Thesis (doctoral)--Katholieke Universiteit te Nijmegen.

The purpose was to determine the effect of Naproxen in attenuating the symptoms (muscle soreness level) and signs (plasma CK activity and muscular strength decrement) of delayed onset muscle soreness (DOMS). Twenty subjects were randomly assigned Naproxen (500 mg BID) or placebo in a double-blind, crossover design. Two testing phases, each 8 days in duration, were separated by a washout period of 7 days. Eccentric single-leg exercises were performed on Days 1, 3 and 4 to induce DOMS in the quadriceps muscles. Perception of muscle soreness, plasma CK, and knee extensor torque were evaluated throughout each phase. Following the eccentric exercise, plasma CK levels were similarly elevated in both Naproxen and placebo conditions. After DOMS had developed, Naproxen reduced the perception of soreness on Day 3 when muscle soreness was highest. Following treatments with Naproxen, peak quadriceps torque during leg extension at 60$ sp circ$/s was higher compared to placebo, however at higher velocity (180 and 300$ sp circ$/s) peak muscle torques were similar. The data indicate that therapeutic doses of Naproxen do not prevent CK release into the plasma but decreases the perception of muscle soreness and positively influences quadriceps peak torque.

Erlangen, Nürnberg, Universiẗat, Diss., 2008. / Enth. ausserdem 1 Sonderabdr. aus: International journal of clinical pharmacology and therapeutics ; Vol. 46. 2008. - Beitr. teilw. dt., teilw. engl.

Whilst pressure grows for ‘greener’ solutions to chemical synthesis, biocatalysis offers a cleaner and more efficient way of chemical production using ambient experimental conditions such as temperature and pressure. Biocatalysts can offer a route to enantioselective reactions that can produce pure yields of product. Reductases are capable of carrying out asymmetric reduction of C=C bonds which lead to important chiral compounds from alkenes. Old yellow enzymes were employed in the synthesis of the profen Naproxen by precursors with three different functional groups; nitro, carboxylic acid and methyl ester. Three routes were developed using the three precursors with activity detected with at several OYEs. Reactions towards Naproxen were completed by enzymatic or chemoenzymatic routes. Of particular interest was the direct reduction of 2-(6-methoxynaphthalen-2-yl)acrylate to (R)-Naproxen by OYEs, XenA and GYE. This reaction was run at a 50 mg scale with 85% yield of Naproxen observed. This activity of XenA and GYE towards substrates containing monoacid activating groups is as yet unreported in OYEs and leads the way to expand the biocatalytic potential of this enzyme group. Additional screens were carried out with XenA and GYE with 2-phenylacrylic acid and additional related substrates screened in an attempt to expand the substrate range of the OYEs. However, the only activity detected was that with XenA and 2-phenylacrylic acid, suggesting that XenA and GYE are not active with a wide range of monoacid containing substrates.

Trabajo de Investigación Requisito para optar al Título de Cirujano Dentista / En el presente trabajo, se investigó la actividad analgésica de la coadministracion intraperitoneal de dos AINEs; dexketoprofeno y naproxeno, con distinta selectividad inhibitoria por COX-1. La actividad analgésica de ambos AINEs resultó ser dosis dependiente, siendo de mayor efectividad el dexketoprofeno. Mediante análisi isobolografico se determinó que la coadministracion de ambos produjo una interacción de tipo supraaditiva o sinérgica. Se evaluó la participación de los sistemas opioide y NO/GMPc, en la acción desarrollada por dexketoprofeno y naproxeno, mediante el pretratamiento de los animales con naltrexona y L-NAME. Los resultados muestran que sólo la naltrexona incrementó significativamente la interacción sinérgica de la mezcla, en tanto, L-NAME no la modificó este ensayo experimental del dolor, se concluye que existe una interacción sinérgica entre dexketoprofeno y naproxeno, en la que participa el sistema opioide en la modulación de la actividad antinociceptiva de la mezcla. Este hallazgo es de importancia clínica, por su proyección en el tratamiento farmacológico del dolor.

Trabajo de Investigación Requisito para optar al Título de Cirujano Dentista / El dolor constituye una de las principales causas de consulta odontológica. Entre los múltiples fármacos que existen en la actualidad para el manejo del dolor, sea éste tanto agudo como crónico, los analgésicos antiinflamatorios no esteroidales (AINEs) constituyen una de las herramientas más utilizadas por los profesionales. Considerando que su uso esta asociado a diversos efectos secundarios, se hace necesario buscar métodos para potenciar su efecto analgésico disminuyendo al mismo tiempo los efectos indeseables, siendo el uso combinado de AINEs una estrategia para lograrlo. En el presente trabajo se evaluó la actividad analgésica producida por dos AINEs, dexketoprofeno y naproxeno, en el test de las contorsiones abdominales o writhing test, siendo evaluados en forma aislada y en combinación. Se utilizaron ratones, a los cuales se les administró vía intraperitoneal ambas drogas combinadas en relación 1:1, 1:3 y 3:1 y en proporciones fijas de 1/2, 1/4, 1/8 y 1/16 de las DE25 y DE50 de cada AINE. Se determinó por análisis isobolográfico la naturaleza de la interacción entre ambos, siendo esta de tipo sinérgico, excepto en la combinación 1:3. Este hallazgo tiene importancia clínica, por su proyección en el tratamiento farmacológico del dolor, incidiendo a través de nuevas combinaciones farmacológicas, en un beneficio para los pacientes.

No description available.

Syftet med denna studie var att undersöka hur stor effekt kombinationsbehandling med naproxen och sumatriptan har vid migrän hos vuxna människor jämfört med monoterapi med naproxen eller sumatriptan samt placebo. Studien utformades som en litteraturstudie och sökningar skedde i PubMed via Linnéuniversitetets bibliotek med sökorden ”migraine AND triptan* AND NSAID AND efficacy”, ”migraine AND sumatriptan AND naproxen AND combination AND efficacy” samt ”naproxen AND sumatriptan”. Sökningarna ledde till granskning av 6 studier.     Sammanfattningsvis hade kombinationsbehandlingen statistiskt signifikanta fördelar gällande flera effektmått vid behandling av migrän, bland annat smärtfrihet 2 timmar efter behandling och ihållande smärtfrihet upp till 24 timmar efter behandling, jämfört med såväl monoterapierna som placebo, medan biverkningsrisken inte ökade statistiskt signifikant med kombinationsterapin. Tidigt insättande av behandling, när migränen fortfarande är mild, gav bäst resultat, och effekten kvarstod under flera behandlingstillfällen. Patienter, som behandlades med kombinationsterapin, kunde statistiskt signifikant snabbare återgå till normal funktion i vardagsliv och på arbete, med minskat produktionsbortfall som följd, och de var också nöjdare med kombinationsbehandlingen än med monoterapierna och placebo. Trots dessa resultat blir långt ifrån alla bra. Knappt varannan patient, som behandlas med sumatriptan och naproxen vid mild migrän, är smärtfria efter 2 timmar. Vid måttlig till svår migrän är det ungefär 1 av 3 som är smärtfria 2 timmar efter kombinationsbehandling. Effektivare läkemedel mot migrän är önskvärt. / The purpose of this study was to analyse the efficacy of the combination of naproxen and sumatriptan when used for migraine in adults, and compare with monotherapy with naproxen or sumatriptan and placebo. The study was a literature study and searches were carried out in PubMed via the Linnaeus University library with the keywords ”migraine AND triptan* AND NSAID AND efficacy”, ”migraine AND sumatriptan AND naproxen AND combination AND efficacy” and also ”naproxen AND sumatriptan”. The searches resulted in 6 studies that were reviewed.     In summary, the combination therapy resulted in statistically significant improvements for multiple endpoints in the treatment of migraine, including patients being free of pain 2 hours after treatment and sustained pain-free response up to 24 hours after treatment, compared with both monotherapies and placebo, while the potential for adverse events did not increase statistically significantly with the combination therapy. Early intervention, when migraine was still mild, gave best results, and the effect persisted for several treatment sessions. Patients treated with combination therapy returned statistically significantly faster to normal function in everyday life and at work, with reduced downtime, and they were also more satisfied with the combination therapy than with mono therapy or placebo. Despite this, far from everybody gets well with treatment. Hardly every second patient treated for mild migraine with sumatriptan and naproxen is free from pain after 2 hours and when treating more severe forms of migraine only about 1 in 3 is free from pain after 2 hours. More effective treatments of migraine are needed.

Pharmaceuticals are a group of emerging organic compounds of environmental concern used extensively in human and veterinary medicine. They are continually released into the environment as a result of manufacturing operations and excretion from humans and animals. These compounds enter directly into the municipal sewage systems and into wastewater treatment plants. A large number of important and potentially harmful organic contaminants, such as these pharmaceuticals, are not regulated in drinking and other waters. As a result, conventional technologies at most waste water treatment plants (WWTPs) discharge water that meet regulatory standards, yet are not specifically designed to remove these organic contaminants. Therefore, pharmaceutical compounds and their metabolites remain in discharged effluent and enter into the natural aquatic environment. Concentrations of pharmaceutical residues measured in water are typically reported in the ranges of ug/L to ng/L, which are at least three to four orders of magnitude lower than that required to produce a pharmacological effect. The probability of risks to humans arising from such an acute exposure is unlikely, but the possible effects resulting from life-long exposures and synergistic effects from exposure to many chemicals have yet to be determined. It has been widely reported that pharmaceuticals and their metabolites that enter into the aquatic environment can have a potential harmful effect on the aquatic ecosystem and can reach drinking water sources. This research focuses on non-steroid anti-inflammatory drugs (NSAIDs), a group of pharmaceuticals which are widely used as analgesic, antipyretic and anti-inflammatory agents. NSAIDs are frequently used because they are easily accessible as over the counter medication and are a group of drugs that do not produce addiction, respiratory depression, or drowsiness. There is an incentive for removing NSAIDs and other pharmaceuticals from the aquatic environment. Thus, quantitative evaluation of the fate of pharmaceuticals, proper risk assessment and improvement of the efficiency of WWTPs need sensitive and reliable analytical methods. The purpose of this project was to provide a method for detecting three common NSAIDs, IBF, KTF, and NAP, in purified water with LLE-GC-FID. And, an investigation of UV photolysis, UV/H2O2, and UV/TiO2 AOPs was performed to determine their effectiveness in treating IBF, KTF, and NAP in purified water. All treatment methods were successful in degrading target compounds with a total degradation of 86% or greater after 45 minutes. A liquid-liquid extraction technique using methylene chloride and BSTFA + 1%TMCS derivatizing agent was determined for detecting low concentrations of IBF, KTF, and NAP with calibration curves showing good linearity with all R2 values greater than 0.9880.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of drugs prescribed to relieve pain, fever and inflammation, and are among the most commonly consumed medications in Ontario. Approximately 70% of the ingested dose is excreted unchanged or as an active metabolite, much of which reaches the surface waters of lakes and rivers. NSAIDs function through the inhibition of cyclooxygenase (COX), an enzyme present in two isoforms in the body; the constitutively expressed COX-1 and the inducible COX-2. Traditional NSAIDs like ibuprofen inhibit both isoforms with little selectivity while newer variants such as naproxen preferentially inhibit COX-2. Both COX isoforms share a high similarity between humans and fish creating a potential for off target effects to exposed aquatic organisms. This research investigated the chronic effects of waterborne exposure to 0, 0.1, 1, 10 and 100 μg/L of a nonselective and selective NSAID (ibuprofen and naproxen, respectively) on Florida flagfish (Jordanella floridae) over one complete life-cycle. Chronic exposure concentrations were selected by performing a short term experiment which examined the hatchability of flagfish eggs using continuous semi-static exposure conditions. Growth, survivability and reproductive endpoints were assessed in the life-cycle study. A concentration-response relationship for both NSAIDs was detected during the first 28 days post-hatch, resulting in increased body length for F1 fish and their offspring with increasing concentrations. Exposure to 0.1 μg/L of both ibuprofen and naproxen resulted in a decrease in egg fertilization providing an experimental LOEC (lowest observable effect concentration) of 0.1 ug/L and NOEC (no observable effect concentration) of < 0.1 ug/L for both ibuprofen and naproxen based on the reproductive endpoint. This indicates that either NSAID has the potential to affect the reproductive success of flagfish at concentrations at or below those commonly found in the environment. / UOIT