19 Further studies are needed

  15. Rethinking the role of the rTPJ in attention and social cognition in light of the opposing domains hypothesis: findings from an ALE-based meta-analysis and resting-state functional connectivity

    PubMed Central

    Kubit, Benjamin; Jack, Anthony I.

    2013-01-01

    The right temporo-parietal junction (rTPJ) has been associated with two apparently disparate functional roles: in attention and in social cognition. According to one account, the rTPJ initiates a “circuit-breaking” signal that interrupts ongoing attentional processes, effectively reorienting attention. It is argued this primary function of the rTPJ has been extended beyond attention, through a process of evolutionarily cooption, to play a role in social cognition. We propose an alternative account, according to which the capacity for social cognition depends on a network which is both distinct from and in tension with brain areas involved in focused attention and target detection: the default mode network (DMN). Theory characterizing the rTPJ based on the area's purported role in reorienting may be falsely guided by the co-occurrence of two distinct effects in contiguous regions: activation of the supramarginal gyrus (SMG), associated with its functional role in target detection; and the transient release, during spatial reorienting, of suppression of the angular gyrus (AG) associated with focused attention. Findings based on meta-analysis and resting functional connectivity are presented which support this alternative account. We find distinct regions, possessing anti-correlated patterns of resting connectivity, associated with social reasoning (AG) and target detection (SMG) at the rTPJ. The locus for reorienting was spatially intermediate between the AG and SMG and showed a pattern of connectivity with similarities to social reasoning and target detection seeds. These findings highlight a general methodological concern for brain imaging. Given evidence that certain tasks not only activate some areas but also suppress activity in other areas, it is suggested that researchers need to distinguish two distinct putative mechanisms, either of which may produce an increase in activity in a brain area: functional engagement in the task vs. release of suppression. PMID:23847497

  16. Managing Radiation Therapy Side Effects: What to Do When You Have Loose Stools (Diarrhea)

    MedlinePlus

    ... Drink lots of clear liquids, such as water, ginger ale, and clear soup. n Most people who ... beef Drinks (clear liquids) • Clear soda, such as ginger ale • Cranberry or grape juice • Oral rehydration solution ...

  17. Morning sickness

    MedlinePlus

    ... Bland foods, such as gelatin, frozen desserts, broth, ginger ale, and saltine crackers, also soothe the stomach. ... your stomach does not get too full. Seltzer, ginger ale, or other sparkling waters may help control ...

  18. Active Learning in Engineering Education: A (Re)Introduction

    ERIC Educational Resources Information Center

    Lima, Rui M.; Andersson, Pernille Hammar; Saalman, Elisabeth

    2017-01-01

    The informal network "Active Learning in Engineering Education" (ALE) has been promoting Active Learning since 2001. ALE creates opportunity for practitioners and researchers of engineering education to collaboratively learn how to foster learning of engineering students. The activities in ALE are centred on the vision that learners…

  19. A practical approach to reduce interference due to in-source collision-induced dissociation of acylglucuronides in LC-MS/MS.

    PubMed

    Mess, Jean-Nicholas; Bérubé, Eugénie-Raphaelle; Furtado, Milton; Garofolo, Fabio

    2011-08-01

    In LC-MS/MS, glucuronide conjugated metabolites may convert back to the parent drug due to in-source collision-induced dissociation (CID). During the bioanalysis of naproxen, it was noticed that naproxen acylglucuronide exhibited intense in-source CID to the naproxen [M+H](+) ion under positive ESI. However, no in-source CID of the acylglucuronide to the naproxen [M+NH(4)](+) adduct was observed. Furthermore, absolutely no in-source CID was detected under negative ESI. This phenomenon was not only observed for naproxen acylglucuronide but for eight other acylglucuronides compounds. We have shown that monitoring the parent drug [M-H](-) or [M+NH(4)](+) whenever possible could be an easy approach used by bioanalytical scientists to minimize the impact of in-source CID of acylglucuronides to the parent drug.

  20. Overview of atomic layer etching in the semiconductor industry

    SciTech Connect

    Kanarik, Keren J., E-mail: keren.kanarik@lamresearch.com; Lill, Thorsten; Hudson, Eric A.

    2015-03-15

    Atomic layer etching (ALE) is a technique for removing thin layers of material using sequential reaction steps that are self-limiting. ALE has been studied in the laboratory for more than 25 years. Today, it is being driven by the semiconductor industry as an alternative to continuous etching and is viewed as an essential counterpart to atomic layer deposition. As we enter the era of atomic-scale dimensions, there is need to unify the ALE field through increased effectiveness of collaboration between academia and industry, and to help enable the transition from lab to fab. With this in mind, this article providesmore » defining criteria for ALE, along with clarification of some of the terminology and assumptions of this field. To increase understanding of the process, the mechanistic understanding is described for the silicon ALE case study, including the advantages of plasma-assisted processing. A historical overview spanning more than 25 years is provided for silicon, as well as ALE studies on oxides, III–V compounds, and other materials. Together, these processes encompass a variety of implementations, all following the same ALE principles. While the focus is on directional etching, isotropic ALE is also included. As part of this review, the authors also address the role of power pulsing as a predecessor to ALE and examine the outlook of ALE in the manufacturing of advanced semiconductor devices.« less

  1. Hydrogen sulphide protects against NSAID-enteropathy through modulation of bile and the microbiota

    PubMed Central

    Blackler, Rory W; Motta, Jean-Paul; Manko, Anna; Workentine, Matthew; Bercik, Premysl; Surette, Michael G; Wallace, John L

    2015-01-01

    Background and Purpose Hydrogen sulphide is an important mediator of gastrointestinal mucosal defence. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is significantly limited by their toxicity in the gastrointestinal tract. Particularly concerning is the lack of effective preventative or curative treatments for NSAID-induced intestinal damage and bleeding. We evaluated the ability of a hydrogen sulphide donor to protect against NSAID-induced enteropathy. Experimental Approach Intestinal ulceration and bleeding were induced in Wistar rats by oral administration of naproxen. The effects of suppression of endogenous hydrogen sulphide synthesis or administration of a hydrogen sulphide donor (diallyl disulphide) on naproxen-induced enteropathy was examined. Effects of diallyl disulphide on small intestinal inflammation and intestinal microbiota were also assessed. Bile collected after in vivo naproxen and diallyl disulphide administration was evaluated for cytotoxicity in vitro using cultured intestinal epithelial cells. Key Results Suppression of endogenous hydrogen sulphide synthesis by β-cyano-L-alanine exacerbated naproxen-induced enteropathy. Diallyl disulphide co-administration dose-dependently reduced the severity of naproxen-induced small intestinal damage, inflammation and bleeding. Diallyl disulphide administration attenuated naproxen-induced increases in the cytotoxicity of bile on cultured enterocytes, and prevented or reversed naproxen-induced changes in the intestinal microbiota. Conclusions and Implications Hydrogen sulphide protects against NSAID-enteropathy in rats, in part reducing the cytotoxicity of bile and preventing NSAID-induced dysbiosis. PMID:25297699

  2. Modeling of Complex Coupled Fluid-Structure Interaction Systems in Arbitrary Water Depth

    DTIC Science & Technology

    2008-01-01

    model in a particle finite element method ( PFEM ) based framework for the ALE-RANS solver and submitted a journal paper recently [1]. In the paper, we...developing a fluid-flexible structure interaction model without free surface using ALE-RANS and k-ε turbulence closure model implemented by PFEM . In...the ALE_RANS and k-ε turbulence closure model based on the particle finite element Method ( PFEM ) and obtained some satisfying results [1-2]. The

  3. 15 CFR Supplement No. 1 to Part 746 - Examples of Luxury Goods

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... (other than public transport), including station wagons (3) Racing cars, snowmobiles, and motorcycles (4...) Musical instruments (2) Recreational sports equipment (i) Alcoholic beverages: wine, beer, ales, and...

  4. 15 CFR Supplement No. 1 to Part 746 - Examples of Luxury Goods

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... (other than public transport), including station wagons (3) Racing cars, snowmobiles, and motorcycles (4...) Musical instruments (2) Recreational sports equipment (i) Alcoholic beverages: wine, beer, ales, and...

  5. 15 CFR Supplement No. 1 to Part 746 - Examples of Luxury Goods

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... (other than public transport), including station wagons (3) Racing cars, snowmobiles, and motorcycles (4...) Musical instruments (2) Recreational sports equipment (i) Alcoholic beverages: wine, beer, ales, and...

  6. 15 CFR Supplement No. 1 to Part 746 - Examples of Luxury Goods

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... (other than public transport), including station wagons (3) Racing cars, snowmobiles, and motorcycles (4...) Musical instruments (2) Recreational sports equipment (i) Alcoholic beverages: wine, beer, ales, and...

  7. Insensitive Munitions Modeling Improvement Efforts

    DTIC Science & Technology

    2010-10-01

    LLNL) ALE3D . Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to...codes most commonly used by munition designers are CTH and the SIERRA suite of codes produced by Sandia National Labs (SNL) and ALE3D produced by... ALE3D , a LLNL developed code, is also used by various DoD participants. It was however, designed differently than either CTH or Sierra. ALE3D is a

  8. Azilsartan

    MedlinePlus

    ... It works by blocking the action of certain natural substances that tighten the blood vessels, allowing the ... Advil, Motrin) and naproxen (Aleve, Naprosyn) and selective COX-2 inhibitors such as celecoxib (Celebrex); diuretics ('water pills'); lithium ( ...

  9. Blepharoplasty (Eyelid Surgery)

    MedlinePlus

    ... also ask about your use of medications, vitamins, herbal supplements, alcohol, tobacco and drugs. Your expectations. An honest ... others), naproxen (Naprosyn), and any other medication or herbal supplement associated with increased bleeding. Ask your doctor how ...

  10. Endometriosis

    MedlinePlus

    ... ibuprofen (Advil), naproxen (Aleve), and acetaminophen (Tylenol). Prescription painkillers, if needed, for more severe pain. Regular exams ... or injections -- This treatment helps shrink growths. Side effects may include weight gain and depression. Gonadotropin-agonist ...

  11. Pain: Hope through Research

    MedlinePlus

    ... and naproxen) are widely prescribed and sometimes called non-narcotic or non-opioid analgesics. They work by reducing inflammatory responses ... life in older people. The guidelines contained several non-drug approaches to treatment, including exercise, and recommended ...

  12. Carotid artery surgery

    MedlinePlus

    ... of stroke. Some of these medicines are aspirin, clopidogrel (Plavix), and warfarin (Coumadin). Carotid angioplasty and stenting is ... thinner drugs. These include aspirin, ibuprofen (Advil, Motrin), ... (Plavix), naprosyn (Aleve, Naproxen), and other drugs like ...

  13. Plantar Fasciitis

    MedlinePlus

    ... medicine help? Aspirin, acetaminophen (one brand name: Tylenol), naproxen (brand name: Aleve), or ibuprofen (some brand names: ... Kids and Teens, Men, WomenTags: fasciitis, foot, heel, plant, soreness September 1, 2000 Copyright © American Academy of ...

  14. Yerba Mate

    MedlinePlus

    Mate is a plant. The leaves are used to make medicine. Mate is used as a stimulant to relieve mental and physical tiredness ( ... diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ...

  15. Grape

    MedlinePlus

    ... fruit, skin, leaves and seed of the grape plant are used as medicine. Grape seeds are by- ... haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), mirtazapine (Remeron), naproxen (Naprosyn), nortriptyline (Pamelor), olanzapine (Zyprexa), ondansetron (Zofran), propafenone ( ...

  16. Fucus Vesiculosus

    MedlinePlus

    ... type of brown seaweed. People use the whole plant to make medicine. People use Fucus vesiculosus for ... diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ...

  17. Migraines

    MedlinePlus

    ... name: Excedrin Migraine); ibuprofen (one brand name: Motrin); naproxen (brand name: Aleve); and ketoprofen (brand name: Orudis ... and leaf and root extracts of the butterbur plant. What else can I do to prevent migraines? ...

  18. Managing Osteoarthritis Pain with Medicines: A Review of the Research for Adults

    MedlinePlus

    ... much you buy at one time. When you shop around for the best price, you should also consider the quality of the product. 7 Wholesale Prices of Prescription Analgesics Drug Name NSAIDs Celecoxib Ibuprofen Diclofenac Naproxen Etodolac Meloxicam ...

  19. Pain Relievers: MedlinePlus Health Topic

    MedlinePlus

    ... are two main types of OTC pain medicines: acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin, naproxen ( ... American Rhinologic Society) Don't Double Up on Acetaminophen (Food and Drug Administration) Also in Spanish Narcotic ...

  20. Peptic ulcer

    MedlinePlus

    ... ulcers: Drinking too much alcohol Regular use of aspirin, ibuprofen, naproxen, or other nonsteroidal anti-inflammatory drugs ( ... pylori infection. Your ulcer is caused by taking aspirin or NSAIDs. Your doctor may also prescribe this ...

  1. Vitamin D-Prostaglandin Interactions and Effects on Prostate Cancer

    DTIC Science & Technology

    2005-10-01

    We propose that a combination of calcitriol and a nonselective NSAID, such as naproxen , might be a useful therapeutic and/or chemo-preventive strategy...their growth inhibitory planting clinical prostate tumors or cultured human PCa actions [25]. These results strongly suggest that the combi- cells into...flufenamnic acid, sulindac sulfide, c-fos mRNA was determined as an indicator of the biological indomethacin, naproxen , and ibuprofen. Figure 5A to D

  2. Cell Cycle Target-based Therapy for Ovarian Cancer

    DTIC Science & Technology

    2008-09-01

    induces apoptosis in quiescent ovarian cancer cells. Strong inducers of apoptosis included flufenamic acid, flurbiprofen, celebrex and finasteride ...Thus, a whole panel of NSAIDs including Aspirin, Ibuprofen, Exisulind, Acetaminophen, Naproxen, NS-398, Celecoxib, Diclofenac, Finasteride ...Naproxen, 200µM NS-398, 50µM Celecoxib, 200µM Diclofenac, 50µM Finasteride , 200µM Flufenamic acid, 40µM Meloxican, 50µM Ebselen, 20nM Flurbiprofen or

  3. Predicting synergy in atomic layer etching

    SciTech Connect

    Kanarik, Keren J.; Tan, Samantha; Yang, Wenbing

    2017-03-27

    Atomic layer etching (ALE) is a multistep process used today in manufacturing for removing ultrathin layers of material. In this article, the authors report on ALE of Si, Ge, C, W, GaN, and SiO 2 using a directional (anisotropic) plasma-enhanced approach. The authors analyze these systems by defining an “ALE synergy” parameter which quantifies the degree to which a process approaches the ideal ALE regime. This parameter is inspired by the ion-neutral synergy concept introduced in the 1979 paper by Coburn and Winters. ALE synergy is related to the energetics of underlying surface interactions and is understood in terms ofmore » energy criteria for the energy barriers involved in the reactions. Synergistic behavior is observed for all of the systems studied, with each exhibiting behavior unique to the reactant–material combination. By systematically studying atomic layer etching of a group of materials, the authors show that ALE synergy scales with the surface binding energy of the bulk material. This insight explains why some materials are more or less amenable to the directional ALE approach. Furthermore, they conclude that ALE is both simpler to understand than conventional plasma etch processing and is applicable to metals, semiconductors, and dielectrics.« less

  4. Blast Fragmentation Modeling and Analysis

    DTIC Science & Technology

    2010-10-31

    weapons device containing a multiphase blast explosive (MBX). 1. INTRODUCTION The ARL Survivability Lethality and Analysis Directorate (SLAD) is...velocity. In order to simulate the highly complex phenomenon, the exploding cylinder is modeled with the hydrodynamics code ALE3D , an arbitrary...Lagrangian-Eulerian multiphysics code, developed at Lawrence Livermore National Laboratory. ALE3D includes physical properties, constitutive models for

  5. Differences in effectiveness of the active living every day program for older adults with arthritis.

    PubMed

    Sperber, Nina R; Allen, Kelli D; Devellis, Brenda M; Devellis, Robert F; Lewis, Megan A; Callahan, Leigh F

    2013-10-01

    The authors explored whether demographic and psychosocial variables predicted differences in physical activity for participants with arthritis in a trial of Active Living Every Day (ALED). Participants (N = 280) from 17 community sites were randomized into ALED or usual care. The authors assessed participant demographic characteristics, self-efficacy, outcome expectations, pain, fatigue, and depressive symptoms at baseline and physical activity frequency at 20-wk follow-up. They conducted linear regression with interaction terms (Baseline Characteristic × Randomization Group). Being female (p ≤ .05), less depressed (p ≤ .05), or younger (p ≤ .10) was associated with more frequent posttest physical activity for ALED participants than for those with usual care. Higher education was associated with more physical activity for both ALED and usual-care groups. ALED was particularly effective for female, younger, and less depressed participants. Further research should determine whether modifications could produce better outcomes in other subgroups.

  6. Consequences of atomic layer etching on wafer scale uniformity in inductively coupled plasmas

    NASA Astrophysics Data System (ADS)

    Huard, Chad M.; Lanham, Steven J.; Kushner, Mark J.

    2018-04-01

    Atomic layer etching (ALE) typically divides the etching process into two self-limited reactions. One reaction passivates a single layer of material while the second preferentially removes the passivated layer. As such, under ideal conditions the wafer scale uniformity of ALE should be independent of the uniformity of the reactant fluxes onto the wafers, provided all surface reactions are saturated. The passivation and etch steps should individually asymptotically saturate after a characteristic fluence of reactants has been delivered to each site. In this paper, results from a computational investigation are discussed regarding the uniformity of ALE of Si in Cl2 containing inductively coupled plasmas when the reactant fluxes are both non-uniform and non-ideal. In the parameter space investigated for inductively coupled plasmas, the local etch rate for continuous processing was proportional to the ion flux. When operated with saturated conditions (that is, both ALE steps are allowed to self-terminate), the ALE process is less sensitive to non-uniformities in the incoming ion flux than continuous etching. Operating ALE in a sub-saturation regime resulted in less uniform etching. It was also found that ALE processing with saturated steps requires a larger total ion fluence than continuous etching to achieve the same etch depth. This condition may result in increased resist erosion and/or damage to stopping layers using ALE. While these results demonstrate that ALE provides increased etch depth uniformity, they do not show an improved critical dimension uniformity in all cases. These possible limitations to ALE processing, as well as increased processing time, will be part of the process optimization that includes the benefits of atomic resolution and improved uniformity.

  7. Aloe vera extract functionalized zinc oxide nanoparticles as nanoantibiotics against multi-drug resistant clinical bacterial isolates.

    PubMed

    Ali, Khursheed; Dwivedi, Sourabh; Azam, Ameer; Saquib, Quaiser; Al-Said, Mansour S; Alkhedhairy, Abdulaziz A; Musarrat, Javed

    2016-06-15

    ZnO nanoparticles (ZnONPs) were synthesised through a simple and efficient biogenic synthesis approach, exploiting the reducing and capping potential of Aloe barbadensis Miller (A. vera) leaf extract (ALE). ALE-capped ZnO nanoparticles (ALE-ZnONPs) were characterized using UV-Vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) analyses. XRD analysis provided the average size of ZnONPs as 15 nm. FTIR spectral analysis suggested the role of phenolic compounds, terpenoids and proteins present in ALE, in nucleation and stability of ZnONPs. Flow cytometry and atomic absorption spectrophotometry (AAS) data analyses revealed the surface binding and internalization of ZnONPs in Gram +ve (Staphylococcus aureus) and Gram -ve (Escherichia coli) cells, respectively. Significant antibacterial activity of ALE-ZnONPs was observed against extended spectrum beta lactamases (ESBL) positive E. coli, Pseudomonas aeruginosa, and methicillin resistant S. aureus (MRSA) clinical isolates exhibiting the MIC and MBC values of 2200, 2400 μg/ml and 2300, 2700 μg/ml, respectively. Substantial inhibitory effects of ALE-ZnONPs on bacterial growth kinetics, exopolysaccharides and biofilm formation, unequivocally suggested the antibiotic and anti-biofilm potential. Overall, the results elucidated a rapid, environmentally benign, cost-effective, and convenient method for ALE-ZnONPs synthesis, for possible applications as nanoantibiotics or drug carriers. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Childhood adverse life events, disordered eating, and body mass index in US Military service members.

    PubMed

    Bakalar, Jennifer L; Barmine, Marissa; Druskin, Lindsay; Olsen, Cara H; Quinlan, Jeffrey; Sbrocco, Tracy; Tanofsky-Kraff, Marian

    2018-03-02

    US service members appear to be at high-risk for disordered eating. Further, the military is experiencing unprecedented prevalence of overweight and obesity. US service members also report a high prevalence of childhood adverse life event (ALE) exposure. Despite consistent links between early adversity with eating disorders and obesity, there is a dearth of research examining the association between ALE exposure and disordered eating and weight in military personnel. An online survey study was conducted in active duty personnel to examine childhood ALE history using the Life Stressor Checklist - Revised, disordered eating using the Eating Disorder Examination - Questionnaire total score, and self-reported body mass index (BMI, kg/m 2 ). Among 179 respondents, multiple indices of childhood ALE were positively associated with disordered eating. Traumatic childhood ALE and subjective impact of childhood ALE were associated with higher BMI and these associations were mediated by disordered eating. Findings support evaluating childhood ALE exposure among service members with disordered eating and weight concerns. Moreover, findings support the need for prospective research to elucidate these relationships. © 2018 Wiley Periodicals, Inc.

  9. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction.

    PubMed

    Yu, Zirui; Peldszus, Sigrid; Huck, Peter M

    2009-03-01

    The adsorption of two representative pharmaceutically active compounds (PhACs)-naproxen and carbamazepine and one endocrine disrupting compound (EDC)-nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surface diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol.

  10. A double-blind, randomized, placebo-controlled, single-dose study of the cyclooxygenase-2 inhibitor, GW406381, as a treatment for acute migraine.

    PubMed

    Wentz, A L; Jimenez, T B; Dixon, R M; Aurora, S K; Gold, M

    2008-04-01

    The objective of the present study was to explore the clinical efficacy and tolerability of GW406381, a cyclooxygenase-2 (COX-2) inhibitor with relatively high CNS penetration, in acute migraine. This was a double-blind, single-dose study of GW406381 compared with placebo and naproxen sodium compared with placebo (protocol number CXA20008). Three hundred and thirty-seven subjects were randomized 1:1:1 to GW406381 (70 mg), naproxen sodium (825 mg), or placebo for the treatment of one migraine headache of moderate or severe intensity in a potential 8-week period. The primary end-point was the proportion of subjects with headache relief [reduction in headache severity score from pre-dose 2 (moderate) or 3 (severe) to 0 (no pain) or 1 (mild)] at 2 h post-dose for GW406381 compared with placebo. Significantly higher proportions of subjects treated with GW406381 (50%, P = 0.032) or naproxen sodium (56%, P = 0.005) than with placebo (35%) reported headache relief at 2 h post-dose. Additional significant benefits were observed on many secondary outcomes, including proportions of subjects pain-free, for both GW406381 and naproxen sodium treatment compared with placebo. Both active treatments were well tolerated. Single-dose GW406381 (70 mg) and naproxen sodium (825 mg) were effective and well tolerated in the treatment of acute migraine.

  11. In vitro evaluation of dendrimer prodrugs for oral drug delivery.

    PubMed

    Najlah, Mohammad; Freeman, Sally; Attwood, David; D'Emanuele, Antony

    2007-05-04

    Dendrimer-based prodrugs were used to enhance the transepithelial permeability of naproxen, a low solubility model drug. The stability of the dendrimer-naproxen link was assessed. Naproxen was conjugated to G0 polyamidoamine (PAMAM) dendrimers either by an amide bond or an ester bond. The stability of G0 prodrugs was evaluated in 80% human plasma and 50% rat liver homogenate. The cytotoxicity of conjugates towards Caco-2 cells was determined and the transport of the conjugates across Caco-2 monolayers (37 degrees C) was reported. In addition, one lauroyl chain (L) was attached to the surface group of G0 PAMAM dendrimer of the diethylene glycol ester conjugate (G0-deg-NAP) to enhance permeability. The lactic ester conjugate, G0-lact-NAP, hydrolyzed slowly in 80% human plasma and in 50% rat liver homogenate (t(1/2)=180 min). G0-deg-NAP was hydrolyzed more rapidly in 80% human plasma (t(1/2)=51 min) and was rapidly cleaved in 50% liver homogenate (t(1/2)=4.7 min). The conjugates were non-toxic when exposed to Caco-2 cells for 3h. Permeability studies showed a significant enhancement in the transport of naproxen when conjugated to dendrimers; L-G0-deg-NAP yielding the highest permeability. Dendrimer-based prodrugs with appropriate linkers have potential as carriers for the oral delivery of low solubility drugs such as naproxen.

  12. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction

    SciTech Connect

    Yu, Z.; Peldszus, S.; Huck, P.M.

    The adsorption of two representative pharmaceutically active compounds (PhACs) naproxen and carbamazepine and one endocrine disrupting compound (EDC) nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. The GAC adsorbents were coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surfacemore » diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol. 25 refs., 4 figs., 1 tab.« less

  13. Anti-inflammatory evaluation and characterization of leaf extract of Ananas comosus.

    PubMed

    Kargutkar, Samira; Brijesh, S

    2018-04-01

    Ananas comosus (L.) Merr (Pineapple) is a tropical plant with an edible fruit. In the present study, the potential anti-inflammatory activity of A. comosus leaf extract (ALE) was studied. ALE prepared using soxhlet apparatus was subjected to preliminary qualitative phytochemical analysis and quantitative estimations of flavonoids and tannins. The components present in ALE were identified using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Inhibitory effects of ALE on protein denaturation, and proteinase activity were assessed. Its effect on secretion of pro-inflammatory cytokines and inflammatory mediators by lipopolysaccharide-stimulated macrophages was also analyzed. Further, its anti-inflammatory activity in carrageenan-induced inflammatory rat model was examined. The preliminary qualitative phytochemical analysis revealed presence of flavonoids, phenols, tannins, carbohydrates, glycosides, and proteins in the extract. Total flavonoids and total tannins were 0.17 ± 0.006 mg equivalent of quercetin/g of ALE and 4.04 ± 0.56 mg equivalent of gallic acid/g of ALE. LC-MS analysis identified the presence of 4-hydroxy pelargonic acid, 3,4,5-trimethoxycinnamic and 4-methoxycinnamic acid, whereas GC-MS analysis identified the presence of campesterol and ethyl isoallocholate that have been previously reported for anti-inflammatory activity. ALE showed significant inhibition of protein denaturation and proteinase activity and also controlled secretion of tumour necrosis factor-α, interleukin-1β and prostaglandins, as well as the generation of reactive oxygen species by activated macrophages. ALE also significantly decreased carrageenan-induced acute paw edema. The study, therefore, identified the components present in ALE that may be responsible for its anti-inflammatory activity and thus demonstrated its potential use against acute inflammatory diseases.

  14. The nuclear hormone receptor E75A regulates vitellogenin gene (Al-Vg) expression in the mirid bug Apolygus lucorum.