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Sample records for surrogates ketoprofen doses

  1. Ketoprofen

    Science.gov (United States)

    Prescription ketoprofen is used to relieve pain, tenderness, swelling, and stiffness caused by osteoarthritis (arthritis caused by a breakdown ... swelling of the lining of the joints). Prescription ketoprofen capsules are also used to relieve pain, including ...

  2. A therapeutic dose of ketoprofen causes acute gastrointestinal bleeding, erosions, and ulcers in rats.

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    Shientag, Lisa J; Wheeler, Suzanne M; Garlick, David S; Maranda, Louise S

    2012-11-01

    Perioperative treatment of several rats in our facility with ketoprofen (5 mg/kg SC) resulted in blood loss, peritonitis, and death within a day to a little more than a week after surgery that was not related to the gastrointestinal tract. Published reports have established the 5-mg/kg dose as safe and effective for rats. Because ketoprofen is a nonselective nonsteroidal antiinflammatory drug that can damage the gastrointestinal tract, the putative diagnosis for these morbidities and mortalities was gastrointestinal toxicity caused by ketoprofen (5 mg/kg). We conducted a prospective study evaluating the effect of this therapeutic dose of ketoprofen on the rat gastrointestinal tract within 24 h. Ketoprofen (5 mg/kg SC) was administered to one group of rats that then received gas anesthesia for 30 min and to another group without subsequent anesthesia. A third group was injected with saline followed by 30 min of gas anesthesia. Our primary hypothesis was that noteworthy gastrointestinal bleeding and lesions would occur in both groups treated with ketoprofen but not in rats that received saline and anesthesia. Our results showed marked gastrointestinal bleeding, erosions, and small intestinal ulcers in the ketoprofen-treated rats and minimal damages in the saline-treated group. The combination of ketoprofen and anesthesia resulted in worse clinical signs than did ketoprofen alone. We conclude that a single 5-mg/kg dose of ketoprofen causes acute mucosal damage to the rat small intestine.

  3. Dose-response investigation of oral ketoprofen in pigs challenged with Escherichia coli endotoxin.

    Science.gov (United States)

    Mustonen, K; Banting, A; Raekallio, M; Heinonen, M; Peltoniemi, O A T; Vainio, O

    2012-07-21

    In order to determine the effective dose, the effects of orally administered ketoprofen were evaluated in pigs following intravenous challenge with Escherichia coli endotoxin. One hour after the challenge, five groups of pigs were treated with either tap water or ketoprofen (0.5 mg/kg, 1 mg/kg, 2 mg/kg or 4 mg/kg). The body temperature was measured and a total clinical score was calculated after assessing the general behaviour, respiratory rate and locomotion of the pigs. Thromboxane B(2) and ketoprofen concentrations were analysed from blood samples. Ketoprofen treatment significantly reduced the rectal temperature and total clinical scores, and lowered blood thromboxane B(2) concentrations when compared with the control group. Ketoprofen plasma concentrations were lower than previously reported in healthy pigs after similar doses. The appropriate dose of orally administered ketoprofen in pigs in this model is 2 mg/kg, as the higher dose of 4 mg/kg failed to provide an additional benefit.

  4. Comparison of two doses of ketoprofen to treat pain: a double-blind, randomized, noninferiority trial.

    Science.gov (United States)

    Riou, Bruno; Plaisance, Patrick; Lecomte, François; Soulat, Louis; Orcel, Philippe; Mazoit, Jean-Xavier

    2014-02-01

    The aim of our study was to compare the efficacy and safety of two doses of ketoprofen (200 mg vs. 300 mg/day) in ambulatory emergency patients with pain related to traumatic and nontraumatic bone and joint diseases. We tested the hypothesis that the efficacy of the lower dose was not lower than that of the higher dose in a double-blind, randomized, noninferiority trial. Patients included in the study were aged 18-65 years with closed benign trauma of the motor system or acute noninfectious rheumatologic conditions, with a resting pain intensity ≥3/10 on a numeric pain scale (NPS), requiring ketoprofen for 5 days. The main end-point was based on two efficacy co-criteria: (i) mean change from baseline of resting pain intensity at the end of the day over 5 days and (ii) total intake of concomitant analgesics. We included 409 patients: 200 in the 200-mg group and 209 in the 300-mg group. The mean change in pain intensity at rest (difference between groups: 0.0, 95% CI -0.4 to 0.4; P = 1.00) and in analgesic consumption (difference between groups: -0.6, 95% CI -1.9 to 0.6; P = 0.33) was not significantly different between the two groups, and the differences were lower than the predefined inferiority margins (0.5 and 1.5, respectively), thus demonstrating noninferiority. No significant difference was noted in the incidence of adverse events (21% vs. 20%, P = 0.71). The efficacy of the 200-mg daily dose of ketoprofen in relieving pain in emergency cases was not inferior to that of the 300-mg dose.

  5. Pharmacokinetics of the individual enantiomer S-(+)-ketoprofen after intravenous and oral administration in dogs at two dose levels.

    Science.gov (United States)

    Serrano-Rodríguez, J M; Serrano, J M; Rodríguez, J Morgaz; Machuca, M M Granados; Gómez-Villamandos, R J; Navarrete-Calvo, R

    2014-06-01

    The pharmacokinetic of the individual S-(+)-enantiomer of ketoprofen, S-(+)-ketoprofen, after intravenous (IV) and oral (PO) administration was determined in six dogs at 1 and 3 mg/kg. Plasma concentrations were determined by high performance liquid chromatography with ultraviolet detection. The concentration-time curves were analyzed by non-compartmental methods. Steady-state volume of distribution (Vss) and clearance (Cl) of S-(+)-ketoprofen after IV administration were 0.22 ± 0.07 and 0.19 ± 0.03 L/kg, and 0.10 ± 0.02 and 0.09 ± 0.01 L/h/kg, at 1 and 3 mg/kg, respectively. Following PO administration, S-(+)-ketoprofen achieved maximum plasma concentrations of 4.91 ± 0.76 and 12.47 ± 0.62 μg/ml, at two dose levels, respectively. The absolute bioavailability after PO route was 88.66 ± 12.95% and 85.36 ± 13.90%, respectively.

  6. Ketoprofen Dental Pain Study.

    Science.gov (United States)

    Levin, L M; Cooper, S A; Betts, N J; Wedell, D; Hermann, D G; Lamp, C; Secreto, S A; Hersh, E V

    1997-01-01

    Ketoprofen is a nonsteroidal antiinflammatory drug, recently approved as an over-the-counter (OTC) analgesic at a 12.5 mg dosage strength. This is the first published study which explores the analgesic efficacy and safety of ketoprofen 12.5 mg in patients experiencing pain following the removal of impacted third molars. This study was single-dose, double-blind and randomized utilizing a 6-hour in-patient evaluation period. Patients ingested a single dose of ketoprofen 12.5 mg (n = 30), ketoprofen 37.5 mg (n = 32) or placebo (n = 15) when their post-surgical pain reached at least a moderate intensity on a 5-point categorical (CAT) scale and greater than 50 mm on a 100 mm visual analog scale (VAS). Measures of pain intensity and relief were gathered every 20 minutes for the first 2 hours, and then hourly from hours 3 through 6. Adverse drug reactions were also recorded as they occurred. Both dosages of ketoprofen were significantly more efficacious than placebo (two way ANOVAs, p measures (SPID(VAS), SPID(CAT), TOTPAR) than placebo, with the exception of the 6-hr SPID(CAT) measure for ketoprofen 12.5 mg. No serious side effects were observed in this study. We conclude that ketoprofen in a dose range of 12.5 mg to 37.5 mg is a safe and effective analgesic for the relief of post-operative dental pain.

  7. Ketoprofen overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002661.htm Ketoprofen overdose To use the sharing features on this page, please enable JavaScript. Ketoprofen is a nonsteroidal anti-inflammatory drug. It is ...

  8. Topical ketoprofen patch.

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    Mazières, Bernard

    2005-01-01

    Although oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of a variety of acute and chronic pain conditions, their use may be associated with serious systemic adverse effects, particularly gastrointestinal disorders. In order to minimise the incidence of systemic events related to such agents, topical NSAIDs have been developed. Topical NSAIDs, applied as gels, creams or sprays, penetrate the skin, subcutaneous fatty tissue and muscle in amounts that are sufficient to exert a therapeutic effect on peripheral and central mechanisms in the absence of high plasma concentrations. Data indicate that topical NSAIDs are effective at relieving pain in a number of acute and chronic pain indications. This review article discusses the pharmacokinetics, efficacy and tolerability of a new formulation of ketoprofen available as a topical patch. The topical patch containing ketoprofen 100mg as the active principle has been developed using a novel delivery system that dispenses therapeutic doses of the drug directly to the site of injury. Pharmacokinetic data indicate that although plasma levels of ketoprofen are higher when the drug is administered as a patch versus a gel, the total systemic bioavailability of ketoprofen 100 mg administered via a patch is no more than 10% of that reported for ketoprofen 100 mg administered orally. Because the patch facilitates ketoprofen delivery over a 24-hour period, the drug remains continually present in the tissue subjacent to the site of application. High tissue but low plasma ketoprofen concentrations mean that while tissue concentrations are high enough to exert a therapeutic effect, plasma concentrations remain low enough to not result in systemic adverse events caused by elevated serum NSAID levels. Phase III clinical trials in patients with non-articular rheumatism and traumatic painful soft tissue injuries showed that the topical ketoprofen patch was significantly more effective than placebo at

  9. Comparison of single dose transdermal patches of diclofenac and ketoprofen for postoperative analgesia in lower limb orthopaedic surgery

    Directory of Open Access Journals (Sweden)

    Reetu Verma

    2016-03-01

    Conclusions: Both ketoprofen and diclofenac transdermal patch are effective for postoperative analgesia but less number of patients required rescue analgesic in ketoprofen group. [Int J Res Med Sci 2016; 4(3.000: 718-721

  10. The disposition of ketoprofen enantiomers in man.

    OpenAIRE

    Sallustio, B C; Purdie, Y J; Whitehead, A G; Ahern, M J; Meffin, P J

    1988-01-01

    1. The disposition of ketoprofen enantiomers was studied in 21 patients taking racemic ketoprofen (Orudis SR). 2. In each patient the plasma concentrations of the R- and S-enantiomers were similar at all times over a 24 h dosing interval. The mean (+/- s.e. mean) time-averaged plasma ketoprofen concentrations over the dosage interval were 0.76 (+/- 0.06) mg l-1 for R-ketoprofen and 0.78 (+/- 0.06) mg l-1 for S-ketoprofen. 3. Creatinine clearances for the 21 patients ranged from 6-162 ml min-1...

  11. Isobolographic analysis of the antinociceptive interactions between ketoprofen and paracetamol.

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    Qiu, Hai-Xia; Liu, Jin; Kong, Hui; Liu, Yan; Mei, Xing-Guo

    2007-02-28

    The present study was undertaken to evaluate the antinociceptive interaction between paracetamol and ketoprofen. The antinociceptive effect of oral administration of the drugs alone or in combination was evaluated using the mouse abdominal constriction test. The data were interpreted by isobolographic analysis to establish the nature of the interaction. The effective dose that produced 50% antinociception (ED(50,mix)) was calculated from the log dose-response curve of fixed-ratio combinations of paracetamol with ketoprofen. This ED(50,mix) was compared to the theoretical additive ED(50,add) by isobolographic analysis. The experimental ED(50,mix) was found to be significantly smaller than the theoretically calculated ED(50,add), indicating a synergistic antinociceptive interaction between ketoprofen and paracetamol. Pharmacokinetic studies were carried out with mice treated with combined ketoprofen (12 mg/kg) and paracetamol (36 mg/kg). Plasma levels of ketoprofen were not changed by concurrent paracetamol treatment, and similarly no statistically significant difference was observed between paracetamol alone and the combination with ketoprofen. The pharmacokinetic analysis revealed that the combination of ketoprofen with paracetamol exerted a synergistic (supra-additive) interaction that was not associated with a pharmacokinetic interaction. The results of this study demonstrate significant synergism between ketoprofen and paracetamol.

  12. Radiation sterilization of ketoprofen

    Energy Technology Data Exchange (ETDEWEB)

    Katusin-Razem, Branka [Ruder Boskovic Institute, P.O.B 180, Zagreb 10000 (Croatia)]. E-mail: brazem@irb.hr; Hamitouche, Katia [Centre de Recherche et Developpement Saidal, El Harrach (Algeria); Maltar-Strmecki, Nadica [Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000 (Croatia); Kos, Karmen [Belupo Pharmaceutical Works, Koprivnica 48000 (Croatia); Pucic, Irina [Ruder Boskovic Institute, P.O.B 180, Zagreb 10000 (Croatia); Britvic-Budicin, Smiljana [Ruder Boskovic Institute, P.O.B 180, Zagreb 10000 (Croatia); Razem, Dusan [Ruder Boskovic Institute, P.O.B 180, Zagreb 10000 (Croatia)

    2005-06-01

    Radiation sterilization of ketoprofen (KP) dry powder was investigated by selected physico-chemical methods. High-performance liquid chromatography, ultraviolet spectrophotometry, infrared spectrophotometry, differential scanning calorimetry, X-ray diffraction and electron spin resonance spectroscopy did not show any significant degradation at sterilization dose 25 kGy. To determine the nature, extent and direction of radiation-induced changes, KP was irradiated to extremely high doses, much higher than necessary to achieve sterility. The irradiated KP did not show any difference of XRD patterns up to 200 kGy; with DSC and IR some changes were detected only above 1000 and 2000 kGy, respectively; HPLC has shown about 5% destruction at 2000 kGy. Acetyl benzophenon (AcBph) was generated by irradiation with G(AcBph)=(1.6{+-}0.1)x10{sup -8} mol J{sup -1}. Ames test has shown no mutagenicity of KP irradiated with 3000 kGy or of the oily mixture of radiolytic products isolated from it. Solid KP has proven to be very stable on irradiation, and irradiation has been found to be a suitable method for its sterilization.

  13. Radiation sterilization of ketoprofen

    Science.gov (United States)

    Katušin-Ražem, Branka; Hamitouche, Katia; Maltar-Strmečki, Nadica; Kos, Karmen; Pucić, Irina; Britvić-Budicin, Smiljana; Ražem, Dušan

    2005-06-01

    Radiation sterilization of ketoprofen (KP) dry powder was investigated by selected physico-chemical methods. High-performance liquid chromatography, ultraviolet spectrophotometry, infrared spectrophotometry, differential scanning calorimetry, X-ray diffraction and electron spin resonance spectroscopy did not show any significant degradation at sterilization dose 25 kGy. To determine the nature, extent and direction of radiation-induced changes, KP was irradiated to extremely high doses, much higher than necessary to achieve sterility. The irradiated KP did not show any difference of XRD patterns up to 200 kGy; with DSC and IR some changes were detected only above 1000 and 2000 kGy, respectively; HPLC has shown about 5% destruction at 2000 kGy. Acetyl benzophenon (AcBph) was generated by irradiation with G(AcBph)=(1.6±0.1)×10 -8 mol J -1. Ames test has shown no mutagenicity of KP irradiated with 3000 kGy or of the oily mixure of radiolytic products isolated from it. Solid KP has proven to be very stable on irradiation, and irradiation has been found to be a suitable method for its sterilization.

  14. Função renal de cães tratados com doses terapêuticas de flunixin meglumine e ketoprofen durante o trans e pós-operatório Renal function in dogs treated with therapeutic dosages of flunixin meglumine and ketoprofen during the trans and pos-operatory period

    Directory of Open Access Journals (Sweden)

    Deila Schossler

    2001-03-01

    Full Text Available Baseando-se em relatos de casos de falência renal após a administração de flunixin meglumine em animais saudáveis, o presente trabalho foi desenvolvido visando avaliar a função renal através da medição sérica de uréia e creatinina de quatro grupos de cinco caninos submetidos a um procedimento cirúrgico, sendo os dois primeiros tratados com flunixin meglumine e os dois seguintes tratados com ketoprofen, ambos em doses terapêuticas. Os valores séricos de uréia e creatinina mantiveram-se dentro dos limites fisiológicos, permitindo concluir que não há lesão renal em consequência da utilização tanto no trans quanto no pós-operatório de animais clinicamente sadios.It has been reported in the literature several clinical cases of renal failure after the use of flunixin meglumine in normal healthy dogs. Based on these reports this study was developed to evaluate the renal function of normal healthy dogs. Blood urea nitrogen (BUN and serum creatinine were measured in four groups of 5 dogs submitted to a single surgical procedure. Two groups received flunixin meglumine and the other two ketoprofen, both in therapeutic dosages. The results showed values of BUN and serum creatinine within normal range for dogs. It is fair to conclude that flunixin meglumine and ketoprofen do not produce renal failure when administered during the peri-operative period in normal healthy dogs.

  15. Topical ketoprofen nanogel: artificial neural network optimization, clustered bootstrap validation, and in vivo activity evaluation based on longitudinal dose response modeling.

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    Elkomy, Mohammed H; Elmenshawe, Shahira F; Eid, Hussein M; Ali, Ahmed M A

    2016-11-01

    This work aimed at investigating the potential of solid lipid nanoparticles (SLN) as carriers for topical delivery of Ketoprofen (KP); evaluating a novel technique incorporating Artificial Neural Network (ANN) and clustered bootstrap for optimization of KP-loaded SLN (KP-SLN); and demonstrating a longitudinal dose response (LDR) modeling-based approach to compare the activity of topical non-steroidal anti-inflammatory drug formulations. KP-SLN was fabricated by a modified emulsion/solvent evaporation method. Box-Behnken design was implemented to study the influence of glycerylpalmitostearate-to-KP ratio, Tween 80, and lecithin concentrations on particle size, entrapment efficiency, and amount of drug permeated through rat skin in 24 hours. Following clustered bootstrap ANN optimization, the optimized KP-SLN was incorporated into an aqueous gel and evaluated for rheology, in vitro release, permeability, skin irritation and in vivo activity using carrageenan-induced rat paw edema model and LDR mathematical model to analyze the time course of anti-inflammatory effect at various application durations. Lipid-to-drug ratio of 7.85 [bootstrap 95%CI: 7.63-8.51], Tween 80 of 1.27% [bootstrap 95%CI: 0.601-2.40%], and Lecithin of 0.263% [bootstrap 95%CI: 0.263-0.328%] were predicted to produce optimal characteristics. Compared with profenid® gel, the optimized KP-SLN gel exhibited slower release, faster permeability, better texture properties, greater efficacy, and similar potency. SLNs are safe and effective permeation enhancers. ANN coupled with clustered bootstrap is a useful method for finding optimal solutions and estimating uncertainty associated with them. LDR models allow mechanistic understanding of comparative in vivo performances of different topical formulations, and help design efficient dermatological bioequivalence assessment methods.

  16. Efficiency of postoperative pain management after gynecologic oncological surgeries with the use of morphine + acetaminophen + ketoprofen versus morphine + metamizol + ketoprofen.

    Science.gov (United States)

    Samulak, D; Michalska, M; Gaca, M; Wilczak, M; Mojs, E; Chuchracki, M

    2011-01-01

    Surgical treatment used in gynecological oncology involves acute postoperative pain which requires efficient treatment. This study covered a group of 128 patients who were randomly divided into two groups. In the postoperative period patients in group I were administered morphine subcutaneously, acetaminophen intravenously and naproxen per rectum. The pain intensity level was checked by means of the pain intensity numeric rating scale (NRS). In the instances of pain rated at 5 or more, patients were additionally administered ketoprofen intravenously. Patients in group II were administered morphine, naproxen, and metamizole instead of acetaminophen and ketoprofen additionally. In group I after the administration of morphine and acetaminophen 22 patients (34.37%) needed additional doses of ketoprofen. In group II 33 women (51.56%) required ketoprofen after the administration of morphine and metamizole (N1 = 22 vs N2 = 33, p metamizol with morphine (without ketoprofen) gave worse analgesic results than acetaminophen with morphine, but the combination of morphine, acetaminophen and ketoprofen or morphine, metamizol and ketoprofen gave satisfactory analgesic results.

  17. Radiation induced degradation of ketoprofen in dilute aqueous solution

    Science.gov (United States)

    Illés, Erzsébet; Takács, Erzsébet; Dombi, András; Gajda-Schrantz, Krisztina; Gonter, Katalin; Wojnárovits, László

    2012-09-01

    The intermediates and final products of ketoprofen degradation were investigated in 0.4 mmol dm-3 solution by pulse radiolysis and gamma radiolysis. For observation of final products UV-vis spectrophotometry and HPLC separation with diode array detection were used, and for identification MS was used. The reactions of •OH lead to hydroxycyclohexadienyl type radical intermediates, in their further reactions hydroxylated derivatives of ketoprofen form as final products. The hydrated electron is scavenged by the carbonyl oxygen and the electron adduct protonates to ketyl radical •OH is more effective in decomposing ketoprofen than hydrated electron. Chemical oxygen demand and total organic carbon content measurements on irradiated aerated solutions showed that using irradiation technology ketoprofen can be mineralised. The initial toxicity of the solution monitored by the Daphnia magna test steadily decreases with irradiation. Using 5 kGy dose no toxicity of the solution was detected with this test.

  18. Limitations in dose-response and surrogate species methodologies for risk assessment of Cry toxins on arthropod natural enemies.

    Science.gov (United States)

    Paula, Débora P; Andow, David A; Bellinati, André; Timbó, Renata Velozo; Souza, Lucas M; Pires, Carmen S S; Sujii, Edison R

    2016-04-01

    Dose-response assays and surrogate species are standard methods for risk analysis for environmental chemicals. These assume that individuals within a species have unimodal responses and that a surrogate species can predict responses of other related taxa. We exposed immature individuals of closely related aphidophagous coccinellid predators, Cycloneda sanguinea and Harmonia axyridis, to Cry1Ac and Cry1F toxins through uniform and constant artificial tritrophic exposure through Myzus persicae aphids. Both toxins were detected in coccinellid pupae, with individual and interspecific variation. Uptake was significantly higher in H. axyridis than in C. sanguinea, both in the proportion of individuals and the concentrations per individual. We also observed bimodal uptake of the Cry toxins by H. axyridis, which indicated that some individuals had low bioaccumulation and some had high bioaccumulation. This suggests that standard dose-response assays need to be interpreted with caution and future assays should examine the modality of the responses. In addition, the similarity in the biological effects of the Cry toxins in the two predators was due to different biological exposure mechanisms. The majority of H. axyridis were exposed both internally and in the gut, while C. sanguinea was exposed primarily in the gut. Thus, despite their close phylogenetic relatedness, these species would not be good surrogates for each other and the surrogate species methodology should be tested more rigorously.

  19. Função renal de cães tratados com doses terapêuticas de flunixin meglumine e ketoprofen durante o trans e pós-operatório

    OpenAIRE

    Deila Schossler; Marcelo Meller Alievi; Mauren Picada Emanuelli; João Eduardo Schossler

    2001-01-01

    Baseando-se em relatos de casos de falência renal após a administração de flunixin meglumine em animais saudáveis, o presente trabalho foi desenvolvido visando avaliar a função renal através da medição sérica de uréia e creatinina de quatro grupos de cinco caninos submetidos a um procedimento cirúrgico, sendo os dois primeiros tratados com flunixin meglumine e os dois seguintes tratados com ketoprofen, ambos em doses terapêuticas. Os valores séricos de uréia e creatinina mantiveram-se dentro ...

  20. Relationship between blood levels and the anti-hyperalgesic effect of ketoprofen in the rat.

    Science.gov (United States)

    Aguilar-Carrasco, José Carlos; Rodríguez-Silverio, Juan; Jiménez-Andrade, Juan Miguel; Carrasco-Portugal, Miriam del Carmen; Flores-Murrieta, Francisco Javier

    2014-05-01

    The relationship between blood levels of ketoprofen and its anti-hyperalgesic effects was examined in rat using the carrageenan-evoked thermal hyperalgesia model. Female adult Wistar rats were injected with carrageenan into the plantar surface of the right hind paw. Immediately after, rats were administered with ketoprofen po and hindpaw withdrawal latency measured and micro-whole blood samples were obtained over six hours via a cannula inserted in the caudal artery. Ketoprofen levels were measured by HPLC. Ketoprofen concentration increased in a dose-dependent manner and was reflected in dose-dependent anti-hyperalgesic effect. The pharmacokinetic and pharmacodynamic parameters expressed as mean ± s.e.m. following administration of 1, 3.2, and 10 mg/kg ketoprofen were: Cmax 1.27 ± 0.08, 3.44 ± 0.20 and 11.76 ± 0.81 μg/mL; AUClast 4.16 ± 0.17, 11.63 ± 0.65 and 28.15 ± 1.32 μg h/mL; and Emax observed (AUCE ): 65.41 ± 7.79, 92.06 ± 6.46 and 98.42 ± 7.53%. A direct relationship between blood concentrations and the anti-hyperalgesic effect of ketoprofen followed a maximum effect model equation. The results indicate that the anti-hyperalgesic effect of ketoprofen in the carrageenan pain model can be predicted by the pharmacokinetic properties of ketoprofen.

  1. Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

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    Mustonen Katja

    2012-09-01

    Full Text Available Abstract Background Ketoprofen is a non-steroidal anti-inflammatory drug which has been widely used for domestic animals. Orally administered racemic ketoprofen has been reported to be absorbed well in pigs, and bioavailability was almost complete. The objectives of this study were to analyze R- and S-ketoprofen concentrations in plasma after oral (PO and intra muscular (IM routes of administration, and to assess the relative bioavailability of racemic ketoprofen for both enantiomers between those routes of administration in growing pigs. Methods Eleven pigs received racemic ketoprofen at dose rates of 4 mg/kg PO and 3 mg/kg IM in a randomized, crossover design with a 6-day washout period. Enantiomers were separated on a chiral column and their concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated and relative bioavailability (Frel was determined for S and R –ketoprofen. Results S-ketoprofen was the predominant enantiomer in pig plasma after administration of the racemic mixture via both routes. The mean (± SD maximum S-ketoprofen concentration in plasma (7.42 mg/L ± 2.35 in PO and 7.32 mg/L ± 0.75 in IM was more than twice as high as that of R-ketoprofen (2.55 mg/L ± 0.99 in PO and 3.23 mg/L ± 0.70 in IM, and the terminal half-life was three times longer for S-ketoprofen (3.40 h ± 0.91 in PO and 2.89 h ± 0.85 in IM than R-ketoprofen (1.1 h ± 0.90 in PO and 0.75 h ± 0.48 in IM. The mean (± SD relative bioavailability (PO compared to IM was 83 ± 20% and 63 ± 23% for S-ketoprofen and R-ketoprofen, respectively. Conclusions Although some minor differences were detected in the ketoprofen enantiomer concentrations in plasma after PO and IM administration, they are probably not relevant in clinical use. Thus, the pharmacological effects of racemic ketoprofen should be comparable after intramuscular and oral routes of

  2. Biomarkers and surrogate endpoints for normal-tissue effects of radiation therapy: the importance of dose-volume effects

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    Bentzen, Søren M.; Parliament, Matthew; Deasy, Joseph O.; Dicker, Adam; Curran, Walter J.; Williams, Jacqueline P.; Rosenstein, Barry S.

    2012-01-01

    Biomarkers are of interest for predicting or monitoring normal tissue toxicity of radiation therapy. Advances in molecular radiobiology provide novel leads in the search for normal tissue biomarkers with sufficient sensitivity and specificity to become clinically useful. This paper reviews examples of studies of biomarkers as predictive markers, as response markers or as surrogate endpoints for radiation side-effects. Single nucleotide polymorphisms (SNPs) are briefly discussed in the context of candidate gene and genome wide association studies. The importance of adjusting for radiation dose distribution in normal tissue biomarker studies is underlined. Finally, research priorities in this field are identified and discussed. PMID:20171510

  3. Comparative assessment of effectiveness of ketoprofen and ketoprofen/beta-cyclodextrin complex in two experimental models of inflammation in rats.

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    Grecu, Mariana; Năstasă, Valentin; Ilie, Cornelia; Miron, Liviu; Mareş, Mihai

    2014-01-01

    Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) can lead to adverse effects such as gastrointestinal distress. The complexation of different groups of active substances with β-cyclodextrin (β-CD) has drawn considerable interest over recent years. The purpose of this study was to analyze the ketoprofen/β-cyclodextrin (K/β-CD) conjugate complex as well as to assess its anti-inflammatory effect after oral administration (doses of 30 mg/m(2) and 15 mg/m(2) of body surface), compared with ketoprofen. The studies were done on two models of experimentally-induced acute inflammation in rats (n = 48, 6/group), by means of intraplantar administration of a 10% aqueous kaolin suspension and intraperitoneal administration of a 1% sodium thioglycolate solution. The dynamics of the acute inflammatory process and the anti-inflammatory effects were monitored using plethysmometric determinations after 3, 6, 9, 12, 24 and 48 h (plantar inflammation), and the absorbance of the exudates (spectrophotometrically read) and nucleated cell counts after 24 h (peritoneal inflammation). The coupling of ketoprofen with β-CD resulted in increased solubility (100% in 60 min) of the newly-formed product, which further resulted in a higher bioavailability compared with ketoprofen (ketoprofen.

  4. Development and Evaluation of Ketoprofen Acrylic Transdermal ...

    African Journals Online (AJOL)

    increased with increase in the ketoprofen content of the adhesive matrix. Inclusion of terpenes in ... literature [6-8], better systems that would result in improved ... Table 1: Composition of the ketoprofen transdermal patches. Ingredient (g). F1.

  5. 21 CFR 522.1225 - Ketoprofen solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketoprofen solution. 522.1225 Section 522.1225... Ketoprofen solution. (a) Specifications. Each milliliter of sterile aqueous solution contains 100 milligrams of ketoprofen. (b) Sponsor. See 000856 in 21 CFR 510.600(c) of this chapter. (c) Conditions of use...

  6. Possible surrogate marker for an effective dose-dense chemotherapy in treating ovarian cancer

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    Chueh-Yi Huang

    2016-06-01

    Conclusion: Lower PLR or lower NLR had better treatment response for dose-dense chemotherapy and are possible markers for representing treatment response in dose-dense chemotherapy. For a clinician, this is useful for timing when to switch to another chemotherapy regimen.

  7. Dose and Size-Dependent Antiviral Effects of Silver Nanoparticles on Feline Calicivirus, a Human Norovirus Surrogate.

    Science.gov (United States)

    Bekele, Aschalew Z; Gokulan, Kuppan; Williams, Katherine M; Khare, Sangeeta

    2016-05-01

    Silver nanoparticles (AgNPs) as antibacterial agents are incorporated in many consumer products, while the use as antiviral agents is an ongoing area of research. We evaluated the antiviral properties of AgNPs of variable sizes (10, 75, and 110 nm) and doses (25, 50, and 100 μg/mL) at different contact time points against feline calicivirus (FCV), a surrogate for norovirus. Antiviral effects of the AgNPs were determined by comparing the infectivity of FCV, the appearance of cytopathic effects (CPEs), and the integrity of the viral capsid protein in viral suspension treated with AgNPs with the untreated controls. The 10 nm AgNPs at 50 and 100 μg/mL concentrations inactivated the FCV beyond the limit of detection, resulting in a decrease of up to 6.5 log10 viral titer, prevented development of CPEs, and reduction in the western blot band signal of the viral capsid protein. No significant antiviral effect was observed for the 75 and 110 nm AgNPs. Conclusions and Applications: These results demonstrate that the antiviral effects of AgNPs are both size and dose dependent, thus potential applications of AgNPs as antiviral agents to prevent contamination of foodborne viruses need to consider size and dose effects.

  8. Cerebrospinal fluid concentrations of vincristine after bolus intravenous dosing - A surrogate marker of brain penetration

    NARCIS (Netherlands)

    Kellie, SJ; Barbaric, D; Koopmans, P; Earl, J; Carr, DJ

    2002-01-01

    BACKGROUND. Vincristine (VCR) is used widely in oncology practice, and regular dosing is commonly associated with the development of sensorimotor or autonomic neuropathies. However, the incidence of VCR-related central nervous system (CNS) toxicity is comparatively low, suggesting that the blood-bra

  9. Cerebrospinal fluid concentrations of vincristine after bolus intravenous dosing: a surrogate marker of brain penetration.

    NARCIS (Netherlands)

    Kellie, S.J.; Barbaric, D.; Koopmans † , P.P.; Earl, J.; Carr, D.J.; Graaf, S.S.N. de

    2002-01-01

    BACKGROUND: Vincristine (VCR) is used widely in oncology practice, and regular dosing is commonly associated with the development of sensorimotor or autonomic neuropathies. However, the incidence of VCR-related central nervous system (CNS) toxicity is comparatively low, suggesting that the blood-bra

  10. Ketoprofen and antinociception in hypo-oestrogenic Wistar rats fed on a high sucrose diet.

    Science.gov (United States)

    Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; García-Martínez, Betzabeth Anali; López-Muñoz, Francisco Javier

    2016-10-05

    Non-steroidal anti-inflammatory drugs such as ketoprofen are the most commonly used analgesics for the treatment of pain. However, no studies have evaluated the analgesic response to ketoprofen in conditions of obesity. The aim of this study was to analyse the time course of nociceptive pain in Wistar rats with and without hypo-oestrogenism on a high sucrose diet and to compare the antinociceptive response using ketoprofen. Hypo-oestrogenic and naïve rats received a hyper caloric diet (30% sucrose) or water ad libitum for 17 weeks, the thermal nociception ("plantar test" method) and body weight were tested during this period. A biphasic response was observed: thermal latency decreased in the 4th week (hyperalgesia), while from 12th to 17th week, thermal latency increased (hypoalgesia) in hypo-oestrogenic rats fed with high sucrose diet compared with the hypo-oestrogenic control group. At 4th and 17th weeks, different doses of ketoprofen (1.8-100mg/kg p.o.), were evaluated in all groups. The administration of ketoprofen at 4th and 17th weeks showed dose-dependent effects in the all groups; however, a greater pharmacological efficacy was observed in the 4th week in the hypo-oestrogenic animals that received sucrose. Nevertheless, in all the groups significantly diminish the antinociceptive effects in the 17th week. Our data showed that nociception was altered in the hypo-oestrogenic animals that were fed sucrose (hyperalgesia and hypoalgesia). Ketoprofen showed a dose-dependent antinociceptive effect at both time points. However, hypo-oestrogenism plus high-sucrose diet modifies the antinociceptive effect of ketoprofen.

  11. Kapasitas Jerap Niosom Terhadap Ketoprofen dan Perdiksi Penggunaan Transdermal

    OpenAIRE

    Rahman, Latifah; Ismail, Isriani; Wahyudin, Elly

    2013-01-01

    Niosom adalah system vesikel yang dapat digunakan sebagai pembawa obat lipofilik, hidrofilik dan ampifilik. Ketoprofen adalah salah satu golongan AINS yang sangat sukar larut dalam air dan dapat menyebabkan iritasi lambung pada penggunaan oral. System penghantaran obat secara transdermal sangat penting dikembangkan untuk ketoprofen. Penelitian ini bertujuan untuk memformulasi niosom yang dapat menjerap ketoprofen secara optimal dan dapat menghantarkan ketoprofen melalui rute pemberian transde...

  12. Ketoprofen sodium: preparation and its formation of mixed crystals with ketoprofen.

    Science.gov (United States)

    Hildebrand, G E; Müller-Goymann, C C

    1997-07-01

    A simple two-step process for the preparation of ketoprofen sodium was developed. The procedure involved dissolution of ketoprofen in ethanolic NaOH followed by evaporation of the solvent. The resulting amorphous solid was crystallized by controlled precipitation from 96% ethanol. The sodium salt proved to be stable for 4 years and its aqueous solutions for at least 1 year (investigated period). Ketoprofen sodium appears to be an alternative bulk form to ketoprofen acid for production of formulations after further characterization of the compound.

  13. Interaction of ketoprofen and frusemide in man.

    OpenAIRE

    Wa, T. C.; Lawson, M; Jackson, S. H.; Hitoglou-Makedou, A.; Turner, P

    1991-01-01

    The effects of ketoprofen on frusemide-induced diuresis, natriuresis and renin release were studied in 12 healthy male volunteers. Each received frusemide 40 mg once daily with either ketoprofen 100 mg twice daily or placebo for two periods of 5 days separated by a treatment-free period according to a randomized, double-blind, cross-over study design. Ketoprofen significantly reduced frusemide-induced diuresis on Day 1 but not on Day 5 of treatment. The natriuresis induced by frusemide on Day...

  14. In vitro percutaneous absorption of ketoprofen and testosterone: comparison of pluronic lecithin organogel vs. pentravan cream.

    Science.gov (United States)

    Lehman, Paul A; Raney, Sam G

    2012-01-01

    An in vitro human percutaneous absorption study was conducted to assess the delivery of ketoprofen and testosterone from two base formulations, a Pluronic lecithin organogel and Pentravan Cream. Each formulation was applied to ex vivo human trunk skin (from three skin donors) on triplicate sections mounted onto Franz Diffusion Cells. Following a 5-mcL/cm2 applied dose, serial dermal receptor solutions were collected over 48 hours. For both compounds, a greater rate and extent of absorption was found from the Pentravan formulation than from the Pluronic lecithin organogel formulation: 3.8-fold greater for ketoprofen, 1.7-fold greater for testosterone, for amount absorbed.

  15. S-Ketoprofen Inhibits Tenotomy-Induced Bone Loss and Dynamics in Weanling Rats

    Science.gov (United States)

    Zeng, Q. Q.; Jee, W. S. S.; Ke, H. Z.; Wechter, W. J.

    1993-01-01

    The objects of this study were to determine whether S-ketoprofen, a non-steroidal anti-inflammatory drug (NSAID), can prevent immobilization (tenotomy)-induced bone loss in weanling rats. Forty five 4 week-old Sprague-Dawley female rats were either sham-operated or subjected to knee tenotomy and treated simultaneously with 0, 0.02, 0.1, 0.5 or 2.5 mg of S-ketoprofen/kg per day for 21 days. We then studied double-fluorescent labeled proximal tibial longitudinal sections and tibial shaft cross sections using static and dynamic histomorphometry. Less cancellous bone mass in proximal tibial metaphyses was found in tenotomized controls than in basal (36%) and sham-operated (54%) controls. This was due to the inhibition of age-related bone gain and induced bone loss due to increased bone resorption and decreased bone formation. S-ketoprofen prevented both the inhibition of age-related bone gain and the stimulation of bone loss at the 2.5 mg/kg per day dose level, while it only prevented bone loss at the 0.5 mg/kg dose levels. In cancellous bone, dynamic histomorphometry showed that S-ketoprofen prevented the tenotomy induced decrease in bone formation and increase in bone resorption. In the tibial shaft, tenotomy inhibited the enlargement of total tissue area by depressing periosteal bone formation, and thus inhibited age-related cortical bone gain. S-ketoprofen treatment did not prevent this change at all dose levels, but reduced marrow cavity area to increase cortical bone area at the 0.1, 0.5 and 2.5 mg/kg per dose levels compared to tenotomy controls. However, the cortical bone area in the 0.1 and 0.5 mg dose-treated treated tenotomy rats was still lower than in the age-related controls. S-ketoprofen also prevented the increase in endocortical eroded perimeter induced by tenotomy. In summary, tenotomy inhibited age-related bone gain and stimulated bone loss in cancellous bone sites, and only inhibited age-related bone gain in cortical bone sites. S-ketoprofen

  16. Ketoprofen-induced formation of amino acid photoadducts: possible explanation for photocontact allergy to ketoprofen.

    Science.gov (United States)

    Karlsson, Isabella; Persson, Elin; Ekebergh, Andreas; Mårtensson, Jerker; Börje, Anna

    2014-07-21

    Photocontact allergy is a well-known side effect of topical preparations of the nonsteroidal anti-inflammatory drug ketoprofen. Photocontact allergy to ketoprofen appears to induce a large number of photocross allergies to both structurally similar and structurally unrelated compounds. Contact and photocontact allergies are explained by structural modification of skin proteins by the allergen. This complex is recognized by the immune system, which initiates an immune response. We have studied ketoprofen's interaction with amino acids to better understand ketoprofen's photoallergenic ability. Irradiation of ketoprofen and amino acid analogues resulted in four different ketoprofen photodecarboxylation products (6-9) together with a fifth photoproduct (5). Dihydroquinazoline 5 was shown to be a reaction product between the indole moiety of 3-methylindole (Trp analogue) and the primary amine benzylamine (Lys analogue). In presence of air, dihydroquinazoline 5 quickly degrades into stable quinazolinone 12. The corresponding quinazolinone (17) was formed upon irradiation of ketoprofen and the amino acids N-acetyl-l-Trp ethyl ester and l-Lys ethyl ester. The formation of these models of an immunogenic complex starts with the ketoprofen-sensitized formation of singlet oxygen, which reacts with the indole moiety of Trp. The formed intermediate subsequently reacts with the primary amino functionality of Lys, or its analogue, to form a Trp-Lys adduct or a mimic thereof. The formation of a specific immunogenic complex that does not contain the allergen but that can still induce photocontact allergy would explain the large number of photocross allergies with ketoprofen. These allergens do not have to be structurally similar as long as they can generate singlet oxygen. To the best of our knowledge, there is no other suggested explanation for ketoprofen's photoallergenic properties that can account for the observed photocross allergies. The formation of a specific immunogenic

  17. The safety of ketoprofen in different ages

    Directory of Open Access Journals (Sweden)

    Claudia Carbone

    2013-01-01

    Full Text Available Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID, which acts by blocking cyclooxygenase (COX 1 and 2, an enzyme involved in the production of prostaglandins, messengers in the development of inflammation. All NSAIDs reduce signs of inflammation by blocking this enzyme and therefore prostaglandin production. In Calabria, 3.69% of adverse drug reactions (ADRs reported in the National Network of Pharmacovigilance concerns the use of ketoprofen; only in one case in which the patient was under the age of 12 years, hospitalization was required for severe episode of pancreatitis. In Italy, Ketoprofen is the 6 th drug for ADRs incidence (560 ADRs in the year 2012, of which, 31% are severe. Despite the high rate of spontaneous reporting, it must be considered that ketoprofen is one of the most used NSAIDs; therefore, as it happens for other commonly used drugs (eg, amoxicillin, the total number of ADRs should be related to the therapeutic use. However, it remains the problem of fragile patients (eg, children and the safety of the drug in different ages. This paper presents a retrospective study on 2012 ADRs reviewing literature on the safety of ketoprofen in the elderly, children, and during pregnancy.

  18. In vivo evaluation of matrix pellets containing nanocrystalline ketoprofen.

    Science.gov (United States)

    Vergote, G J; Vervaet, C; Van Driessche, I; Hoste, S; De Smedt, S; Demeester, J; Jain, R A; Ruddy, S; Remon, J P

    2002-06-20

    The aim of this study was to evaluate the in-vivo behaviour of matrix pellets formulated with nanocrystalline ketoprofen after oral administration to dogs. No significant differences in AUC-values were seen between pellet formulations containing nanocrystalline or microcrystalline ketoprofen and a commercial ketoprofen formulation (reference: Rofenid 200 Long Acting). C(max) of the formulations containing nano- or microcrystalline ketoprofen was significantly higher compared to reference, whereas t(max) was significantly lower. The in-vivo burst release observed for the spray dried nanocrystalline ketoprofen matrix pellets was reduced following compression of the pellets in combination with placebo wax/starch pellets. These matrix tablets sustained the ketoprofen plasma concentrations during 5.6 and 5.4 h for formulations containing nano- and microcrystalline ketoprofen, respectively.

  19. Bioavailability of ketoprofen from orally administered ketoprofen-dextran ester prodrugs in the pig

    DEFF Research Database (Denmark)

    Larsen, C.; Jensen, Bodil Hamborg; Olesen, H. P.

    1991-01-01

    The bioavailability of ketoprofen after oral administration of aqueous solutions of various ketoprofen-dextran ester prodrugs in pigs was assessed. Conjugates derived from dextran fractions in the molecular weight range 10,000-500,000 were employed. Compared to the administration of an oral......-dextran esters. Thus, the present study adds support to a more versatile application of the dextran ester prodrug approach to providing selective colon delivery of drugs possessing a carboxylic acid functional group....

  20. Inclusion complexes of Ketoprofen with β-cyclodextrins: Oral pharmacokinetics of Ketoprofen in human

    Directory of Open Access Journals (Sweden)

    Tayade P

    2006-01-01

    Full Text Available The inclusion behavior of hydroxypropyl b-cyclodextrin and natural b-cyclodextrin was studied toward ketoprofen, in order to develop a new oral dosage form with enhanced dissolution rate and bioavailability, and to study the oral pharmacokinetics of ketoprofen in humans, following cyclodextrin complexation. Drug-cyclodextrin solid systems were prepared by kneading, co-evaporation, and freeze-drying. The formation of inclusion complexes with b-cyclodextrin and hydroxypropyl b-cyclodextrin in the solid state, were confirmed by differential scanning calorimetry, Fourier transform infrared spectroscopy, powder X-ray diffractometry, scanning electron microscopy studies, and comparative studies on the in vitro dissolution and in vivo absorption of ketoprofen in humans volunteers, were carried out. The initial dissolution rate of ketoprofen in the inclusion complexes was 15 fold higher, than that of plain drug powder. The maximal plasma concentration of ketoprofen after the oral administration of inclusion complexes to human volunteers increased about 1.5 fold (7.15 vs 4.65 mg/ml, and there was no significant increase in area under concentration-time curve, AUC0-5 (10.35 vs. 9.35 mg. hr/ml, compared to those of ketoprofen powder alone.

  1. Effect of nimesulide-a preferential COX-2 inhibitor on arterial blood pressure, compared to ketoprofen.

    Science.gov (United States)

    Saran, Tomasz; Sodolski, Wojciech; Sodolska, Katarzyna; Danilkiewicz, Wit Cezary; Schabowski, Janusz

    2004-01-01

    Clinical and experimental studies have shown that renal and cardiovascular effects of most selective COX-2 inhibitors (rofecoxib, celecoxib) are similar to other traditional NSAIDs (dual COX inhibitors). In these study the effect of nimesulide--preferential COX-2 inhibitor, administration on 24-hour blood pressure profile was investigated in 40 adult individuals on antihypertensive therapy with pain states caused by osteoartritis. Nimesulide was administered orally, twice a day at the conventional dose of 0.1 g for five days. In the next (or previous) 5 days the same patients were administered with ketoprofen at the dose of 0.05 g three times a day. On the last day of the NSAID administration period, 24-hour blood pressure monitoring was performed. Our results indicate no difference between nimesulide and ketoprofen effects on mean blood pressure values during antihypertensive therapy.

  2. A randomised trial comparing the efficacy and safety of topical ketoprofen in Transfersome(®) gel (IDEA-033) with oral ketoprofen and drug-free ultra-deformable Sequessome™ vesicles (TDT 064) for the treatment of muscle soreness following exercise.

    Science.gov (United States)

    Seidel, Egbert J; Rother, Matthias; Regenspurger, Katja; Rother, Ilka

    2016-01-01

    We compared the effectiveness of topical ketoprofen in Transfersome(®) gel (IDEA-033) with oral ketoprofen and drug-free Sequessome™ vesicles (FLEXISEQ(®) Sport; TDT 064) in reducing calf muscle soreness. One hundred and sixty eight healthy individuals with a pain score ≥ 3 (10-point scale) 12-16 h post-exercise (walking down stairs with an altitude of 300-400 m) were randomised to receive IDEA-033 plus oral placebo (two dose groups), oral ketoprofen plus TDT 064, or TDT 064 plus oral placebo. The primary endpoint was muscle soreness reduction from pre-dosing to Day 7. Higher pain scores were recorded with oral ketoprofen plus TDT 064 (mean ± s 462.4 ± 160.4) versus IDEA-033 plus oral placebo (434.7 ± 190.8; P = 0.2931) or TDT 064 plus oral placebo (376.2 ± 159.1; P = 0.0240) in the 7 days post-exercise. Recovery from muscle soreness was longer with oral ketoprofen plus TDT 064 (mean 91.0 ± 19.5 h) versus IDEA-033 plus placebo (mean 81.4 ± 22.9 h; P = 0.5964) or TDT 064 plus placebo (mean 78.9 ± 22.8 h; P = 0.0262). In conclusion, ultradeformable phospholipid vesicles ± ketoprofen did not retard recovery from muscle soreness. TDT 064 improves osteoarthritis-related pain and could be of interest as a treatment for joint pain during and post-exercise.

  3. Ketoprofen analysis in serum by capillary electrophoresis.

    Science.gov (United States)

    Friedberg, M; Shihabi, Z K

    1997-07-18

    A method for the quantification of ketoprofen, a new non-prescription non-steroidal anti-inflammatory drug, in serum, by capillary zone electrophoresis for therapeutic monitoring and emergency toxicology is described. Serum is deproteinized with acetonitrile in the presence of an internal standard, to remove serum proteins and to induce sample stacking. The migration time was about 10 min. The assay was linear between 1-10 mg/l without any interferences. The method compared well to an HPLC assay. The HPLC afforded a better detection limit, but the CE was less expensive to operate. This method demonstrates that capillary electrophoresis is a simple and effective method for determination of ketoprofen as well as other drugs in human serum at levels close to 1 mg/l.

  4. A 12-week randomized study of topical therapy with three dosages of ketoprofen in Transfersome® gel (IDEA-033 compared with the ketoprofen-free vehicle (TDT 064, in patients with osteoarthritis of the knee

    Directory of Open Access Journals (Sweden)

    Kneer W

    2013-10-01

    : 77.5%. Dermal reactions were the only relevant drug-related adverse events in all four groups. Conclusion: The 50 and 100 mg ketoprofen doses of IDEA-033 were only marginally superior to TDT 064 for reducing pain associated with knee OA. The study indicates a high treatment response to the topical ketoprofen-free vehicle TDT 064. Keyword: SequessomeTM, pain, non-steroidal anti-inflammatory drugs, drug-free, medical device

  5. Photobinding of ketoprofen in vitro and ex vivo

    NARCIS (Netherlands)

    Moser, J; Sarabia, Z; Minter, H; Lovell, WW; van Henegouwen, GMJB

    2000-01-01

    Ketoprofen (KP), a non-steroidal anti-inflammatory drug of the 2-aryl propionic class, has been shown to produce photoallergic side effects as well as cutaneous photosensitizing properties that induce other phototoxic effects. In the present study we investigated photobinding of ketoprofen to both h

  6. Value of diffusion weighted MR imaging as an early surrogate parameter for evaluation of tumor response to high-dose-rate brachytherapy of colorectal liver metastases

    Directory of Open Access Journals (Sweden)

    Röhl Friedrich-Wilhelm

    2011-04-01

    Full Text Available Abstract Background To assess the value of diffusion weighted imaging (DWI as an early surrogate parameter for treatment response of colorectal liver metastases to image-guided single-fraction 192Ir-high-dose-rate brachytherapy (HDR-BT. Methods Thirty patients with a total of 43 metastases underwent CT- or MRI-guided HDR-BT. In 13 of these patients a total of 15 additional lesions were identified, which were not treated at the initial session and served for comparison. Magnetic resonance imaging (MRI including breathhold echoplanar DWI sequences was performed prior to therapy (baseline MRI, 2 days after HDR-BT (early MRI as well as after 3 months (follow-up MRI. Tumor volume (TV and intratumoral apparent diffusion coefficient (ADC were measured independently by two radiologists. Statistical analysis was performed using univariate comparison, ANOVA and paired t test as well as Pearson's correlation. Results At early MRI no changes of TV and ADC were found for non-treated colorectal liver metastases. In contrast, mean TV of liver lesions treated with HDR-BT increased by 8.8% (p = 0.054 while mean tumor ADC decreased significantly by 11.4% (p p = 0.027 without significant change of mean ADC values. In contrast, mean TV of treated lesions decreased by 47.0% (p = 0.026 while the mean ADC increased inversely by 28.6% compared to baseline values (p Conclusions DWI is a promising imaging biomarker for early prediction of tumor response in patients with colorectal liver metastases treated with HDR-BT, yet the optimal interval between therapy and early follow-up needs to be elucidated.

  7. Influence of β-Cyclodextrin Complexation on Ketoprofen Release from Matrix Formulation

    OpenAIRE

    Shukla Vikesh; Masareddy Rajashree; Anghore Ashok; Manvi Fakkirappa.V.

    2009-01-01

    The main objective of this study was to improve the inclusion formation between Ketoprofen and β-cyclodextrin and thus enhance dissolution profile and bioavailability of the ketoprofen. Solubility studies demonstrated the formation of the ketoprofen-β-cyclodextrin inclusion complex with 1:1 stoichiometry. Equimolecular ketoprofen-β-cyclodextrin solid systems were prepared and characterized by DSC, FTIR and hot stage microscopy. Modification of the release of a ketoprofen from the hydrophilic ...

  8. KINETICS STUDY ON KETOPROFEN RELEASE FROM MINI TABLETS AND MULTI-COMPARTMENT SYSTEMS.

    Science.gov (United States)

    Stawarski, Tomasz; Sieradzki, Edmund; Gałecka, Emilia; Binek, Karolina

    2016-01-01

    Thanks to multi-compartment systems it is possible to modify drug release. Two types of mini tablets containing 12.5 mg of ketoprofen were made: mini tablets of immediate (IR) and sustained (SR) release. Some of the tablets of immediate release were coated with an enteric coating, thereby obtaining a delayed release effect (IRc). For each tablet type, release profiles were tested in three media: 0.1 M HCl, phosphate buffer pH 4.5 and phosphate buffer pH 6.8. Based on the obtained results, three appropriate multi-compartment models have been constructed and tested. The factor limiting the amount of available ketoprofen at the absorption place is pH of the environment. It was observed that the increase in pH caused the increase of ketoprofen solubility. Constructed multi-compartment systems allowed to change the composition and the dose of medicinal substances easily. Thanks to this it is possible to adjust the release profile of the active substance to the individual patient, which meets the expectations of personalized medicine.

  9. Enantioselective pharmacokinetics of ketoprofen in calves after intramuscular administration of a racemic mixture.

    Science.gov (United States)

    Plessers, E; Watteyn, A; Wyns, H; Pardon, B; De Baere, S; De Backer, P; Croubels, S

    2015-08-01

    The pharmacokinetic properties of ketoprofen were determined in 4-week-old calves after intramuscular (i.m.) injection of a racemic mixture at a dose of 3 mg/kg body weight. Due to possible enantioselective disposition kinetics and chiral inversion, the plasma concentrations of the R(-) and S(+) enantiomer were quantified separately, using a stereospecific HPLC-UV assay. A distinct predominance of the S(+) enantiomer was observed, as well as significantly different pharmacokinetic parameters between R(-) and S(+) ketoprofen. More in specific, a greater value for the mean area under the plasma concentration-time curve (AUC(0→∞)) (46.92 ± 7.75 and 11.13 ± 2.18 μg·h/mL for the S(+) and R(-) enantiomer, respectively), a lower apparent clearance (Cl/F) (32.8 ± 5.7 and 139.0 ± 25.1 mL/h·kg for the S(+) and R(-) enantiomer, respectively) and a lower apparent volume of distribution (V(d)/F) (139 ± 14.7 and 496 ± 139.4 mL/kg for the S(+) and R(-) enantiomer, respectively) were calculated for the S(+) enantiomer, indicating enantioselective pharmacokinetics for ketoprofen in calves following i.m. administration.

  10. Formulation and in vitro evaluation of ketoprofen fast-dissolving tablets.

    Science.gov (United States)

    Comoglu, Tansel; Inal, Ozge; Yaacoub, Hajar Ben

    2016-12-01

    Drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated as orally fast-disintegrating tablets (FDTs or ODTs). Therefore, taste masking of active ingredients becomes essential in these systems because the drug is entirely released in the mouth. Despite advances in the FDT technologies, formulation of drugs with a bitter taste is still a challenge, especially when the amount of drug is high. In this study, a new solution is being developed to incorporate higher doses of a model bitter taste drug; ketoprofen, without affecting the fast-disintegrating properties of the formulation. The unpleasant taste of the active drug usually masked by adding flavoring ingredients and sweeteners to improve taste and palatability but in this study a novel approach of using a polymer; Eudragit EPO and a granulation procedure of this polymer with the active drug was applied to mask the bitter taste of ketoprofen. In order to produce ketoprofen FDT formulations, a two-stepped procedure was followed; granulation process with the taste-masking agent (Eudragit EPO) and then direct compression (F3 and F4). In F1 and F2 formulations, granulation process was not implemented in order to observe the effect of application method of Eudragit EPO. As well as observing the effect of taste-masking agent, crospovidone and sodium starch glycolate were used in different concentrations (2, 4 and 8wt%) to examine the influence of superdisintegrants on FDT properties. All the FDTs containing 30 mg ketoprofen (F1, F2, F3 and F4) were evaluated by means of in vitro quality control tests.

  11. Postoperative Etoricoxib versus Ketoprofen Administration for Pain Management after Total Knee Arthroplasty: A Randomized, Double-Blind Controlled Study

    Directory of Open Access Journals (Sweden)

    Simona Cionac Florescu

    2015-01-01

    Full Text Available Objective. This randomized double-blind study compared the analgesic efficacy and tolerability of etoricoxib versus ketoprofen in 165 patients with elective total primary knee arthroplasty. Methods. After ethical committee approval, 165 patients were randomized in 3 groups: the etoricoxib group (E receiving etoricoxib 120 mg/day, at the end of surgery and in the first postoperative day; the ketoprofen group (K receiving ketoprofen 2 pills of 100 mg/day, the first at the end of surgery and then 1 pill every 12 hours in the surgery day and the first postoperative day; the placebo group (P. All groups received postoperatively the same analgesia protocol when NRS is over 3 with IV Perfalgan and morphine. The effectiveness was evaluated by the time from the initiation of spinal anesthesia until the first analgesic dose, the total amount of morphine administered in the surgery day and the first postoperative day, and the frequency of patients with side effects and necessary amount of adjuvant medication. Results. The baseline demographic characteristics were similar among the 3 groups. In both study days etoricoxib provided an analgesic effect superior to placebo and to ketoprofen, the total administered morphine being significantly lower in etoricoxib group. There were no statistically significant differences between groups regarding the side effects.

  12. Impact of the chemical and physical stability of ketoprofen compounded in various pharmaceutical bases on its topical and transdermal delivery.

    Science.gov (United States)

    Nornoo, Adwoa O; Wulz, Jordan; Yoon, Haena; Nan, Yu; Lese, Michele

    2016-03-01

    Increasing demands for individualized drug treatment has led to an increase in the practice of compounded medications. In this study, we determined the impact of the chemical and physical stability of ketoprofen (10%w/w) cream on its topical/transdermal delivery over a 6-month period. The shelf life of ketoprofen at 25 °C in the pharmaceutical bases LipoDerm and LipoBase (109.94 and 85.9 days) was significantly longer than that in Pluronic Lecithin Organogel (PLO; 44.81 days), justifying extending its beyond use date (BUD) from 30 (USP37/NF32) to at least 60 days in LipoDerm and LipoBase. All the creams evaluated exhibited shear-thinning flow behavior with moderate thixotropy, while the flow properties for LipoBase and PLO creams were altered at storage times greater than 90 days. The percentage of ketoprofen permeated through porcine ear skin was 13.7, 19.1 and 12.7% of the dose from LipoDerm, LipoBase and PLO, respectively and decreased 2- to 3-fold after 28 days of storage. Flux ranging from 85.3 to 446.7 µg/cm(2)/h and topical delivery, on the other hand, were not influenced by storage duration past 28 days. In conclusion, this study justifies extending the BUD of ketoprofen in LipoDerm and LipoBase to 60 days if used for topical delivery only.

  13. An oral controlled release matrix pellet formulation containing nanocrystalline ketoprofen.

    Science.gov (United States)

    Vergote, G J; Vervaet, C; Van Driessche, I; Hoste, S; De Smedt, S; Demeester, J; Jain, R A; Ruddy, S; Remon, J P

    2001-05-21

    A controlled release pellet formulation using a NanoCrystal colloidal dispersion of ketoprofen was developed. In order to be able to process the aqueous NanoCrystal colloidal dispersion into a hydrophobic solid dosage form a spray drying procedure was used. The in vitro dissolution profiles of wax based pellets loaded with nanocrystalline ketoprofen are compared with the profiles of wax based pellets loaded with microcrystalline ketoprofen and of a commercial sustained release ketoprofen formulation. Pellets were produced using a melt pelletisation technique. All pellet formulations were composed of a mixture of microcrystalline wax and starch derivatives. The starch derivatives used were waxy maltodextrin and drum dried corn starch. Varying the concentration of drum dried corn starch increased the release rate of ketoprofen but the ketoprofen recovery remained problematic. To increase the dissolution yield surfactants were utilised. The surfactants were either added during the production process of the NanoCrystal colloidal dispersion (sodium laurylsulphate) or during the pellet manufacturing process (Cremophor RH 40). Both methods resulted in a sustained but complete release of nanocrystalline ketoprofen from the matrix pellet formulations.

  14. Chemical analysis applied to the radiation sterilization of solid ketoprofen

    Science.gov (United States)

    Colak, S.; Maquille, A.; Tilquin, B.

    2006-01-01

    The aim of this work is to investigate the feasibility of radiation sterilization of ketoprofen from a chemical point of view. Although irradiated ketoprofen has already been studied in the literature [Katusin-Razem et al., Radiat. Phys. Chem. 73 111-116 (2005)], new results, on the basis of electron spin resonance (ESR) measurements and the use of hyphenated techniques (GC-MS and LC-MS), are obtained. The ESR spectra of irradiated ketoprofen consists of four unresolved resonance peaks and the mean G-value of ketoprofen is found to be 4 +/- 0.9 nmoles/J, which is very small. HPLC-UV analyses indicate that no significant loss of ketoprofen is detected after irradiation. LC-MS-MS analyses show that the structures of the non-volatile final products are similar to ketoprofen. Benzaldehyde is detected in the irradiated samples after dynamic-extraction GC-MS. The analyses show that ketoprofen is radioresistant and therefore might be radiosterilized.

  15. Efficacy of epicutaneous Diractin® (ketoprofen in Transfersome® gel for the treatment of pain related to eccentric muscle contractions

    Directory of Open Access Journals (Sweden)

    Matthias Rother

    2009-05-01

    Full Text Available Matthias Rother1,2, Egbert J Seidel3, Priscilla M Clarkson4, Stefan Mazgareanu1, Ulrich Vierl1, ilka Rother21IDEA AG, Muenchen, Germany; 2X-pert Med GmbH, Graefelfing, Germany; 3Department Physical and Rehabilitation Medicine, Sophien- and Hufeland-Clinic Centre, Weimar, Germany; 4Department of Kinesiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USAObjective: To investigate the effect of epicutaneously applied Diractin® (ketoprofen in Transfersome® gel on pain induced by eccentric muscle contractions. Methods: Three pilot studies which were subsequently pooled for a meta-analysis compared the efficacy of a single application of 25 mg ketoprofen in Diractin® to 25 mg oral ketoprofen and placebo for the treatment of pain induced by 50 eccentric contractions of the elbow flexor muscles. In addition, the effect of multiple usage of up to 100 mg ketoprofen in Diractin® bid over seven days on pain induced by walking down stairs with a total altitude of 200 meters was investigated.Results: A single dose of 25 mg ketoprofen in Diractin® after the elbow flexion exercise was significantly superior to placebo from 5 to 12 hours after treatment and also to oral ketoprofen at some time points after treatment. In contrast, oral ketoprofen was not different to placebo at any time after treatment. Multiple doses of up to 100 mg ketoprofen Diractin® provided significant more pain relief than placebo on muscle pain induced by walking down stairs. Conclusions: Eccentric exercise-induced muscle soreness was shown to be an appropriate acute pain model to evaluate the efficacy of nonsteroidal anti-inflammatory drugs applied epicutaneously with Transfersome® carriers. Diractin® proved to be efficacious in relieving pain from eccentric muscle contractions and muscle overexercise, respectively. The effect needs to be confirmed in a larger prospective clinical trial.Keywords: ketoprofen, Transfersome

  16. Efeitos da associação entre pequenas doses subaracnóideas de morfina e cetoprofeno venoso e oral em pacientes submetidas à cesariana Efectos de la asociación entre pequeñas dosis subaracnóideas de morfina y cetoprofeno venoso y oral en pacientes sometidas a cesariana Effects of low spinal morphine doses associated to intravenous and oral ketoprofen in patients submitted to cesarean sections

    Directory of Open Access Journals (Sweden)

    Eliana Marisa Ganem

    2003-08-01

    de efectos colaterales en pacientes sometidas a cesariana, bajo anestesia subaracnóidea con bupivacaína hiperbárica y morfina en las dosis de 0,05 mg y 0,1 mg, asociadas al cetoprofeno por las vías venosa y oral. MÉTODO: Participaron del estudio 60 gestantes de término, estado físico ASA I y II, que fueron sometidas a cesariana electiva. Las pacientes fueron divididas en dos grupos: grupo 1 - morfina 0,1 mg, grupo 2 - 0,05 mg, asociada a 15 mg de bupivacaína hiperbárica. Todas recibieron cetoprofeno (100 mg por vía venosa en el per-operatorio y por vía oral a cada 8 horas en el primer día del pos-operatorio. Las pacientes fueron evaluadas 6, 12 y 24 horas después del término de la cirugía, con relación a la intensidad del dolor y presencia de efectos colaterales (sedación, prurito, náusea y vómito. La presencia de estos últimos también fue evaluada en el per-operatorio. RESULTADOS: Ambos grupos fueron idénticos cuanto a los datos antropométricos y la duración de la cirugía y de la anestesia. También fueron homogéneos con relación a la intensidad del dolor pos-operatorio y a la presencia de prurito, sedación, náusea y vómito. CONCLUSIONES: La morfina, en las dosis de 0,05 mg y 0,1 mg administradas en el espacio subaracnóideo, asociada al cetoprofeno por las vías venosa y oral, presentó la misma calidad de analgesia pos-operatoria y determinó la misma ocurrencia de efectos colaterales.BACKGROUND AND OBJECTIVES: Low spinal morphine doses are effective in relieving postoperative pain of patients submitted to Cesarean sections, with low incidence of side-effects. This study aimed at evaluating postoperative analgesia and the incidence of side-effects in patients submitted to Cesarean sections under spinal anesthesia with hyperbaric bupivacaine and 0.05 mg and 0.1 mg morphine associated to intravenous and oral ketoprofen. METHODS: Sixty pregnant women, physical status ASA I and II, undergoing elective Cesarean sections, were divided in

  17. Formulation, optimization and evaluation of sustained release microsphere of ketoprofen

    Directory of Open Access Journals (Sweden)

    V Chirag Prajapati

    2012-01-01

    Full Text Available The objective of this study is to formulate ketoprofen loaded microspheres of Acrycoat S100 by an o/w emulsion solvent evaporation method. It potently inhibits the enzyme cyclooxygenase resulting in prostaglandin synthesis inhibition. Ketoprofen causes an irritation in the gastrointestinal mucous membrane and possesses a bitter taste and aftertaste. The half-life in plasma is about 1-2hrs. This makes ketoprofen a very good candidate for the formulation of controlled release dosage forms. Ketoprofen microspheres help to protect the gastric mucous membrane from drug irritation and to mask its taste. The prepared microspheres were evaluated for micromeritic properties, particle size, effect of surfactant concentration, percentage yield, incorporation efficiency, drug polymer compatibility (IR and DSC study, scanning electron microscopy and in vitro drug release. The microspheres produced exhibited good encapsulation efficiencies and micromeritic properties. Encapsulation efficiency of microsphere is around 78%. The mean diameters of microspheres were found in required micrometer range. The results of optimized formulations showed a narrow size distribution and smooth surface. The DSC and the FTIR analysis showed the absence of any potent incompatibility between the drug and the polymer. In-vitro release showed 86.4% drug release after 12 hours. Results of present study suggest that Acrycoat S100 loaded microsphere of ketoprofen can be successfully designed to develop sustained drug delivery system. The solvent evaporation method is a suitable technique for the preparation of Acrycoat S100 microspheres for controlling the release of Ketoprofen for a prolonged duration.

  18. Ketoprofen-poly(vinylpyrrolidone) physical interaction

    Science.gov (United States)

    Di Martino, Piera; Joiris, Etienne; Gobetto, Roberto; Masic, Admir; Palmieri, Giovanni F.; Martelli, Sante

    2004-04-01

    Amorphous solid solutions were obtained in different proportions by dissolving ketoprofen (Ket) and poly(vinylpyrrolidone) (PVP) K30 in methanol and by evaporating them under reduced pressure. Their physical properties were studied by powder X-ray diffraction and by differential scanning calorimetry and compared to that of same physical mixtures (PM). The interaction of Keto and poly(vinylpyrrolidone) K30 in the solid state was then investigated by 13C NMR CPMAS analysis. The results indicated that in the Ket-(PVP) co-precipitates, the ket molecules, interacting with their carboxylic group through hydrogen bonding with the poly(vinylpyrrolidone) moieties, are molecularly and irregularly dispersed within the amorphous solvendum that acts as mechanical substratum for amorphous stabilization. In their simple PM, no evidence exists of the Ket-polymer interaction during the considered time interval.

  19. Pharmacology of ketoprofen administered orally to pigs : an experimental and clinical study

    OpenAIRE

    2012-01-01

    Ketoprofen is a non-steroidal anti-inflammatory drug belonging to the 2-arylpropionic acid group. It has been widely used in domestic animals because of its anti-inflammatory, antipyretic and analgesic actions. Ketoprofen is a chiral compound existing in two enantiomeric forms, S (+) and R (-) ketoprofen. Each enantiomer has different pharmacodynamic and pharmacokinetic properties. The commercial products in veterinary medicine are 50:50 racemic mixtures of both enantiomers. Ketoprofen underg...

  20. Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

    OpenAIRE

    Mustonen Katja; Niemi Anneli; Raekallio Marja; Heinonen Mari; Peltoniemi Olli AT; Palviainen Mari; Siven Mia; Peltoniemi Marikki; Vainio Outi

    2012-01-01

    Abstract Background Ketoprofen is a non-steroidal anti-inflammatory drug which has been widely used for domestic animals. Orally administered racemic ketoprofen has been reported to be absorbed well in pigs, and bioavailability was almost complete. The objectives of this study were to analyze R- and S-ketoprofen concentrations in plasma after oral (PO) and intra muscular (IM) routes of administration, and to assess the relative bioavailability of racemic ketoprofen for both enantiomers betwee...

  1. Does ketoprofen or diclofenac pose the lowest risk to fish?

    Science.gov (United States)

    Cuklev, Filip; Fick, Jerker; Cvijovic, Marija; Kristiansson, Erik; Förlin, Lars; Larsson, D G Joakim

    2012-08-30

    Ketoprofen and diclofenac are non-steroidal anti-inflammatory drugs (NSAIDs) often used for similar indications, and both are frequently found in surface waters. Diclofenac affects organ histology and gene expression in fish at around 1 μg/L. Here, we exposed rainbow trout to ketoprofen (1, 10 and 100 μg/L) to investigate if this alternative causes less risk for pharmacological responses in fish. The bioconcentration factor from water to fish blood plasma was Ketoprofen only reached up to 0.6 ‰ of the human therapeutic plasma concentration, thus the probability of target-related effects was estimated to be fairly low. Accordingly, a comprehensive analysis of hepatic gene expression revealed no consistent responses. In some contrast, trout exposed to undiluted, treated sewage effluents bioconcentrated ketoprofen and other NSAIDs much more efficiently, according to a meta-analysis of recent studies. Neither of the setups is however an ideal representation of the field situation. If a controlled exposure system with a single chemical in pure water is a reasonable representation of the environment, then the use of ketoprofen is likely to pose a lower risk for wild fish than diclofenac, but if bioconcentration factors from effluent-exposed fish are applied, the risks may be more similar.

  2. Safety of Ketoprofen in Cow calves following repeated intravenous administration

    Directory of Open Access Journals (Sweden)

    R. D. Singh

    2009-06-01

    Full Text Available Ketoprofen is a non steroidal anti-inflammatory drug (NSAID used for its anti-inflammatory,analgesic and antipyretic properties in Veterinary Medicine. The present study was planned to assess safety of ketoprofen (3 mg.kg-1 after repeated intravenous administration at 24 hours interval for five days in six crossbred cow calves (6-12 months age and weighing between 60-122 kg. Ketoprofen in calves was found safe based on evaluation of haematological (Hb, PCV, TLC and DLC, blood biochemical (AKP, ACP, AST, ALT, LDH, Total bilirubin, Serum Creatinine, BUN, Serum total protein, Serum albumin and Blood glucose parameters. [Vet. World 2009; 2(3.000: 105-107

  3. Chiral extraction of ketoprofen enantiomers with chiral selector tartaric esters

    Institute of Scientific and Technical Information of China (English)

    ZHOU Dan; LIU Jia-jia; TANG Ke-wen; HUANG Ke-long

    2007-01-01

    Distribution behavior of ketoprofen enantiomers was examined in methanol aqueous and organic solvent mixture containing tartaric esters. The influence of length of alkyl chain of tartaric esters, concentration of L-tartaric esters and methanol aqueous, kind of organic solvent on partition ratio and separation factors was investigated. The results show that L-tartaric and D-tartaric esters have different chiral recognition abilities. S-ketoprofen is easily extracted by L-tartaric esters, and R-ketoprofen is easily extracted by D-tartaric esters. L-tartaric esters form more stable diastereomeric complexes with S-enantiomer than that with R-enantiomer. This distribution behavior is consistent with chiral recognition mechanism. With the increase of the concentration of tartaric ester from 0 to 0.3 mol/L, partition coefficient K and separation factor α increase. Also, the kind of organic solvent and the concentration of the methanol aqueous have significant influence on K and α.

  4. Comparison of gastrointestinal adverse effects of ketoprofen between adult and young cats.

    Science.gov (United States)

    Takata, Kenji; Hikasa, Yoshiaki; Satoh, Hiroshi

    2012-12-01

    This study elucidated differences in predisposition to the gastrointestinal adverse effects of ketoprofen between young and adult cats. Ketoprofen was administered subcutaneously (2.0 mg/kg, s.c.) once a day for 3 days. The animals were sacrificed 24 hr after final injection to allow examination of gastrointestinal mucosal lesions. Ketoprofen caused gastric lesions in adult cats (>6 months) but not in young cats (Ketoprofen caused more severe small intestinal lesions in adult cats than in young cats. In the study of prevention of lipopolysaccharide (LPS)-induced hyperthermia using ketoprofen, young and adult cats of both sexes were administered LPS (0.3 μg/kg, intravenously), and body temperature was measured 24 hr later. Ketoprofen was administered subcutaneously 30 min before LPS injection. LPS-induced hyperthermia was almost completely inhibited by pretreatment with ketoprofen in both adult and young cats. In the pharmacokinetics of ketoprofen, plasma concentrations were analyzed by high-performance liquid chromatography. No significant differences were observed in plasma concentrations of two mirror-image R(-) and S(+) ketoprofen between young and adult cats from 0.5-4 hr after injection. As observed in a previous study using flunixin, the degree of gastrointestinal damage was unrelated to plasma concentrations of ketoprofen. The results of this study demonstrated that ketoprofen is safer for use in young cats than in adult cats from the viewpoint of gastrointestinal adverse effects.

  5. Presurgical ketoprofen, but not morphine, dipyrone, diclofenac or tenoxicam, preempts post-incisional mechanical allodynia in rats

    Directory of Open Access Journals (Sweden)

    Prado W.A.

    2002-01-01

    Full Text Available The treatment of pain before it initiates may prevent the persistent pain-induced changes in the central nervous system that amplify pain long after the initial stimulus. The effects of pre- or postoperative intraperitoneal administration of morphine (2 to 8 mg/kg, dipyrone (40 and 80 mg/kg, diclofenac (2 to 8 mg/kg, ketoprofen (10 and 20 mg/kg, and tenoxicam (10 and 20 mg/kg were studied in a rat model of post-incisional pain. Groups of 5 to 8 male Wistar rats (140-160 g were used to test each drug dose. An incision was made on the plantar surface of a hind paw and the changes in the withdrawal threshold to mechanical stimulation were evaluated with Von Frey filaments at 1, 2, 6 and 24 h after the surgery. Tenoxicam was given 12 or 6 h preoperatively, whereas the remaining drugs were given 2 h or 30 min preoperatively. Postoperative drugs were all given 5 min after surgery. No drug abolished allodynia when injected before or after surgery, but thresholds were significantly higher than in control during up to 2 h following ketoprofen, 6 h following diclofenac, and 24 h following morphine, dipyrone or tenoxicam when drugs were injected postoperatively. Significant differences between pre- and postoperative treatments were obtained only with ketoprofen administered 30 min before surgery. Preoperative (2 h intraplantar, but not intrathecal, ketoprofen reduced the post-incisional pain for up to 24 h after surgery. It is concluded that stimuli generated in the inflamed tissue, rather than changes in the central nervous system are relevant for the persistence of pain in the model of post-incisional pain.

  6. A dose-response study of topical allyl-isothiocyanate (mustard oil) as human surrogate model of pain, hyperalgesia, and neurogenic inflammation

    DEFF Research Database (Denmark)

    Andersen, Hjalte Holm; Lo Vecchio, Silvia; Gazerani, Parisa

    2017-01-01

    , sensitizing irritant remains to be elucidated in human skin. Three concentrations of AITC (10%, 50%, 90%) and vehicle (paraffin) were applied for 5 min to 3x3 cm areas on the volar forearms in 14 healthy volunteers, and evoked pain intensity (visual analog scale 0-100 mm) and pain quality were assessed...... AITC exposure. AITC induced significant dose-dependent, moderate-to-severe spontaneous burning pain, mechanical and heat hyperalgesia as well as dynamic mechanical allodynia (p

  7. [A randomized, double blind comparison of pethidine and ketoprofen as adjuvants for lignocaine in intravenous regional anaesthesia].

    Science.gov (United States)

    Desai, Sameer N; Santhosh, M C B

    2014-01-01

    A review of all the adjuncts for intravenous regional anaesthesia concluded that there is good evidence to recommend NonSteroidal Anti-Inflammatory agents and pethidine in the dose of 30mg dose as adjuncts to intravenous regional anaesthesia. But there are no studies to compare pethidine of 30mg dose to any of the NonSteroidal Anti-Inflammatory agents. In a prospective, randomized, double blind study, 45 patients were given intravenous regional anaesthesia with either lignocaine alone or lignocaine with pethidine 30mg or lignocaine with ketprofen 100mg. Fentanyl was used as rescue analgesic during surgery. For the first 6h of postoperative period analgesia was provided by fentanyl injection and between 6 and 24h analgesia was provided by diclofenac tablets. Visual analogue scores for pain and consumption of fentanyl and diclofenac were compared. The block was inadequate for one case each in lignocaine group and pethidine group, so general anaesthesia was provided. Time for the first dose of fentanyl required for postoperative analgesia was significantly more in pethidine and ketoprofen groups compared to lignocaine group (156.7±148.8 and 153.0±106.0 vs. 52.1±52.4min respectively). Total fentanyl consumption in first 6 h of postoperative period was less in pethidine and ketoprofen groups compared to lignocaine group (37.5±29.0 mcg, 38.3±20.8mcg vs. 64.2±27.2mcg respectively). Consumption of diclofenac tablets was 2.4±0.7, 2.5±0.5 and 2.0±0.7 in the control, pethidine and ketoprofen group respectively, which was statistically not significant. Side effects were not significantly different between the groups. Both pethidine and ketoprofen are equally effective in providing postoperative analgesia up to 6h, without significant difference in the side effects and none of the adjuncts provide significant analgesia after 6h. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  8. A randomized, double blind comparison of pethidine and ketoprofen as adjuvants for lignocaine in intravenous regional anaesthesia

    Directory of Open Access Journals (Sweden)

    Sameer N. Desai

    2014-07-01

    Full Text Available BACKGROUND AND OBJECTIVES: A review of all the adjuncts for intravenous regional anaesthesia concluded that there is good evidence to recommend NonSteroidal Anti-Inflammatory agents and pethidine in the dose of 30 mg dose as adjuncts to intravenous regional anaesthesia. But there are no studies to compare pethidine of 30 mg dose to any of the NonSteroidal Anti-Inflammatory agents. METHODS: In a prospective, randomized, double blind study, 45 patients were given intravenous regional anaesthesia with either lignocaine alone or lignocaine with pethidine 30 mg or lignocaine with ketprofen 100 mg. Fentanyl was used as rescue analgesic during surgery. For the first 6 h of postoperative period analgesia was provided by fentanyl injection and between 6 and 24 h analgesia was provided by diclofenac tablets. Visual analogue scores for pain and consumption of fentanyl and diclofenac were compared. RESULTS: The block was inadequate for one case each in lignocaine group and pethidine group, so general anaesthesia was provided. Time for the first dose of fentanyl required for postoperative analgesia was significantly more in pethidine and ketoprofen groups compared to lignocaine group (156.7 ± 148.8 and 153.0 ± 106.0 vs. 52.1 ± 52.4 min respectively. Total fentanyl consumption in first 6 h of postoperative period was less in pethidine and ketoprofen groups compared to lignocaine group (37.5 ± 29.0 mcg, 38.3 ± 20.8 mcg vs. 64.2 ± 27.2 mcg respectively. Consumption of diclofenac tablets was 2.4 ± 0.7, 2.5 ± 0.5 and 2.0 ± 0.7 in the control, pethidine and ketoprofen group respectively, which was statistically not significant. Side effects were not significantly different between the groups. CONCLUSION: Both pethidine and ketoprofen are equally effective in providing postoperative analgesia up to 6 h, without significant difference in the side effects and none of the adjuncts provide significant analgesia after 6 h.

  9. A randomized, double blind comparison of pethidine and ketoprofen as adjuvants for lignocaine in intravenous regional anaesthesia.

    Science.gov (United States)

    Desai, Sameer N; Santhosh, M C B

    2014-01-01

    A review of all the adjuncts for intravenous regional anaesthesia concluded that there is good evidence to recommend NonSteroidal Anti-Inflammatory agents and pethidine in the dose of 30mg dose as adjuncts to intravenous regional anaesthesia. But there are no studies to compare pethidine of 30mg dose to any of the NonSteroidal Anti-Inflammatory agents. In a prospective, randomized, double blind study, 45 patients were given intravenous regional anaesthesia with either lignocaine alone or lignocaine with pethidine 30mg or lignocaine with ketprofen 100mg. Fentanyl was used as rescue analgesic during surgery. For the first 6h of postoperative period analgesia was provided by fentanyl injection and between 6 and 24h analgesia was provided by diclofenac tablets. Visual analogue scores for pain and consumption of fentanyl and diclofenac were compared. The block was inadequate for one case each in lignocaine group and pethidine group, so general anaesthesia was provided. Time for the first dose of fentanyl required for postoperative analgesia was significantly more in pethidine and ketoprofen groups compared to lignocaine group (156.7±148.8 and 153.0±106.0 vs. 52.1±52.4min respectively). Total fentanyl consumption in first 6h of postoperative period was less in pethidine and ketoprofen groups compared to lignocaine group (37.5±29.0mcg, 38.3±20.8mcg vs. 64.2±27.2mcg respectively). Consumption of diclofenac tablets was 2.4±0.7, 2.5±0.5 and 2.0±0.7 in the control, pethidine and ketoprofen group respectively, which was statistically not significant. Side effects were not significantly different between the groups. Both pethidine and ketoprofen are equally effective in providing postoperative analgesia up to 6h, without significant difference in the side effects and none of the adjuncts provide significant analgesia after 6h. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  10. Risk evaluation of the Arctic environmental POP exposure based on critical body residue and critical daily dose using captive Greenland sledge dogs (Canis familiaris) as surrogate species.

    Science.gov (United States)

    Sonne, Christian; Gustavson, Kim; Eulaers, Igor; Desforges, Jean-Pierre; Letcher, Robert J; Rigét, Frank F; Styrishave, Bjarne; Dietz, Rune

    2016-03-01

    The risk from POP (persistent organic pollutant) exposure and subsequent reproductive, immunotoxic and liver histopathological effects was evaluated in a classical parallel trial on Greenland sledge dogs (Canis familiaris) fed contaminated minke whale (Balaenoptera acutorostrata) blubber. First the critical body residues (CBRs) were estimated using the physiologically-based pharmacokinetic (PBPK) model for seven POP compounds based on rat critical daily doses (CDDs). These were then compared with the actual daily oral POP doses (DD) and body residues (BR) in the sledge dogs by calculating risk quotients (RQDD: DD/CDD; RQBR: BR/CBR; ≥1 indicates risk). The results showed that risk quotients for reproductive, immunotoxic and liver histopathological effects were significantly lowest in the control group (pPOP exposure negatively impacts steroid hormones, various immune parameters, as well as liver histopathology in sledge dogs. It is also clear that RQBR is the best reflector of health effects from POP exposure and that it is especially accurate in predicting immune and reproductive effects. We recommend that PBPK modelled (CBR) and RQBR should be used in the assessment of POP exposure and health effects in Arctic top predators. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Nanosized ethosomes bearing ketoprofen for improved transdermal delivery

    OpenAIRE

    2011-01-01

    The potential of ethosomes for delivering ketoprofen via skin was evaluated. The ethosomes were prepared, optimized and characterized. Vesicular shape, size and entrapment efficiency were determined by transmission electron microscopy, dynamic light scattering and minicolumn centrifugation technique, respectively. Vesicle sizes varied from 120.3±6.1 to 410.2±21.8 nm depending on the concentrations of soya phosphatidyl choline (SPC) and ethanol. Entrapment efficiency increased with concentrati...

  12. Nanoemulsion Based Hydrogel for Enhanced Transdermal Delivery of Ketoprofen

    OpenAIRE

    2014-01-01

    The aim of the present study was to investigate the nanoemulgel as transdermal delivery system for poorly water soluble drug, ketoprofen, in order to overcome the troubles associated with its oral delivery. Different nanoemulsion components (oil, surfactant, and cosurfactant) were selected on the basis of solubility and emulsification ability. Pseudoternary phase diagrams were constructed using titration method to figure out the concentration range of components. Carbomer 940 was added as gel...

  13. Nanoemulsion Based Hydrogel for Enhanced Transdermal Delivery of Ketoprofen

    Directory of Open Access Journals (Sweden)

    Ritika Arora

    2014-01-01

    Full Text Available The aim of the present study was to investigate the nanoemulgel as transdermal delivery system for poorly water soluble drug, ketoprofen, in order to overcome the troubles associated with its oral delivery. Different nanoemulsion components (oil, surfactant, and cosurfactant were selected on the basis of solubility and emulsification ability. Pseudoternary phase diagrams were constructed using titration method to figure out the concentration range of components. Carbomer 940 was added as gel matrix to convert nanoemulsion into nanoemulgel. Drug loaded nanoemulsions and nanoemulgels were characterized for particle size, TEM, viscosity, conductivity, spreadability, rheological behavior, and permeation studies using Wistar rat skin and stability studies. Transdermal permeation of ketoprofen from nanoemulgels was determined by using Franz diffusion cell. Nanoemulgel containing 6% oleic acid as oil, 35% Tween 80, and Transcutol P as surfactant cosurfactant mixture, 56.5% water, 2.5% drug, and 0.6% carbomer was concluded as optimized formulation (NG6. The ex vivo permeation profile of optimized formulation was compared with nanoemulsion and marketed formulation (Fastum. Nanoemulgel showed significantly higher (P<0.05 cumulative amount of drug permeated and flux along with lower lag time and skin retention than marketed formulation. Thus, the study substantiated that nanoemulgel formulation can be used as a feasible alternative to conventional formulations of ketoprofen with advanced permeation characteristics for transdermal application.

  14. Birds as biodiversity surrogates

    DEFF Research Database (Denmark)

    Larsen, Frank Wugt; Bladt, Jesper Stentoft; Balmford, Andrew

    2012-01-01

    1. Most biodiversity is still unknown, and therefore, priority areas for conservation typically are identified based on the presence of surrogates, or indicator groups. Birds are commonly used as surrogates of biodiversity owing to the wide availability of relevant data and their broad popular...... appeal. However, some studies have found birds to perform relatively poorly as indicators. We therefore ask how the effectiveness of this approach can be improved by supplementing data on birds with information on other taxa. 2. Here, we explore two strategies using (i) species data for other taxa...... areas identified on the basis of birds alone performed well in representing overall species diversity where birds were relatively speciose compared to the other taxa in the data sets. Adding species data for one taxon increased surrogate effectiveness better than adding genus- and family-level data...

  15. Plutonium radiation surrogate

    Science.gov (United States)

    Frank, Michael I [Dublin, CA

    2010-02-02

    A self-contained source of gamma-ray and neutron radiation suitable for use as a radiation surrogate for weapons-grade plutonium is described. The source generates a radiation spectrum similar to that of weapons-grade plutonium at 5% energy resolution between 59 and 2614 keV, but contains no special nuclear material and emits little .alpha.-particle radiation. The weapons-grade plutonium radiation surrogate also emits neutrons having fluxes commensurate with the gamma-radiation intensities employed.

  16. Penetapan Harga PKA Dari Ketoprofen Bpfi Dan Beberapa Sediaan Tablet Ketoprofen Yang Terdapat Dipasaran Dengan Metode Spektrofotometri Ultraviolet Secara Isobestik

    OpenAIRE

    Rina Astuti

    2010-01-01

    Ketoprofen yang terdapat dipasaran diproduksi oleh beberapa industri farmasi dan masing-masing industri memiliki formulasi yang berbeda, dengan perbedaan formulasi ini tentu akan mempengaruhi harga pKa dari molekul obat yang akan menentukan absorpsi dan distribusi obat dalam jaringan-jaringan tubuh. Harga pKa yang diperoleh dari suatu senyawa tergantung dari metode yang digunakan, diantaranya perhitungan secara ? Hammett (Siswandono & Soekardjo, 1998), secara Spektrofotometri Ultraviolet m...

  17. Stability of ketoprofen-dextran ester prodrugs in homogenates of various segments of pig GI tract

    DEFF Research Database (Denmark)

    Larsen, C.; Jensen, Bodil Hamborg; Olesen, H. P.

    1991-01-01

    Initial velocities of ketoprofen formation from ketoprofen-dextran ester prodrugs incubated in homogenates of various segments of the pig GI-tract were determined. Enzyme-mediated drug release was found in caecum and colon homogenates with their contents, whereas release rates in the stomach...

  18. Effect of ketoprofen on pre-weaning piglet mortality on commercial farms.

    Science.gov (United States)

    Homedes, Josep; Salichs, Marta; Sabaté, David; Sust, Mariano; Fabre, Ramon

    2014-09-01

    The effect of ketoprofen on pre-weaning piglet mortality was evaluated in a large-scale study on commercial farms. Sows (n= 1486) from 15 farms were included. Half of the sows received 3 mg/kg ketoprofen in a single intramuscular administration within 12 h after farrowing. The other half remained untreated. Pre-weaning mortality was lower in the ketoprofen-treated group than in the control group (8.43% vs. 10.24%, respectively; P= 0.010). The major impact of ketoprofen on mortality was seen between days 2 and 7 postpartum (mortality rates of 2.75% vs. 4.02% for treated and control groups, respectively; P= 0.001). In addition, ketoprofen treatment was associated with a higher number of piglets weaned per litter than when no treatment was given (10.0 vs. 9.84, respectively; P= 0.012).

  19. IN VITRO IRREVERSIBLE BINDING AND DEGRADATION OF (R- AND (S-KETOPROFEN GLUCURONIDES TO PLASMA PROTEINS

    Directory of Open Access Journals (Sweden)

    PETER J. HAYBALL

    2007-01-01

    Full Text Available This study describes the in vitro degradation studies of the diastereomeric ketoprofen glucuronides, under physiological conditions (pH 7.4, 37°C, (R-ketoprofen glucuronide t½ = 30 min, (S-ketoprofen glucuronide t½ = 70 min and the irreversible binding of diastereomeric ketoprofen glucuronides (15 μg/ml to human serum albumin (HSA (289 μM and human plasma under physiological conditions (pH 7.4, 37ºC. The (R-ketoprofen glucuronide irreversibly bound to a greater extent in both human plasma and human serum albumin. This is the reverse to that found in previous studies. These findings further support the hypothesis that faster degradation of 1-O-acyl glucuronide (in this case the (R-diastereomer is associated with a greater extent of irreversible binding.

  20. Evaluation of the brain, renal, and hepatic effects of flunixin meglumine, ketoprofen, and phenylbutazone administration in Iranian fat-tailed sheep.

    Science.gov (United States)

    Mozaffari, Ali Asghar; Derakhshanfar, Amin

    2011-10-01

    The purpose of this study was to evaluate the brain, renal, and hepatic effects of three NSAIDs (flunixin meglumine, ketoprofen, and phenylbutazone) when administered IV to clinically normal Iranian fat-tailed sheep. The experiments were conducted on twenty clinically normal adult female sheep. Sheep were randomly assigned to four groups: saline (n = 5), flunixin meglumine (n = 5), ketoprofen (n = 5), and phenylbutazone (n = 5). Drug administration was initiated at 8 AM: on day 1 and continued every 12 h for 12 days. Flunixin meglumine, ketoprofen, and phenylbutazone were administered at dose rate of 2.2, 4, and 4 mg/kg, respectively. Daily blood and urine samples were collected from all sheep for hematologic, enzymes activity, and urinalysis. Immediately after euthanasia, complete necropsy was performed on all sheep and gross lesions were recorded. Clinical, hematological, serum, and urine analysis and histopatholgical findings were described. When the use of these compounds is contemplated in clinical cases, the risk of adverse effects and the comparative toxic potential should be considered, along with the efficacy of the compound for the condition being treated.

  1. Differential mortality of male spectacled eiders (Somateria fischeri) and king eiders (Somateria spectabilis) subsequent to anesthesia with propofol, bupivacaine, and ketoprofen

    Science.gov (United States)

    Mulcahy, Daniel M.; Tuomi, Pamela A.; Larsen, R.S.

    2003-01-01

    Twenty free-ranging spectacled eiders (Somateria fischeri; 10 male, 10 female), 11 free-ranging king eiders (Somateria spectabilis; 6 male, 5 female), and 20 female common eiders (Somateria mollissima) were anesthetized with propofol, bupivacaine, and ketoprofen for the surgical implantation of satellite transmitters. Propofol was given to induce and maintain anesthesia (mean total dose, 26.2-45.6 mg/kg IV), bupivacaine (2-10 mg/kg SC) was infused into the incision site for local analgesia, and ketoprofen (2-5 mg/kg IM) was given at the time of surgery for postoperative analgesia. Four of 10 male spectacled eiders and 5 of 6 male king eiders died within 1-4 days after surgery. None of the female spectacled or common eiders and only 1 of the 5 female king eiders died during the same postoperative period. Histopathologic findings in 2 dead male king eiders were severe renal tubular necrosis, acute rhabdomyolysis, and mild visceral gout. Necropsy findings in 3 other dead male king eiders were consistent with visceral gout. We suspect that the perioperative use of ketoprofen caused lethal renal damage in the male eiders. Male eiders may be more susceptible to renal damage than females because of behavioral differences during their short stay on land in mating season. The combination of propofol, bupivacaine, and ketoprofen should not be used to anesthetize free-ranging male eiders, and nonsteroidal anti-inflammatory drugs should not be used perioperatively in any bird that may be predisposed to renal insufficiency.

  2. Developments in Surrogating Methods

    Directory of Open Access Journals (Sweden)

    Hans van Dormolen

    2005-11-01

    Full Text Available In this paper, I would like to talk about the developments in surrogating methods for preservation. My main focus will be on the technical aspects of preservation surrogates. This means that I will tell you something about my job as Quality Manager Microfilming for the Netherlands’ national preservation program, Metamorfoze, which is coordinated by the National Library. I am responsible for the quality of the preservation microfilms, which are produced for Metamorfoze. Firstly, I will elaborate on developments in preservation methods in relation to the following subjects: · Preservation microfilms · Scanning of preservation microfilms · Preservation scanning · Computer Output Microfilm. In the closing paragraphs of this paper, I would like to tell you something about the methylene blue test. This is an important test for long-term storage of preservation microfilms. Also, I will give you a brief report on the Cellulose Acetate Microfilm Conference that was held in the British Library in London, May 2005.

  3. Effect of microneedle on the pharmacokinetics of ketoprofen from its transdermal formulations.

    Science.gov (United States)

    So, Jae-Woo; Park, Hyoun-Hyang; Lee, Seung S; Kim, Dong-Chool; Shin, Sang-Chul; Cho, Cheong-Weon

    2009-01-01

    Non-invasive transdermal delivery using microneedle arrays was recently introduced to deliver a variety of large and hydrophilic compounds into the skin, including proteins and DNA. In this study, a microneedle array was applied to the delivery of a hydrophobic drug, ketoprofen, to determine if transdermal delivery in rats can be improved without the need for permeation enhancers. The ability of a microneedle to increase the skin permeability of ketoprofen was tested using the following procedure. A microneedle array was inserted into the lower back skin of a rat using a clip for 10 min. Subsequently, 24 mg/kg of a ketoprofen gel was loaded on the same site where the microneedle had been applied. Simultaneously, the microneedle was coated with 24 mg/kg of a ketoprofen gel, and inserted into the skin using a clip for 10 min. As a negative control experiment, only 24 mg/kg of the ketoprofen gel was applied to the shaved lower back of a rat. Blood samples were taken at the indicated times. The plasma concentration (C(p)) was obtained as a function of time (t), and the pharmacokinetic parameters were calculated using the BE program. The group loaded with the microneedle coated with ketoprofen gel showed a 1.86-fold and 2.86-fold increase in the AUC and C((max)) compared with the ketoprofen gel alone group. These results suggest that a microneedle can be an ideal tool for transdermal delivery products.

  4. Composite materials for medical purposes based on polyvinylpyrrolidone modified with ketoprofen and silver nanoparticles

    Science.gov (United States)

    Nikitin, L. N.; Vasil'Kov, A. Yu.; Banchero, M.; Manna, L.; Naumkin, A. V.; Podshibikhin, V. L.; Abramchuk, S. S.; Buzin, M. I.; Korlyukov, A. A.; Khokhlov, A. R.

    2011-07-01

    A method for obtaining composite medical materials based on polyvinylpyrrolidone (PVP K15) modified with ketoprofen in a medium of supercritical carbon dioxide and with Ag nanoparticles prepared by metal vapor synthesis is developed. A system in which ketoprofen and Ag nanoparticles with an average size of ˜16 nm are uniformly distributed over the bulk of PVP is obtained. It is found that the yield of ketoprofen from the composite in the physiological solution is higher than that for an analogous system obtained by mechanical mixing of the components.

  5. Place of topical therapy in rheumatology. Ketoprofen gel is a focus

    Directory of Open Access Journals (Sweden)

    V G Barskova

    2008-09-01

    Full Text Available According to the data of recent studies, the topical formulations of nonsteroidal anti-inflammatory drugs (NSAIDs used in rheumatic diseases are of the greatest importance in the treatment of osteoarthrosis. Comparative studies have demonstrated that ketoprofen-containing gel has some advantage over other NSAIDs. Topical formulations based on ketoprofen (Fastum® gel are effective, fast-acting, and able to aid patients in relieving pain and improving the quality of life.

  6. Formulasi Niosom Ketoprofen Dan Prediksi Penggunaan Transdermal Secara In Vivo Pada Kelinci

    OpenAIRE

    Ismail, Isriani; Wahyudin, Elly; Rahman, Latifah

    2013-01-01

    Niosom adalah system vesikel yang dapat digunakan sebagai pembawa obat lipofilik, hidrofilik dan ampifilik. Ketoprofen adalah salah satu golongan AINS yang sangat sukar larut dalam air dan dalam pH cairan lambung, paparan lama pada mukosa lambung dapat memperparah ulcus, sehingga bahan obat patut dikembangkan dalam bentuk sediaan lain dengan rute yang lebih nyaman, misalnya dalma bentuk sedian transdermal. Penelitian ini bertujuan untuk memformulasi niosom yang dapat menjerap ketoprofen secar...

  7. Biowaiver monographs for immediate-release solid oral dosage forms: ketoprofen.

    Science.gov (United States)

    Shohin, Igor E; Kulinich, Julia I; Ramenskaya, Galina V; Abrahamsson, Bertil; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Groot, D W; Barends, Dirk M; Dressman, Jennifer B

    2012-10-01

    Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing ketoprofen are reviewed. Ketoprofen's solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability (BA)/dissolution data were taken into consideration. The available data suggest that according to the current Biopharmaceutics Classification System (BCS) and all current guidances, ketoprofen is a weak acid that would be assigned to BCS Class II. The extent of ketoprofen absorption seems not to depend on formulation or excipients, so the risk of bioinequivalence in terms of area under the curve is very low, but the rate of absorption (i.e., BE in terms of peak plasma concentration, C(max) ) can be altered by formulation. Current in vitro dissolution methods may not always reflect differences in terms of C(max) for BCS Class II weak acids; however, such differences in absorption rate are acceptable for ketoprofen with respect to patient risks. As ketoprofen products may be taken before or after meals, the rate of absorption cannot be considered crucial to drug action. Therefore, a biowaiver for IR ketoprofen solid oral dosage form is considered feasible, provided that (a) the test product contains only excipients present also in IR solid oral drug products containing ketoprofen, which are approved in International Conference on Harmonisation or associated countries, for instance, as presented in this paper; (b) both the test drug product and the comparator dissolve 85% in 30 min or less in pH 6.8 buffer; and (c) test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. When one or more of these conditions are not fulfilled, BE should be established in vivo.

  8. Flow injection analysis of ketoprofen based on the order transform second chemiluminescence reaction

    Science.gov (United States)

    Zhuang, Yafeng; Cao, Guiping; Ge, Chuanqin

    2012-01-01

    This paper explores an order-transform-second-chemiluminescence (OTSCL) method combining the flow injection technique for the determination of ketoprofen. When ketoprofen solution was injected into the mixture after the end of the reaction of alkaline luminol and sodium periodate or sodium periodate solution was injected into the reaction mixture of ketoprofen and alkaline luminol, a new chemiluminescence (CL) reaction was initiated and strong CL signal was detected. A mechanism for the OTSCL has been proposed on the basis of the chemiluminescence kinetic characteristic, UV-visible absorption and chemiluminescent spectra. Under optimal experimental conditions, the CL response is proportional to the concentration of ketoprofen over the range of 2.0 × 10 -7 to 1.0 × 10 -5 mol/L with a correlation coefficient of 0.9950 and a detection limit of 8.0 × 10 -9 mol/L (3 σ). The relative standard deviation for 11 repetitive determinations of 1.0 × 10 -6 mol/L ketoprofen is 2.9%. The utility of this method was demonstrated by determining ketoprofen in pharmaceutical formulations without interference from its potential impurities.

  9. Effects of ketoprofen for prevention of postoperative cognitive dysfunction in aged rats.

    Science.gov (United States)

    Kawano, Takashi; Takahashi, Tetsuya; Iwata, Hideki; Morikawa, Akihiro; Imori, Satoko; Waki, Sayaka; Tamura, Takahiko; Yamazaki, Fumimoto; Eguchi, Satoru; Kumagai, Naoko; Yokoyama, Masataka

    2014-12-01

    Postoperative cognitive dysfunction is a common geriatric complication that may be associated with increased mortality. Here, we investigated the effects of postoperative analgesia with ketoprofen on cognitive functions in aged animals and compared its effectiveness to morphine. Rats were randomly allocated to one of four groups: isoflurane anesthesia without surgery (group C), isoflurane anesthesia with laparotomy (group IL), and isoflurane anesthesia with laparotomy plus postoperative analgesia with ketoprofen or morphine. There was no difference in postoperative locomotor activity among groups. In group IL, postoperative pain levels assessed by the Rat Grimace Scale significantly increased until 8 h after surgery, which was similarly inhibited by both ketoprofen and morphine. Cognitive function was assessed using radial arm maze testing for 12 consecutive days from postoperative day 3. Results showed that the number of memory errors in group IL were significantly higher than those in goup C. However, both ketoprofen and morphine could attenuate the increase in memory errors following surgery to a similar degree. Conversely, ketoprofen showed no effect on cognitive function in the nonsurgical rats that did not experience pain. Our findings suggest that postoperative analgesia with ketoprofen can prevent the development of surgery-associated memory deficits via its pain-relieving effects.

  10. Stabilization of Human Serum Albumin against Urea Denaturation by Diazepam and Ketoprofen.

    Science.gov (United States)

    Manoharan, Pralad; Wong, Yin H; Tayyab, Saad

    2015-01-01

    Stabilizing effect of diazepam and ketoprofen, Sudlow's site II markers on human serum albumin (HSA) against urea denaturation was studied using fluorescence spectroscopy. The two-step, three-state urea transition of HSA was transformed into a single-step, two-state transition with the abolishment of the intermediate state along with a shift of the transition curve towards higher urea concentrations in the presence of diazepam or ketoprofen. Interestingly, a greater shift in the transition curve of HSA was observed in the presence of ketoprofen compared to diazepam. A comparison of the intrinsic fluorescence and three-dimensional fluorescence spectra of HSA and partially-denatured HSAs, obtained in the absence and the presence of diazepam or ketoprofen suggested significant retention of native-like conformation in the partially-denatured states of HSA in the presence of Sudlow's site II markers. Taken together, all these results suggested stabilization of HSA in the presence of diazepam or ketoprofen, being greater in the presence of ketoprofen.

  11. Encapsulated Ketoprofen by Chitosan-Alginat based on Type and Variation of Tween 80 and Span 80 Concentration.

    OpenAIRE

    Tuti Wukirsari; Mersi Kurniati; Napthaleni; Purwantiningsih Sugita

    2010-01-01

    Encapsulated Ketoprofen by Chitosan-Alginat based on Type and Variation of Tween 80 and Span 80Concentration. Ketoprofen has been encapsulated by chitosan-alginate based on types of surfactant and it’sconcentration. The variations of concentration either Tween 80 (polietilena sorbitanmonooleat) or Span 80(sorbitanmonooleat) that used were around (1- 3)% concentrations with stirring around (15-60) minutes. The using ofTween 80 resulted efficiency of encapsulated ketoprofen and nano particle si...

  12. Surrogate Modeling for Geometry Optimization

    DEFF Research Database (Denmark)

    Rojas Larrazabal, Marielba de la Caridad; Abraham, Yonas; Holzwarth, Natalie;

    2009-01-01

    A new approach for optimizing the nuclear geometry of an atomic system is described. Instead of the original expensive objective function (energy functional), a small number of simpler surrogates is used.......A new approach for optimizing the nuclear geometry of an atomic system is described. Instead of the original expensive objective function (energy functional), a small number of simpler surrogates is used....

  13. Surrogate Endpoints in Suicide Research

    Science.gov (United States)

    Wortzel, Hal S.; Gutierrez, Peter M.; Homaifar, Beeta Y.; Breshears, Ryan E.; Harwood, Jeri E.

    2010-01-01

    Surrogate endpoints frequently substitute for rare outcomes in research. The ability to learn about completed suicides by investigating more readily available and proximate outcomes, such as suicide attempts, has obvious appeal. However, concerns with surrogates from the statistical science perspective exist, and mounting evidence from…

  14. Blockade of leukocyte haptokinesis and haptotaxis by ketoprofen, diclofenac and SC-560

    Directory of Open Access Journals (Sweden)

    Paskauskas Saulius

    2011-11-01

    Full Text Available Abstract Background Nonsteroidal anti-inflammatory drugs (NSAID represent a one of the most widely used anti-inflammatory substances. Their anti-inflammatory effects are mainly based on inhibition of cyclooxygenase. The potential direct effect of NSAID on leukocyte migration was poorly investigated. Using time-lapse microscopy and 96-well fluorescence-based assay, we studied the effect of three different NSAID, ketoprofen, diclofenac and SC-560, on leukocyte haptokinesis and haptotaxis in vivo and in vitro. Results NSAID induced an immediate inhibiting effect on leukocyte migration both in vitro and in vivo. This effect was dose-dependent and was not restricted to a specific type of leukocytes. The inhibition of leukocyte migration by NSAID was partially re-stored after removal of inhibiting agent. Only complete blockade of leukocyte migration was accompanied by a strong reduction of [Ca2+]i. Conclusions NSAID strongly supress leukocyte migration. The results of the present study may have important clinical implications since blockade of leukocyte migration can be achieved after topical application of NSAID.

  15. Protective effects of combined β-caryophyllene and silymarin against ketoprofen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Kelany, Mohamed Elsayed; Abdallah, Mohamed Abdelmohsen

    2016-07-01

    Ketoprofen (Ket), widely utilized in treatment of many inflammatory disorders, is found to induce liver toxicity especially with overdose. This study aimed to evaluate the possible protective effects of concomitant β-caryophyllene (Cary) and silymarin (Sily) against Ket-induced hepatotoxicity in rats. Forty adult male albino rats were divided into 5 groups (each n = 8): the control group received distilled water for 6 weeks; the Ket-treated group received distilled water for 5 weeks and Ket in a dose of 8 mg·kg(-1)·day(-1) p.o. for the 6th week; the Cary + Ket treated group received Cary in a dose of 200 mg·kg(-1)·day(-1) orally for 6 weeks and Ket for the 6th week; the Sily + Ket treated group received Sily in the dose of 150 mg·kg(-1)·day(-1) for 6 weeks and Ket for the 6th week; and the Cary + Sily + Ket treated group received Sily and Cary for 6 weeks and Ket for the 6th week. At end of the experiment, serum ALT, AST, and albumin and liver total antioxidant capacity (t.TAC) and malondialdehyde (t.MDA) were measured in all rats. Ket increased serum ALT and AST and t.MDA and decreased t.TAC. Cary and Sily improved these changes. Combined Cary and Sily restored these liver changes to nearly normal. Combined Cary and Sily is hepatoprotective, with the ability to scavenge oxidants against Ket-induced hepatotoxicity in rats.

  16. Determination of ketoprofen in ketoprofen gel by RP-HPLC%RP-HPLC法测定酮洛芬凝胶中药物含量

    Institute of Scientific and Technical Information of China (English)

    石莉; 张晶; 李乐; 沙延淳; 邓波; 杨祝仁; 杨红玉

    2014-01-01

    Objective To establish a RP-HPLC method for the determination of ketoprofen in ketoprofen gel. Methods The separation was performed with a Diamonsil C18 column (4. 6 mm × 200 mm,5 μm) at room tempera-ture,with the mobile phase of 0. 01 mol/L potassium phosphate (adjust with phosphoric acid to pH value of 3. 0)-ace-tonitrile (50∶50). The flow rate was 1 mL/min. Ketoprofen was detected at 255 nm. Results There was a good linear relationship between A and concentration over the range of 0. 525~1. 575 μg (r=0. 999 9,n=5). The average recov-ery was 98. 41%,RSD was 1. 35%. After light irradiation,the content of ketoprofen decreased obviously and the impu-rity A ketoprofen increased significantly. Conclusion This method is applicable for the determination of ketoprofen in ketoprofen gel.%目的:建立酮洛芬凝胶中药物含量测定的方法,并明确光照对含量测定的影响。方法采用Diamonsil ODS柱(4.6 mm ×200 mm,5μm);流动相为0.01 mol/L磷酸二氢钾溶液(用磷酸调pH值至3.0)-乙腈(50∶50),流速1.0 mL/min,检测波长为255 nm,柱温为室温。结果在本试验条件下,酮洛芬凝胶中与辅料及有关物质分离度均符合要求,酮洛芬进样量在0.525~1.575μg范围内线性关系良好(r=0.9999,n=5),平均回收率为98.41%,RSD为1.35%(n=3)。经光照,酮洛芬含量明显降低,杂质A明显增加,杂质A为酮洛芬的光照降解产物。结论本方法简单、快捷,可用于酮洛芬凝胶中药物含量的测定。

  17. A pharmacokinetic comparison of meloxicam and ketoprofen following oral administration to healthy dogs.

    Science.gov (United States)

    Montoya, L; Ambros, L; Kreil, V; Bonafine, R; Albarellos, G; Hallu, R; Soraci, A

    2004-07-01

    Ketoprofen (KTP) and meloxicam (MLX) are non-steroidal anti-inflamatory drugs used extensively in veterinary medicine. The pharmacokinetics of these drugs were studied in eight dogs following a single oral dose of 1 mg/kg of KTP as a racemate or 0.2 mg/kg of MLX. The concentrations of the drugs in plasma were determined by high-performance liquid chromatography (HPLC). There were differences between the disposition curves of the KTP enantiomers, confirming that the pharmacokinetics of KTP is enantioselective. (S)-(+)-KTP was the predominant enantiomer; the S:R ratio in the plasma increased from 2.58 +/- 0.38 at 15 min to 5.72 +/- 2.35 at 1 h. The area under the concentration time curve (AUC) of (S)-(+)-KTP was approximately 6 times greater than that of (R)-(-)-KTP. The mean (+/- SD) pharmacokinetic parameters for (S)-(+)-KTP were characterized as Tmax = 0.76 +/- 0.19 h, Cmax = 2.02 +/- 0.41 microg/ml, t1/2el = 1.65 +/- 0.48 h, AUC = 6.06 +/- 1.16 microg.h/ml, Vd/F = 0.39 +/- 0.07 L/kg, Cl/F = 170 +/- 39 ml/(kg.h). The mean (+/- SD) pharmacokinetic parameters of MLX were Tmax = 8.5 +/- 1.91 h, Cmax = 0.82 +/- 0.29 microg/ml, t1/2lambda(z) = 12.13 +/- 2.15 h, AUCinf = 15.41 +/- 1.24 microg.h/ml, Vd/F = 0.23 +/- 0.03 L/ kg, and Cl/F = 10 +/- 1.4 ml/(kg.h). Our results indicate significant pharmacokinetic differences between MLX and KTP after therapeutic doses.

  18. Ketoprofen-loaded pomegranate seed oil nanoemulsion stabilized by pullulan: Selective antiglioma formulation for intravenous administration.

    Science.gov (United States)

    Ferreira, Luana M; Cervi, Verônica F; Gehrcke, Mailine; da Silveira, Elita F; Azambuja, Juliana H; Braganhol, Elizandra; Sari, Marcel H M; Zborowski, Vanessa A; Nogueira, Cristina W; Cruz, Letícia

    2015-06-01

    This study aimed to prepare pomegranate seed oil nanoemulsions containing ketoprofen using pullulan as a polymeric stabilizer, and to evaluate antitumor activity against in vitro glioma cells. Formulations were prepared by the spontaneous emulsification method and different concentrations of pullulan were tested. Nanoemulsions presented adequate droplet size, polydispersity index, zeta potential, pH, ketoprofen content and encapsulation efficiency. Nanoemulsions were able to delay the photodegradation profile of ketoprofen under UVC radiation, regardless of the concentration of pullulan. In vitro release study indicates that nanoemulsions were able to release approximately 95.0% of ketoprofen in 5h. Free ketoprofen and formulations were considered hemocompatible at 1 μg/mL, in a hemolysis study, for intravenous administration. In addition, a formulation containing the highest concentration of pullulan was tested against C6 cell line and demonstrated significant activity, and did not reduce fibroblasts viability. Thus, pullulan can be considered an interesting excipient to prepare nanostructured systems and nanoemulsion formulations can be considered promising alternatives for the treatment of glioma.

  19. Stereoselective binding of mexiletine and ketoprofen enantiomers with human serum albumin domains

    Institute of Scientific and Technical Information of China (English)

    Da SHI; Yin-xiu JIN; Yi-hong TANG; Hai-hong HU; Si-yun XU; Lu-shanYU; Hui-di JIANG; Su ZENG

    2012-01-01

    To investigate the stereoselective binding of mexiletine or ketoprofen enantiomers with different recombinant domains of human serum albumin (HSA).Methods:Three domains (HSA DOM Ⅰ,Ⅱ and Ⅲ) were expressed in Pichia pastoris GS115 cells.Blue Sepharose 6 Fast Flow was employed to purify the recombinant HSA domains.The binding properties of the standard ligands,digitoxin,phenylbutazone and diazepam,and the chiral drugs to HSA domains were investigated using ultrafiltration.The concentrations of the standard ligands,ketoprofen and mexiletine were analyzed with HPLC.Results:The recombinant HSA domains were highly purified as shown by SDS-PAGE and Western blotting analyses,The standard HSA ligands digitoxin,phenylbutazone and diazepam selectively binds to DOM Ⅰ,DOM Ⅱ and DOM Ⅲ,respectively.For the chiral drugs,R-ketoprofen showed a higher binding affinity toward DOM Ⅲ than S-ketoprofen,whereas S-mexiletine bound to DOM Ⅱ with a greater affinity than R-mexiletine.Conclusion:The results demonstrate that HSA DOM Ⅲ possesses the chiral recognition ability for the ketoprofen enantiomers,whereas HSA DOM Ⅱ possesses that for the mexiletine enantiomers.

  20. Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice

    Directory of Open Access Journals (Sweden)

    C.M. Souza

    2014-10-01

    Full Text Available Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106 cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10. The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker and for CD31 (blood vessel marker. Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy.

  1. Central and peripheral actions of the NSAID ketoprofen on spinal cord nociceptive reflexes.

    Science.gov (United States)

    Herrero, J F; Parrado, A; Cervero, F

    1997-10-01

    Ketoprofen is a non-steroidal antiinflammatory drug (NSAID) which provides effective analgesia in situations of pain provoked by tissue inflammation. However, the location of its analgesic effects, (peripheral tissues versus central nervous system), have not been clearly identified and separated. In the present study the effectiveness of ketoprofen was examined in two different types of experiments: (i) Open field behavioural tests in conscious rats, and (ii) spinal cord nociceptive reflexes (single motor units) activated by electrical and thermal stimulation in chloralose anaesthetised rats. The experiments were performed in rats with carrageenan-induced inflammation of one hindpaw, or of one knee joint. The administration of ketoprofen significantly inhibited the reduction of exploratory movements caused by inflammation in open field experiments. Ketoprofen was also effective in depressing reflex activity evoked by electrical and noxious thermal stimulation of the skin, either in inflamed tissue or in normal tissue of monoarthritic animals. It was also effective in the reduction of reflex wind-up; a phenomenon in which the activity of spinal cord neurones increases progressively with high frequency electrical stimulation. We therefore conclude that ketoprofen has central as well as peripheral analgesic activity.

  2. Adsorption of clofibric acid and ketoprofen onto powdered activated carbon: effect of natural organic matter.

    Science.gov (United States)

    Gao, Yaohuan; Deshusses, Marc A

    2011-12-01

    The adsorption of two acidic pharmaceutically active compounds (PhACs), clofibric acid and ketoprofen, onto powdered activated carbon (PAC) was investigated with a particular focus on the influence of natural organic matter (NOM) on the adsorption of the PhACs. Suwannee River humic acids (SRHAs) were used as a substitute for NOM. Batch adsorption experiments were conducted to obtain adsorption kinetics and adsorption isotherms with and without SRHAs in the system. The adsorption isotherms and adsorption kinetics showed that the adsorption ofclofibric acid was not significantly affected by the presence of SRHAs at a concentration of 5 mg (as carbon) L(-1). An adsorption capacity of 70 to 140 mg g(-1) was observed and equilibrium was reached within 48 h. In contrast, the adsorption of ketoprofen was markedly decreased (from about 120 mg g(-1) to 70-100 mg g(-1)) in the presence of SRHAs. Higher initial concentrations of clofibric acid than ketoprofen during testing may explain the different behaviours that were observed. Also, the more hydrophobic ketoprofen molecules may have less affinity for PAC when humic acids (which are hydrophilic) are present. The possible intermolecular forces that could account for the different behaviour of clofibric acid and ketoprofen adsorption onto PAC are discussed. In particular, the relevance of electrostatic forces, electron donor-acceptor interaction, hydrogen bonding and London dispersion forces are discussed

  3. Solid-state characterization of amorphous and mesomorphous calcium ketoprofen.

    Science.gov (United States)

    Atassi, Faraj; Mao, Chen; Masadeh, Ahmad S; Byrn, Stephen R

    2010-09-01

    This article is concerned with exploring the application of pair distribution in pharmaceutical analysis. The solid-state characterization of amorphous and mesomorphous (liquid crystalline) calcium ketoprofen is used as an example and the structures of the amorphous and mesomorphous phases of calcium ketoprofen are compared to that of the crystalline phase. An approach to calculating the optimal experimental parameters in pair distribution function (PDF) analysis as well as a suggested method to help assign the many different peaks in a PDF diagram of an organic material are discussed. The studied salts were analyzed by X-ray powder diffraction (XRPD), single crystal X-ray diffraction, Raman spectroscopy, polarized light microscopy (PLM), solid-state NMR (SSNMR), variable-temperature SSNMR, and PDF. Raman and SSNMR were useful techniques in identifying and differentiating the crystalline phase from the other two phases but failed, alone, to differentiate between the amorphous and mesomorphous phases. The absence of significant changes in chemical shifts in SSNMR and peak shifts in Raman spectra suggested that the differences in the molecular environment of the major chemical groups in the amorphous and mesomorphous phases were minimal. However, the broadening of the Raman and SSNMR peaks in the noncrystalline phases indicated an increase in the disorder in these systems. PDF analysis of the disordered phases revealed that upon dehydration or quench cooling where the system transformed from crystalline to become disordered, the calcium-calcium and calcium-oxygen (oxygen of the carboxylic acid) distances remained intact meanwhile the rest of the molecule became disordered. The preliminary results from variable-temperature SSNMR showed two different T(1) relaxation time profiles for the amorphous and mesomorphous phases. This was consistent with the hypothesis that part of the molecule remained ordered while the rest of the molecule became disordered and the amorphous

  4. Nanosized ethosomes bearing ketoprofen for improved transdermal delivery.

    Science.gov (United States)

    Chourasia, Manish K; Kang, Lifeng; Chan, Sui Yung

    2011-05-01

    The potential of ethosomes for delivering ketoprofen via skin was evaluated. The ethosomes were prepared, optimized and characterized. Vesicular shape, size and entrapment efficiency were determined by transmission electron microscopy, dynamic light scattering and minicolumn centrifugation technique, respectively. Vesicle sizes varied from 120.3±6.1 to 410.2±21.8 nm depending on the concentrations of soya phosphatidyl choline (SPC) and ethanol. Entrapment efficiency increased with concentrations of SPC and ethanol. The formulations exhibited entrapment efficiencies of 42-78%. In vitro release through cellophane membrane showed sustained release of drug from ethosomal formulations in contrast to hydroalcoholic drug solution (HA), which released most of the drug within 2-3 h. In vitro drug permeation across human skin revealed improved drug permeation and higher transdermal flux with ethosomal formulations compared to hydroethanolic drug solution. Kinetics of in vitro skin permeation showed zero order drug release from formulations. Based on in vitro transdermal flux, the estimated steady state in vivo plasma concentration from ethosomes attained therapeutic drug levels whereas hydroalcoholic drug solution exhibited sub therapeutic drug concentration with a patch size of 50 cm(2). Skin permeation of ethosomal formulations assessed by confocal microscopy revealed enhanced permeation of Rhodamine 123 loaded formulation in comparison to the hydroalcoholic solution.

  5. Investigation of ketoprofen binding to human serum albumin by spectral methods

    Science.gov (United States)

    Bi, Shuyun; Yan, Lili; Sun, Yantao; Zhang, Hanqi

    2011-01-01

    The binding of ketoprofen with human serum albumin (HSA) was studied by fluorescence and absorption spectroscopic methods. Quenching of fluorescence of HSA was found to be a static quenching process. At 288.15, 298.15, 308.15 and 318.15 K, the binding constants and binding sites were obtained. The effects of Cu 2+, Al 3+, Ca 2+, Pb 2+ and K + on the binding at 288.15 K were also studied. The thermodynamic parameters, Δ H, Δ G and Δ S were got and the main sort of acting force between ketoprofen and HSA was studied. Based on the Förster's theory of non-radiation energy transfer, the binding average distance, r, between the acceptor (ketoprofen) and the donor (HSA) was calculated.

  6. Effect of phonophoresis on skin permeation of commercial anti-inflammatory gels: sodium diclofenac and ketoprofen.

    Science.gov (United States)

    Souza, Jaqueline; Meira, Alianise; Volpato, Nadia Maria; Mayorga, Paulo; Gottfried, Carmem

    2013-09-01

    This study evaluated the use of ultrasound in combination with the commercial anti-inflammatory drugs ketoprofen and sodium diclofenac, according to the parameters used in physiotherapy. Ketoprofen and sodium diclofenac were used in the Franz diffusion cell model adapted to an ultrasound transducer in three conditions: no ultrasound, one application of ultrasound and two applications of ultrasound. High-performance liquid chromatography was used to quantify the total amount of drug permeating skin per unit area, as well as flux and latency. The results showed that for ketoprofen, the amount of drug permeating skin and flux increased with two ultrasound applications. Permeation of sodium diclofenac decreased in the presence of ultrasound. Ultrasound parameters and drug properties must be considered in the use of phonophoresis.

  7. Ketoprofen spray-dried microspheres based on Eudragit RS and RL: study of the manufacturing parameters.

    Science.gov (United States)

    Rassu, Giovanna; Gavini, Elisabetta; Spada, Gianpiera; Giunchedi, Paolo; Marceddu, Salvatore

    2008-11-01

    The preparation of ketoprofen spray-dried microspheres can be affected by the long drug recrystallization time. Polymer type and drug-polymer ratio as well as manufacturing parameters affect the preparation. The purpose of this work was to evaluate the possibility to obtain ketoprofen spray-dried microspheres using the Eudragit RS and RL; the influence of the spray-drying parameters on morphology, dimension, and physical stability of microspheres was studied. Ketoprofen microspheres based on Eudragit blend can be prepared by spray-drying and the nebulization parameters do not influence significantly particle properties; nevertheless, they can be affected by drying and storage methods. No effect of the container material is found.

  8. Molecular dynamics in liquid and glassy states of non-steroidal anti-inflammatory drug: ketoprofen.

    Science.gov (United States)

    Sailaja, U; Shahin Thayyil, M; Krishna Kumar, N S; Govindaraj, G

    2013-05-13

    Ketoprofen is a well known nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. It acts by inhibiting the body's production of prostaglandin. The molecular mobility of amorphous ketoprofen has been investigated by broadband dielectric spectroscopy (BDS) covering wide temperature and frequency range. Multiple relaxation processes were observed. Besides the primary α-relaxation, one secondary relaxation, γ-have been identified. The γ-process visible in the dielectric spectra at very low temperature is non-JG relaxation, and has an activation energy E=37.91 kJ/mol typical for local mobility. Based on Ngai's coupling model smaller n or a larger Kohlrausch exponent (1-n) of the α-relaxation associated with larger τβ (Tg). In the case of ketoprofen we conclude that the secondary relaxation (β) emerging from intermolecular motions, is hidden under the dominant α-peak. The temperature dependence of the relaxation time of the α-process can be described over the entire measured range by a single Vogel-Fulcher-Tammann (VFT) equation. From VFT fits, the glass transition temperature (Tg) was estimated as 267.07 K, and a fragility or steepness index m=86.57 was calculated, showing that ketoprofen is a fragile glass former. Our differential scanning calorimetry (DSC) study shows that ketoprofen is a non-crystallizing compound. To confirm the hydrogen bond patterns of ketoprofen FTIR spectroscopy was applied in both crystalline and amorphous phases. Solubility test performed at 37 °C proved that amorphous phase is more soluble than the crystalline phase.

  9. PERILAKU DISOLUSI KETOPROFEN DAN INDOMETASIN FARNESIL TERSALUT GEL KITOSAN-GG

    Directory of Open Access Journals (Sweden)

    Purwantiningsih Sugita

    2008-08-01

    Full Text Available Chitosan, a modification of shrimp-shell waste, has been utilized as microcapsule. However, it's fragile gel property needs to be strengthened by adding glutaraldehyde (glu and natural hydrocolloid guar gum (gg. This research's purposes were to determine rheological properties of chitosan-guar gum gel, to study diffusion and dissolution behaviour of ketoprofen and infar through optimum chitosan-guar gum gel membrane and microcapsule, respectively, and to test the coating stability of both medicines by the gel microcapsules, which are new drug's preparation, to determine their shelf lives and to predict the degradation mechanisms. This research was designed in six (6 steps: (1 chitin isolation and chitosan synthesis; (2 synthesis and optimization of chitosan-guar gum gel membrane; (3 in vitro study of ketoprofen and infar diffusion behaviour through the optimum membrane; (4 synthesis and optimization of chitosan-guar gum gel microcapsule to coat ketoprofen and infar; (5 in vitro study of ketoprofen and infar dissolution behaviour from the optimum microcapsule; and (6 physical and chemical microcapsule stability test using relative humidity (RH and temperature controlled climatic chamber method. Studies on ketoprofen diffusion through chitosan-guar gum membrane showed that the formation of membrane small pores were appeared to be caused by membrane swelling, which was supported by the forcing force resulted from the difference of ketoprofen concentrations in the diffusion cells and from the temperature increase. This unique pore opening process is excellent for drug delivery process as a microcapsule. Spray drying process had successfully coated ketoprofen and infar in chitosan-guar gum microcapsule. Optimization by using Minitab Release 14 software showed that among the microcapsule compositions studied, [gg] and [glu] of 0.35% (w/v and 3.75% (v/v, respectively were optimum to coat ketoprofen, whereas [gg] and [glu] of 0.05% (w/v and 4.00% (v

  10. Encapsulated Ketoprofen by Chitosan-Alginat based on Type and Variation of Tween 80 and Span 80 Concentration.

    Directory of Open Access Journals (Sweden)

    Tuti Wukirsari

    2010-11-01

    Full Text Available Encapsulated Ketoprofen by Chitosan-Alginat based on Type and Variation of Tween 80 and Span 80Concentration. Ketoprofen has been encapsulated by chitosan-alginate based on types of surfactant and it’sconcentration. The variations of concentration either Tween 80 (polietilena sorbitanmonooleat or Span 80(sorbitanmonooleat that used were around (1- 3% concentrations with stirring around (15-60 minutes. The using ofTween 80 resulted efficiency of encapsulated ketoprofen and nano particle size (100-1000 nm are higher than Span 80.

  11. Substituent Effects on the Photodeprotection Reactions of Selected Ketoprofen Derivatives in Phosphate Buffered Aqueous Solutions

    Science.gov (United States)

    Liu, Mingyue; Li, Ming-De; Huang, Jinqing; Li, Tianlu; Liu, Han; Li, Xuechen; Phillips, David Lee

    2016-02-01

    Photodeprotection is an important reaction that has been attracting broad interest for use in a variety of applications. Recent advances in ultrafast and vibrational time-resolved spectroscopies can facilitate obtaining data to help unravel the reaction mechanisms involving in the photochemical reactions of interest. The kinetics and reaction mechanisms for the photodeprotection reactions of ketoprofen derivatives containing three different substituents (ibuprofen, Br and I) were investigated by femtosecond transient absorption (fs-TA) and nanosecond time-resolved resonance Raman (ns-TR3) spectroscopy methods in phosphate buffered solutions (PBS). Fs-TA allows us to detect the decay kinetics of the triplet species as the key precursor for formation of a carbanion species for three different substituents attached to ketoprofen. To characterize the structural and electronic properties of the corresponding carbanion and triplet intermediates, TR3 spectroscopic experiments were conducted. The transient spectroscopy work reveals that the different substituents affect the photodecarboxylation reaction to produce carbon dioxide which in turn influences the generation of the carbanion species which determines the rate of the photorelease of the functional groups attached on the ketoprofen parent molecule. The fingerprint TR3 spectroscopy results suggest that ketoprofen derivatives may be deactivated to produce a triplet carbanion when increasing the atom mass of the halogen atoms.

  12. Ecotoxicity of ketoprofen, diclofenac, atenolol and their photolysis byproducts in zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Diniz, M.S., E-mail: mesd@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Salgado, R., E-mail: r.salgado@campus.fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); ESTS-IPS, Escola Superior de Tecnologia de Setúbal do Instituto Politécnico de Setúbal, Rua Vale de Chaves, Campus do IPS, Estefanilha, 2910-761 Setúbal (Portugal); Pereira, V.J., E-mail: vanessap@itqb.unl.pt [Instituto de Biologia Experimental e Tecnológica (IBET), Av. da República (EAN), 2784-505 Oeiras (Portugal); Instituto de Tecnologia Química e Biológica (ITQB)—Universidade Nova de Lisboa (UNL), Estação Agronómica Nacional, Av. da República, 2780-157 Oeiras (Portugal); Carvalho, G., E-mail: gs.carvalho@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Instituto de Biologia Experimental e Tecnológica (IBET), Av. da República (EAN), 2784-505 Oeiras (Portugal); Oehmen, A., E-mail: a.oehmen@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Reis, M.A.M., E-mail: amr@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Noronha, J.P., E-mail: jpnoronha@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)

    2015-02-01

    The occurrence of pharmaceutical compounds in wastewater treatment plants and surface waters has been detected worldwide, constituting a potential risk for aquatic ecosystems. Adult zebrafish, of both sexes, were exposed to three common pharmaceutical compounds (atenolol, ketoprofen and diclofenac) and their UV photolysis by-products over seven days. The results show that diclofenac was removed to concentrations < LOD after 5 min of UV irradiation. The oxidative stress response of zebrafish to pharmaceuticals and their photolysis by-products was evaluated through oxidative stress enzymes (glutathione-S-transferase, catalase, superoxide dismutase) and lipid peroxidation. Results suggest that the photolysis by-products of diclofenac were more toxic than those from the other compounds tested, showing an increase in GST and CAT levels, which are also supported by higher MDA levels. Overall, the toxicity of waters containing atenolol and ketoprofen was reduced after the parent compounds were transformed by photolysis, whereas the toxicity increased significantly from the by-products generated through diclofenac photolysis. Therefore, diclofenac photolysis would possibly necessitate higher irradiation time to ensure that the associated by-products are completely degraded to harmless form(s). - Highlights: • Toxicity evaluated for 3 common pharmaceuticals (atenolol, ketoprofen and diclofenac). • Toxicity assessed for the pharmaceuticals and UV photolysis by-products in zebrafish. • Diclofenac photolysis by-products are more toxic than the parent compound. • Ketoprofen and atenolol show stronger oxidative stress response than by-products. • UV photolysis should ensure full removal of diclofenac metabolites to avoid toxicity.

  13. Effect of ketoprofen and indomethacin on methotrexate pharmacokinetics in mice plasma and tumor tissues.

    Science.gov (United States)

    Elmorsi, Yasmine M; El-Haggar, Sahar M; Ibrahim, Osama M; Mabrouk, Mokhtar M

    2013-03-01

    Methotrexate (MTX) has been used in combination with nonsteroidal anti-inflammatory drugs in the treatment of inflammatory diseases as well as malignancies. Severe adverse effects with this combination may occur, usually resulting from inhibition of renal transporters. Solid Ehrlich carcinoma was experimentally induced by implantation of Ehrlich ascites Carcinoma cells subcutaneously into the thigh of mice, and after 30 days, mice were divided into three groups: Group I that served as control group received MTX (50 mg/kg, i.p.); Group II received ketoprofen (100 mg/kg, i.p.) and then after half an hour received MTX (50 mg/kg, i.p.); Group III received indomethacin (10 mg/kg, i.p.) and then after half an hour received MTX (50 mg/kg, i.p.). Plasma and tissue samples were collected at different time points and then MTX concentrations were determined by HPLC. The injection of ketoprofen or indomethacin before MTX injection resulted in significant increase in the AUC and CPmax of MTX (p ketoprofen. The study showed that administration of ketoprofen or indomethacin prior to MTX caused significant decrease in MTX elimination and significant increase in MTX extent of absorption which may lead to severe adverse effects if coadministered in human.

  14. First principles study on the molecular structure and vibrational spectra of ketoprofen

    Science.gov (United States)

    Liu, Lekun; Gao, Hongwei

    2012-11-01

    The aim of this work was to compare the performance of different DFT methods at different basis sets in predicting geometry and vibration spectrum of ketoprofen. The molecular geometry and vibrational frequencies of ketoprofen have been calculated using five different density function theory (DFT) methods, including LSDA, B3LYP, mPW1PW91, B3PW91 and HCTH, with various basis sets, including 6-311G, 6-311+G, 6-311++G, 6-311+G (d, p) and 6-311++G (2d, 2p). The results indicate that mPW1PW91/6-311++G (2d, 2p) level is clearly superior to all the remaining density functional methods in predicting the bond lengths and bond angles of ketoprofen. Mean absolute deviations between the calculated harmonic and observed fundamental vibration frequencies for each method shows that LSDA/6-311G method is the best to predict vibrational spectra of ketoprofen comparing other DFT methods.

  15. Comparative evaluation of polymeric and waxy microspheres for combined colon delivery of ascorbic acid and ketoprofen.

    Science.gov (United States)

    Maestrelli, F; Zerrouk, N; Cirri, M; Mura, P

    2015-05-15

    The goal of this work was to combine the ketoprofen anti-inflammatory effect with the ascorbic acid antioxidant properties for a more efficient treatment of colonic pathologies. With this aim, microspheres (MS) based on both waxy materials (ceresine, Precirol(®) and Compritol(®)) or hydrophilic biopolymers (pectine, alginate and chitosan) loaded with the two drugs were developed, physicochemically characterized and compared in terms of entrapment efficiency, in vitro release profiles, potential toxicity and drug permeation properties across the Caco-2 cell line. Waxy MS revealed an high encapsulation efficiency of ketoprofen but a not detectable entrapment of ascorbic acid, while polymeric MS showed a good entrapment efficiency of both drugs. All MS need a gastro-resistant coating, to avoid any premature release of the drugs. Ketoprofen release rate from polymeric matrices was clearly higher than from the waxy ones. In contrast, the ASC release rate was higher, due to its high hydro-solubility. Cytotoxicity studies revealed the safety of all the formulations. Transport studies showed that the ketoprofen apparent permeability increased, when formulated with the different MS. In conclusion, only polymeric MS enabled an efficient double encapsulation of both the hydrophilic and lipophilic drugs, and, in addition, presented higher drug release rate and stronger enhancer properties.

  16. Photodegradation kinetics and transformation products of ketoprofen, diclofenac and atenolol in pure water and treated wastewater

    Energy Technology Data Exchange (ETDEWEB)

    Salgado, R. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); ESTS-IPS, Escola Superior de Tecnologia de Setúbal do Instituto Politécnico de Setúbal, Rua Vale de Chaves, Campus do IPS, Estefanilha, 2910-761 Setúbal (Portugal); Pereira, V.J. [Instituto de Biologia Experimental e Tecnológica (IBET), Av. da República (EAN), 2784-505 Oeiras (Portugal); Instituto de Tecnologia Química e Biológica (ITQB) – Universidade Nova de Lisboa (UNL), Av. da República, Estação Agronómica Nacional, 2780-157 Oeiras, 5 Portugal (Portugal); Carvalho, G., E-mail: gs.carvalho@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Instituto de Biologia Experimental e Tecnológica (IBET), Av. da República (EAN), 2784-505 Oeiras (Portugal); Soeiro, R. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Gaffney, V.; Almeida, C. [Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculdade de Farmácia da Universidade de Lisboa (FFUL), Av. Prof. Gama Pinto, 1600-049 Lisboa (Portugal); Cardoso, V. Vale; Ferreira, E.; Benoliel, M.J. [Empresa Portuguesa das Águas Livres, S.A., Direcção de Controlo de Qualidade da Água, Laboratório Central, Avenida de Berlim, 15, 1800-031 Lisboa (Portugal); and others

    2013-01-15

    Highlights: ► Direct UV photolysis of 3 pharmaceuticals in pure and waste water was investigated. ► Ketoprofen has higher photodegradion kinetics, followed by diclofenac and atenolol. ► MP/UV photodegradation products were identified for the 3 compounds. ► Photodegradation pathways were proposed to explain the obtained products. ► The persistent photoproducts were identified for each compound. -- Abstract: Pharmaceutical compounds such as ketoprofen, diclofenac and atenolol are frequently detected at relatively high concentrations in secondary effluents from wastewater treatment plants. Therefore, it is important to assess their transformation kinetics and intermediates in subsequent disinfection processes, such as direct ultraviolet (UV) irradiation. The photodegradation kinetics of these compounds using a medium pressure (MP) lamp was assessed in pure water, as well as in filtered and unfiltered treated wastewater. Ketoprofen had the highest time- and fluence-based rate constants in all experiments, whereas atenolol had the lowest values, which is consistent with the corresponding decadic molar absorption coefficient and quantum yield. The fluence-based rate constants of all compounds were evaluated in filtered and unfiltered wastewater matrices as well as in pure water. Furthermore, transformation products of ketoprofen, diclofenac and atenolol were identified and monitored throughout the irradiation experiments, and photodegradation pathways were proposed for each compound. This enabled the identification of persistent transformation products, which are potentially discharged from WWTP disinfection works employing UV photolysis.

  17. Failure of Ketoprofen and Interferon Combination Therapy to Improve Interferon-Resistant Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Frank H Anderson

    1997-01-01

    Full Text Available Preliminary reports suggest that patients with interferon (IFN-resistant chronic hepatitis C respond better to a combination of IFN-α and nonsteroidal anti-inflammatory drugs than to IFN alone. The efficacy of IFN combined with ketoprofen in the treatment of patients with IFN-resistant chronic hepatitis C was evaluated. Seventeen patients, nonresponsive after at least six months of treatment with IFN-α2b and subsequently treated with the combination of IFN-α2b plus ketoprofen for four months, were studied. Serum aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST] and serum hepatitis C virus (HCV RNA were analyzed before and throughout treatment. No patient normalized serum aminotransferases after combination therapy. There were no significant differences in mean serum ALT and AST levels before and after ketoprofen intervention. Serum HCV RNA became undetectable after treatment in only one patient, but was detectable again three months after treatment cessation. These results provide no convincing evidence that the combination of IFN-α2b with ketoprofen improves the response to IFN in patients nonresponsive to IFN alone.

  18. Failure of ketoprofen and interferon combination therapy to improve interferon-resistant chronic hepatitis C.

    Science.gov (United States)

    Anderson, F H; Zeng, L; Yoshida, E M; Rock, N R

    1997-01-01

    Preliminary reports suggest that patients with interferon (IFN)-resistant chronic hepatitis C respond better to a combination of IFN-alpha and nonsteroidal anti-inflammatory drugs than to IFN alone. The efficacy of IFN combined with ketoprofen in the treatment of patients with IFN-resistant chronic hepatitis C was evaluated. Seventeen patients, nonresponsive after at least six months of treatment with IFN-alpha 2b and subsequently treated with the combination of IFN-alpha 2b plus ketoprofen for four months, were studied. Serum aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and serum hepatitis C virus (HCV) RNA were analyzed before and throughout treatment. No patient normalized serum aminotransferases after combination therapy. There were no significant differences in mean serum ALT and AST levels before and after ketoprofen intervention. Serum HCV RNA became undetectable after treatment in only one patient, but was detectable again three months after treatment cessation. These results provide no convincing evidence that the combination of IFN-alpha 2b with ketoprofen improves the response to IFN in patients nonresponsive to IFN alone.

  19. Failure of Ketoprofen and Interferon Combination Therapy to Improve Interferon-Resistant Chronic Hepatitis C

    OpenAIRE

    Frank H Anderson; Lecheng Zeng; Yoshida, Eric M; Natalie R Rock

    1997-01-01

    Preliminary reports suggest that patients with interferon (IFN)-resistant chronic hepatitis C respond better to a combination of IFN-α and nonsteroidal anti-inflammatory drugs than to IFN alone. The efficacy of IFN combined with ketoprofen in the treatment of patients with IFN-resistant chronic hepatitis C was evaluated. Sevent...

  20. Cobra Venom Factor and Ketoprofen Abolish the Antitumor Effect of Nerve Growth Factor from Cobra Venom.

    Science.gov (United States)

    Osipov, Alexey V; Terpinskaya, Tatiana I; Kuznetsova, Tatiana E; Ryzhkovskaya, Elena L; Lukashevich, Vladimir S; Rudnichenko, Julia A; Ulashchyk, Vladimir S; Starkov, Vladislav G; Utkin, Yuri N

    2017-09-06

    We showed recently that nerve growth factor (NGF) from cobra venom inhibited the growth of Ehrlich ascites carcinoma (EAC) inoculated subcutaneously in mice. Here, we studied the influence of anti-complementary cobra venom factor (CVF) and the non-steroidal anti-inflammatory drug ketoprofen on the antitumor NGF effect, as well as on NGF-induced changes in EAC histological patterns, the activity of lactate and succinate dehydrogenases in tumor cells and the serum level of some cytokines. NGF, CVF and ketoprofen reduced the tumor volume by approximately 72%, 68% and 30%, respectively. The antitumor effect of NGF was accompanied by an increase in the lymphocytic infiltration of the tumor tissue, the level of interleukin 1β and tumor necrosis factor α in the serum, as well as the activity of lactate and succinate dehydrogenases in tumor cells. Simultaneous administration of NGF with either CVF or ketoprofen abolished the antitumor effect and reduced all other effects of NGF, whereas NGF itself significantly decreased the antitumor action of both CVF and ketoprofen. Thus, the antitumor effect of NGF critically depended on the status of the immune system and was abolished by the disturbance of the complement system; the disturbance of the inflammatory response canceled the antitumor effect as well.

  1. A new approach for preparing a controlled release ketoprofen tablets by using beeswax.

    Science.gov (United States)

    Uner, Melike; Gönüllü, Umit; Yener, Gülgün; Altinkurt, Turan

    2005-01-01

    Solid lipid ketoprofen micropellets (SLKM) at different drug/beeswax ratios [(1:1) and (1:2)] were prepared by emulsion congealing technique and then compressed into tablets. Ketoprofen in solid state was incorporated into the melted beeswax at 90 degrees C and the mixture was emulsified in the hot aqueous Tween 80 solution by stirring at a constant rate. The SLKM were obtained by cooling the coarse emulsion down to room temperature and filtering. Drug entrapment efficiency and particle size analysis by laser diffractometry (LD) were determined, and existence of a drug-lipid interaction was investigated by differential scanning calorimetry (DSC) on the SLKM, before being compressed into the tablets by direct compression method. Finally, in vitro release studies were performed and the release kinetics of the waxy tablets were calculated. A commercial ketoprofen retard tablet (reference: Profenid Retard 200 mg) was also examined to compare the release properties. While the data obtained from DSC were indicating absence of drug-lipid interaction in the SLKM, it was determined that 28.62% (+/-2.08), 38.60% (+/-1.91) and 47.00% (+/-1.82) of ketoprofen was released from the tablets containing (1:2) and (1:1) SLKM and Profenid Retard 200 mg in pH 7.4 phosphate buffer solution after 8 h, respectively.

  2. Application of dermal microdialysis for the evaluation of bioequivalence of a ketoprofen topical gel

    DEFF Research Database (Denmark)

    Tettey-Amlalo, Ralph Nii Okai; Kanfer, Isadore; Skinner, Michael F

    2008-01-01

    was scanned by ultrasound to determine the implantation depth of these probes. Ketoprofen concentration in dialysates was determined by LC-MS/MS. The area under the curve obtained from the concentration-time profiles from pairs of application sites in each subject was evaluated in order to assess...

  3. Tailoring of ketoprofen particle morphology via novel crystallocoagglomeration technique to obtain a directly compressible material

    Directory of Open Access Journals (Sweden)

    Chavda Vikash

    2008-01-01

    Full Text Available Purpose: The purpose of this research was to develop a novel crystallo-co-agglomeration (CCA method for ketoprofen to obtain its directly compressible spherical agglomerates with improved flowability and compressibility. Methodology: Dichloromethane-water system containing polyethylene glycol (PEG 6000, polyvinyl alcohol (PVA, and hydroxypropylmethylcellulose (HPMC 100 Centi Poise was used as the crystallization system. Ketoprofen was crystallized from dichloromethane and agglomerated with talc. Experimental parameters (concentration of PEG, PVA, and HPMC; effect of temperature; and agitation speed were optimized. The agglomerates were evaluated for micrometric properties, mechanical properties, moisture content, compressibility, packability, and drug-release properties. The agglomerates were characterized by differential scanning calorimetry (DSC, powder x-ray diffraction (PXRD, infrared (IR spectroscopy, and scanning electron microscopy (SEM. Main Findings: Remarkable improvement in micromeritic properties (angle of repose < 22°, percentage compressibility < 10, and Hausner ratio near to 1 and compactibility (mean yield pressure 55-93 MPa enabled direct compression without any defect. Results of friability showed higher surface strength of agglomerates containing higher amount of talc. DSC, PXRD, and IR results showed no change in the crystalline form of ketoprofen. Dissolution study of batches KA, KB, KC, and KD(composition given in [Table 1] showed 90% drug release in 120, 180, 240, and 420 min respectively. Principal Conclusions: Crystallo-co-agglomeration process can be considered as a suitable alternative to conventional granulation process to obtain agglomerates of ketoprofen with improved micromeritic and compressibility parameters. The CCA technique can be used for the design of sustained-release ketoprofen talc agglomerates containing lower amounts of polymers.

  4. Ketoprofen-eluting biodegradable ureteral stents by CO2 impregnation: In vitro study.

    Science.gov (United States)

    Barros, Alexandre A; Oliveira, Carlos; Reis, Rui L; Lima, Estevão; Duarte, Ana Rita C

    2015-11-30

    Ureteral stents are indispensable tools in urologic practice. The main complications associated with ureteral stents are dislocation, infection, pain and encrustation. Biodegradable ureteral stents are one of the most attractive designs with the potential to eliminate several complications associated with the stenting procedure. In this work we hypothesize the impregnation of ketoprofen, by CO2-impregnation in a patented biodegradable ureteral stent previously developed in our group. The biodegradable ureteral stents with each formulation: alginate-based, gellan gum-based were impregnated with ketoprofen and the impregnation conditions tested were 100 bar, 2 h and three different temperatures (35 °C, 40 °C and 50 °C). The impregnation was confirmed by FTIR and DSC demonstrated the amorphization of the drug upon impregnation. The in vitro elution profile in artificial urine solution (AUS) during degradation of a biodegradable ureteral stent loaded with ketoprofen was evaluated. According to the kinetics results these systems have shown to be very promising for the release ketoprofen in the first 72 h, which is the necessary time for anti-inflammatory delivery after the surgical procedure. The in vitro release studied revealed an influence of the temperature on the impregnation yield, with a higher impregnation yield at 40 °C. Higher yields were also obtained for gellan gum-based stents. The non-cytotoxicity characteristic of the developed ketoprofen-eluting biodegradable ureteral stents was evaluated in L929 cell line by MTS assay which demonstrated the feasibility of this product as a medical device.

  5. [The preemptive action of ketoprofen. Randomized, double-blind study with gynecologic operations].

    Science.gov (United States)

    Likar, R; Krumpholz, R; Mathiaschitz, K; Pipam, W; Burtscher, M; Ozegovic, G; Breschan, C; Bernatzky, G; Sittl, R

    1997-03-01

    Ketoprofen exerts its clinical effect by inhibition of prostaglandin synthesis, but also acts as an NMDA-receptor antagonist by means of the kynurenic acid. Based on ketoprofen's supposed central mechanism of analgesia, we expected a preemptive effect, which was assessed by the present study. In a prospective, randomised, double-blind investigation of 48 patients undergoing gynaecological procedures (laparotomy, pelvioscopy), the first group received ketoprofen 2 mg/kg body weight i.v. 20 min before the beginning of surgery and placebo i.v. at the end of surgery. In the second group, placebo was administered first and ketoprofen at the end of surgery. Premedication and anaesthesia were standardised by protocol. The postoperative analgesic patient-controlled analgesia consumption by was also standardised (piritramide). Efficacy was assessed by visual analogue scale (VAS) and total requirement of analgesics within the first 24 postoperative hours. The time to the first request for postoperative analgesics was also recorded. Safety was assessed by continuous monitoring of vital parameters such as respiratory rate, heart rate, blood pressure, and oxygen saturation. The incidence and severity of adverse events was documented. There were no significant differences between the groups in demographic data or type or duration of surgery. The time to the first request for analgesic, VAS pain intensity, and analgesic consumption in the first 24 h post-surgery were not significantly different between the groups (t-test). Ketoprofen is an effective post-operative analgesic in combination with an opioid, but has no preemptive effect according to the results of this study.

  6. Revisiting algorithms for generating surrogate time series

    CERN Document Server

    Raeth, C; Papadakis, I E; Brinkmann, W

    2011-01-01

    The method of surrogates is one of the key concepts of nonlinear data analysis. Here, we demonstrate that commonly used algorithms for generating surrogates often fail to generate truly linear time series. Rather, they create surrogate realizations with Fourier phase correlations leading to non-detections of nonlinearities. We argue that reliable surrogates can only be generated, if one tests separately for static and dynamic nonlinearities.

  7. Preparation and Pharmacological Evaluation of Novel Orally Active Ester Prodrugs of Ketoprofen with Non-Ulcerogenic Property.

    Science.gov (United States)

    Dhakane, Valmik D; Thakare, Vishnu N; Dongare, Sakharam B; Bhale, Pravin S; Mule, Yoginath B; Bandgar, Babasaheb P; Chavan, Hemant V

    2016-06-01

    This study investigates anti-inflammatory activity with improved pharmacokinetic and non-ulcerogenic properties of various novel synthesized prodrugs of ketoprofen in experimental animals. Prodrugs 3a, 3f and 3k were found to possess significant anti-inflammatory activity with almost non-ulcerogenic potential than standard drug ketoprofen (1) in both normal and inflammation-induced rats. The experimental findings elicited higher AUC and plasma concentration at 1 and 2 h indicating improved oral bioavailability as compared to parent drug ketoprofen. These prodrugs are found to have no gastric ulceration with retained anti-inflammatory activity. Therefore, present experimental findings demonstrated significant improvement of various pharmacokinetic properties with non-ulcerogenic potential of ester prodrugs of ketoprofen.

  8. The effect of administering ketoprofen on the physiology and behavior of dairy cows following surgery to correct a left displaced abomasum.

    Science.gov (United States)

    Newby, Nathalie C; Pearl, David L; LeBlanc, Stephen J; Leslie, Ken E; von Keyserlingk, Marina A G; Duffield, Todd F

    2013-03-01

    Surgical correction of left displaced abomasum (LDA) is common in lactating dairy cattle. Despite the growing acceptance that abdominal surgery is painful, few cows are administered analgesia following LDA surgery. The objective of this research was to examine the effect of administering a label dose of ketoprofen on physiological and behavioral indicators of pain in dairy cattle. Holstein cows were enrolled in a field study following LDA surgery. Surgery was performed using the standing right flank (RF) approach or the paramedian (PARA) approach. Using a triple-blind randomized trial, each animal was assigned to receive either 3mg of ketoprofen/kg of body weight or saline (the equivalent volume) by intramuscular injection immediately following surgery and 24h postoperatively. Physiological parameters (heart rate, respiration rate, and rumen motility), blood β-hydroxybutyrate (BHBA) levels, and an assessment of cow attitude were measured on the day of surgery, and at 2 follow-up visits (visit 1=3 ± 0.9 d and visit 2=9 ± 1.2 d postsurgery; n=175). Milk production and culling were recorded for all cows enrolled in the study. Producers assessed their cows' attitudes and appetites daily for the first 3 d following surgery. A subset of cows (n=37) were fitted on the day of surgery with a 3-axis accelerometer on the hind leg to assess lying behavior. Continuous and binary outcome data were analyzed using multivariable mixed linear and mixed logistic models, respectively, with cow modeled as a random effect. Ketoprofen did not alter the physiological measures, BHBA levels, or behavioral outcomes measured. Cows subjected to RF surgery had longer lying times [model coefficient β=228.9 min; 95% confidence interval (CI): 122.2 to 335.6] in the first 3 d following surgery, and lower heart rates (β=-9.4 beats/min; 95% CI: -12 to -6.9 beats/min) at the follow-up visits, compared with animals that underwent PARA surgery. Regardless of surgical procedure, BHBA decreased from

  9. DEVELOPMENT OF AN ANALYTICAL METHOD FOR SPECTROPHOTOMETRIC ESTIMATION OF KETOPROFEN USING MIXED CO SOLVENCY APPROACH

    Directory of Open Access Journals (Sweden)

    R. Deveswaran et al.

    2012-04-01

    Full Text Available The present study demonstrates the use of mixed co solvency in the enhancement of solubility and estimation of ketoprofen, practically water insoluble dug and thus precludes the use of organic solvents. The selected solubilizers were sodium citrate (15%, PEG 400 (8% and polyvinyl pyrolidine (7%. Beer’s law was obeyed in the concentration range of 2-20µg/ml at wavelength of 256nm. The solubility of ketoprofen was increased by 30 folds in the mixed cos-solvents as compared to distilled water. The recovery study revealed that any small change in the drug concentration in the solution could be accurately determined by the proposed method. The low values of LOD and LOQ indicated good sensitivity of proposed method. The study proved that mixed co-solvency phenomenon is an effective technique in enhancement of aqueous solubility of poorly water soluble drugs and can be successfully employed for estimation of drugs in routine analysis of tablets.

  10. Nanoparticles containing ketoprofen and acrylic polymers prepared by an aerosol flow reactor method.

    Science.gov (United States)

    Eerikäinen, Hannele; Peltonen, Leena; Raula, Janne; Hirvonen, Jouni; Kauppinen, Esko I

    2004-09-23

    The purpose of this study was to outline the effects of interactions between a model drug and various acrylic polymers on the physical properties of nanoparticles prepared by an aerosol flow reactor method. The amount of model drug, ketoprofen, in the nanoparticles was varied, and the nanoparticles were analyzed for particle size distribution, particle morphology, thermal properties, IR spectroscopy, and drug release. The nanoparticles produced were spherical, amorphous, and had a matrix-type structure. Ketoprofen crystallization was observed when the amount of drug in Eudragit L nanoparticles was more than 33% (wt/wt). For Eudragit E and Eudragit RS nanoparticles, the drug acted as an effective plasticizer resulting in lowering of the glass transition of the polymer. Two factors affected the preparation of nanoparticles by the aerosol flow reactor method, namely, the solubility of the drug in the polymer matrix and the thermal properties of the resulting drug-polymer matrix.

  11. Photoallergic Contact Dermatitis due to Ketoprofen and Hydrogenated Rosin Glycerol Ester

    Directory of Open Access Journals (Sweden)

    Tomoko Rindo

    2010-04-01

    Full Text Available A topical application of a nonsteroidal anti-inflammatory drug (NSAID may induct an adverse reaction of photoallergic contact dermatitis. The occlusive usage may provoke concomitant photoallergic sensitizations to an NSAID and other ingredients. We describe a 58-year-old woman with photoallergic contact dermatitis from ketoprofen and hydrogenated rosin glycerol ester in the applied compress. Our case indicates that photopatch testing with all ingredients is required to verify the actual photoallergen(s.

  12. Effects of ketoprofen, morphine, and kappa opioids on pain-related depression of nesting in mice.

    Science.gov (United States)

    Negus, S Stevens; Neddenriep, Bradley; Altarifi, Ahmad A; Carroll, F Ivy; Leitl, Michael D; Miller, Laurence L

    2015-06-01

    Pain-related functional impairment and behavioral depression are diagnostic indicators of pain and targets for its treatment. Nesting is an innate behavior in mice that may be sensitive to pain manipulations and responsive to analgesics. The goal of this study was to develop and validate a procedure for evaluation of pain-related depression of nesting in mice. Male ICR mice were individually housed and tested in their home cages. On test days, a 5- × 5-cm Nestlet was subdivided into 6 pieces, the pieces were evenly distributed on the cage floor, and Nestlet consolidation was quantified during 100-minute sessions. Baseline nesting was stable within and between subjects, and nesting was depressed by 2 commonly used inflammatory pain stimuli (intraperitoneal injection of dilute acid; intraplantar injection of complete Freund adjuvant). Pain-related depression of nesting was alleviated by drugs from 2 classes of clinically effective analgesics (the nonsteroidal anti-inflammatory drug ketoprofen and the μ-opioid receptor agonist morphine) but not by a drug from a class that has failed to yield effective analgesics (the centrally acting kappa opioid agonist U69,593). Neither ketoprofen nor morphine alleviated depression of nesting by U69,593, which suggests that ketoprofen and morphine effects were selective for pain-related depression of nesting. In contrast to ketoprofen and morphine, the kappa opioid receptor antagonist JDTic blocked depression of nesting by U69,593 but not by acid or complete Freund adjuvant. These results support utility of this procedure to assess expression and treatment of pain-related depression in mice.

  13. Accelerated ketoprofen release from polymeric matrices: importance of the homogeneity/heterogeneity of excipient distribution.

    Science.gov (United States)

    Gue, E; Willart, J F; Muschert, S; Danede, F; Delcourt, E; Descamps, M; Siepmann, J

    2013-11-30

    Polymeric matrices loaded with 10-50% ketoprofen were prepared by hot-melt extrusion or spray-drying. Eudragit E, PVP, PVPVA and HPMC were studied as matrix formers. Binary "drug-Eudragit E" as well as ternary "drug-Eudragit E-PVP", "drug-Eudragit E-PVPVA" and "drug-Eudragit E-HPMC" combinations were investigated and characterized by optical macro/microscopy, SEM, particle size measurements, mDSC, X-ray diffraction and in vitro drug release studies in 0.1 M HCl. In all cases ketoprofen release was much faster compared to a commercially available product and the dissolution of the drug powder (as received). Super-saturated solutions were obtained, which were stable during at least 2 h. Importantly, not only the composition of the systems, but also their inner structure potentially significantly affected the resulting ketoprofen release kinetics: For instance, spray-drying ternary ketoprofen:Eudragit E:HPMC combinations led to a more homogenous HPMC distribution within the systems than hot-melt extrusion, as revealed by mDSC and X-ray diffraction. This more homogenous HPMC distribution resulted in more pronounced hindrance for water and drug diffusion and, thus, slower drug release from spray-dried powder compared to hot-melt extrudates of identical composition. This "homogeneity/heterogeneity effect" even overcompensated the "system size effect": the surface exposed to the release medium was much larger in the case of the spray-dried powder. All formulations were stable during storage at ambient conditions in open vials.

  14. Differential modulation in binding of ketoprofen to bovine serum albumin in the presence and absence of surfactants: spectroscopic and calorimetric insights.

    Science.gov (United States)

    Misra, Pinaki P; Kishore, Nand

    2013-07-01

    Surfactants have long been implicated in the unique static and dynamic effect on the structure and function of serum albumins. However, there is very little information on the mode of interactions of drugs to serum albumins in presence of surfactants. The importance of such studies lay in the fact that apart from binding to serum albumins, surfactants are known to radically influence the solvents' micro environment and protein structure. Thus, we have studied the binding of the racemic form of ketoprofen with bovine serum albumin at pH 7.4 in the presence and absence of hexadecyl trimethyl ammonium bromide, sodium dodecyl sulfate, Triton X-100, and NaCl. The structural studies of ketoprofen with bovine serum albumin as investigated by circular dichroism spectroscopy revealed a significant stabilization of bovine serum albumin. However, the combined presence of the surfactants, NaCl and ketoprofen, demonstrated an extremely erratic behavior in terms of stabilization. Further the values of Stern-Volmer and dynamic quenching constant suggested the binding site of ketoprofen to be scattered in the region of domain I B and II A, close to Trp 134. The results of differential scanning calorimetry revealed that the binding of ketoprofen to bovine serum albumin leads to its temperature-dependent separation into two units. The binding parameters of bovine serum albumin obtained from isothermal titration calorimetry in the combined presence of ketoprofen and surfactants/NaCl correlate well with the differential scanning calorimetry studies further confirming the localization of ketoprofen in domain I B and II A. In the combined presence of surfactants, NaCl and ketoprofen, the binding of ketoprofen to bovine serum albumin exhibited altered binding parameters far different from the binding of ketoprofen alone. Overall, the experimental findings strongly indicated positive as well as negative modulation in the binding of ketoprofen to bovine serum albumin in the presence of

  15. Photodegradation kinetics and transformation products of ketoprofen, diclofenac and atenolol in pure water and treated wastewater.

    Science.gov (United States)

    Salgado, R; Pereira, V J; Carvalho, G; Soeiro, R; Gaffney, V; Almeida, C; Vale Cardoso, V; Ferreira, E; Benoliel, M J; Ternes, T A; Oehmen, A; Reis, M A M; Noronha, J P

    2013-01-15

    Pharmaceutical compounds such as ketoprofen, diclofenac and atenolol are frequently detected at relatively high concentrations in secondary effluents from wastewater treatment plants. Therefore, it is important to assess their transformation kinetics and intermediates in subsequent disinfection processes, such as direct ultraviolet (UV) irradiation. The photodegradation kinetics of these compounds using a medium pressure (MP) lamp was assessed in pure water, as well as in filtered and unfiltered treated wastewater. Ketoprofen had the highest time- and fluence-based rate constants in all experiments, whereas atenolol had the lowest values, which is consistent with the corresponding decadic molar absorption coefficient and quantum yield. The fluence-based rate constants of all compounds were evaluated in filtered and unfiltered wastewater matrices as well as in pure water. Furthermore, transformation products of ketoprofen, diclofenac and atenolol were identified and monitored throughout the irradiation experiments, and photodegradation pathways were proposed for each compound. This enabled the identification of persistent transformation products, which are potentially discharged from WWTP disinfection works employing UV photolysis.

  16. Greater allergenicity of topical ketoprofen in contact dermatitis confirmed by use.

    Science.gov (United States)

    Diaz, Ruth L; Gardeazabal, Jesus; Manrique, Pilar; Ratón, Juan A; Urrutia, Ignacio; Rodríguez-Sasiain, Jose M; Aguirre, Carmelo

    2006-05-01

    The use of topical non-steroidal anti-inflammatory drugs (NSAIDs) is very popular in spite of their doubtful efficacy and high number of generally not serious, but preventable, adverse effects, especially photoallergy. The allergenic potential of different topical NSAIDs was determined by performing a retrospective observational study of the period 1996-2001 and comparing the cases of allergy and photoallergy with the use of each topical NSAID. The diagnoses were obtained from a review of the clinical records of patch/photopatch testing carried out in the dermatology departments of 2 public hospitals in Bizkaia (Spain). The use of the different topical NSAIDs was obtained from invoices sent to the National Health System and the Reporting odds ratio (ROR) and Proportional reporting ratio (PRR) disproportionality estimates of the FEDRA database of the Spanish Pharmacovigilance System. A total of 139 contact reactions to topical NSAIDs were found with ketoprofen being responsible for 28% of the allergies and 82% of the contact photoallergies in spite of not being the most used topical NSAID (third in the ranking, diclofenac was the first). The ROR for ketoprofen was 3.9 (2.4-6.4) and the PRR 3.4 (2.1-5.5), thus confirming the possibility of a warning signal. The results support the need for regulatory action on topical ketoprofen.

  17. Anti-inflammatory pharmacotherapy with ketoprofen ameliorates experimental lymphatic vascular insufficiency in mice.

    Directory of Open Access Journals (Sweden)

    Kenta Nakamura

    Full Text Available BACKGROUND: Disruption of the lymphatic vasculature causes edema, inflammation, and end-tissue destruction. To assess the therapeutic efficacy of systemic anti-inflammatory therapy in this disease, we examined the impact of a nonsteroidal anti-inflammatory drug (NSAID, ketoprofen, and of a soluble TNF-alpha receptor (sTNF-R1 upon tumor necrosis factor (TNF-alpha activity in a mouse model of acquired lymphedema. METHODS AND FINDINGS: Lymphedema was induced by microsurgical ablation of major lymphatic conduits in the murine tail. Untreated control mice with lymphedema developed significant edema and extensive histopathological inflammation compared to sham surgical controls. Short-term ketoprofen treatment reduced tail edema and normalized the histopathology while paradoxically increasing TNF-alpha gene expression and cytokine levels. Conversely, sTNF-R1 treatment increased tail volume, exacerbated the histopathology, and decreased TNF-alpha gene expression. Expression of vascular endothelial growth factor-C (VEGF-C, which stimulates lymphangiogenesis, closely correlated with TNF-alpha expression. CONCLUSIONS: Ketoprofen therapy reduces experimental post-surgical lymphedema, yet direct TNF-alpha inhibition does not. Reducing inflammation while preserving TNF-alpha activity appears to optimize the repair response. It is possible that the observed favorable responses, at least in part, are mediated through enhanced VEGF-C signaling.

  18. Simultaneous HPLC determination of ketoprofen and its degradation products in the presence of preservatives in pharmaceuticals.

    Science.gov (United States)

    Dvorák, J; Hájková, R; Matysová, L; Nováková, L; Koupparis, M A; Solich, P

    2004-11-15

    A novel and quick high-performance liquid chromatography (HPLC) method with UV spectrophotometric detection was developed and validated for the determination of five compounds in topical gel. The described method is suitable for simultaneous determination of active component ketoprofen, two preservatives methylparaben and propylparaben and two degradation products of ketoprofen--3-acetylbenzophenone and 2-(3-carboxyphenyl) propionic acid--in a topical cream after long-term stability tests using ethylparaben as an internal standard. The chromatographic separation was performed on a 5microm Supelco Discovery C18 column (125mm x 4mm i.d., Sigma-Aldrich); the optimal mobile phase for separation of ketoprofen, methylparaben, propylparaben, degradation products 3-acetylbenzophenone and 2-(3-carboxyphenyl) propionic acid and ethylparaben as internal standard consists of a mixture of acetonitril, water and phosphate buffer pH 3.5 (40:58:2, v/v/v). At a flow rate of 1.0ml min(-1) and detection at 233nm, the total time of analysis was less than 10min. The method was applied for routine analysis (batch analysis and stability tests) of these compounds in topical pharmaceutical product.

  19. Ketoprofen combined with artery graft entubulization improves functional recovery of transected peripheral nerves.

    Science.gov (United States)

    Mohammadi, Rahim; Mehrtash, Moein; Nikonam, Nima; Mehrtash, Moied; Amini, Keyvan

    2014-12-01

    The objective was to assess the local effect of ketoprofen on sciatic nerve regeneration and functional recovery. Eighty healthy male white Wistar rats were randomized into four experimental groups of 20 animals each: In the transected group (TC), the left sciatic nerve was transected and nerve cut ends were fixed in the adjacent muscle. In the treatment group the defect was bridged using an artery graft (AG/Keto) filled with 10 microliter ketoprofen (0.1 mg/kg). In the artery graft group (AG), the graft was filled with phosphated-buffer saline alone. In the sham-operated group (SHAM), the sciatic nerve was exposed and manipulated. Each group was subdivided into four subgroups of five animals each and regenerated nerve fibres were studied at 4, 8, 12 and 16 weeks post operation. Behavioural testing, sciatic nerve functional study, gastrocnemius muscle mass and morphometric indices showed earlier regeneration of axons in AG/Keto than in AG group (p ketoprofen improved functional recovery and morphometric indices of the sciatic nerve. Local usage of this easily accessible therapeutic medicine is cost saving and avoids the problems associated with systemic administration.

  20. Design and In Vivo Anti-Inflammatory Effect of Ketoprofen Delayed Delivery Systems.

    Science.gov (United States)

    Cerciello, Andrea; Auriemma, Giulia; Morello, Silvana; Pinto, Aldo; Del Gaudio, Pasquale; Russo, Paola; Aquino, Rita P

    2015-10-01

    For the treatment of inflammatory-based diseases affected by circadian rhythms, the development of once-daily dosage forms is required to target early morning symptoms. In this study, Zn-alginate beads containing ketoprofen (K) were developed by a tandem technique prilling/ionotropic gelation. The effect of main critical variables on particles micromeritics, inner structure as well as on drug loading and in vitro drug release was studied. The in vivo anti-inflammatory efficacy was evaluated using a modified protocol of carrageenan-induced edema in rat paw administering beads to rats by oral gavage at 0, 3, or 5 h before edema induction. Good drug loading and desired particle size and morphology were obtained for the optimized formulation F20. In vitro dissolution studies showed that F20 had a gastroresistant behavior and delayed release of the drug in simulated intestinal fluid. The in vitro delayed release pattern was clearly reflected in the prolonged anti-inflammatory effect in vivo of F20, compared to pure ketoprofen; F20, administered 3 h before edema induction, showed a significant anti-inflammatory activity, reducing maximum paw volume in response to carrageenan injection, whereas no response was observed for ketoprofen. The designed beads appear a promising platform suitable for a delayed release of anti-inflammatory drugs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3451-3458, 2015.

  1. Accelerated ketoprofen release from spray-dried polymeric particles: importance of phase transitions and excipient distribution.

    Science.gov (United States)

    Gue, Emilie; Muschert, Susanne; Willart, Jean-Francois; Danede, Florence; Delcourt-Debruyne, Elisabeth; Descamps, Marc; Siepmann, Juergen

    2015-05-01

    HPMC-, PVPVA- and PVP-based microparticles loaded with 30% ketoprofen were prepared by spray drying suspensions or solutions in various water:ethanol blends. The inlet temperature, drying gas and feed flow rates were varied. The resulting differences in the ketoprofen release rates in 0.1 M HCl could be explained based on X-ray diffraction, mDSC, SEM and particle size analysis. Importantly, long term stable drug release could be provided, being much faster than: (i) drug release from a commercial reference product, (ii) the respective physical drug:polymer mixtures, as well as (iii) the dissolution of ketoprofen powder as received. In addition, highly supersaturated release media were obtained, which did not show any sign for re-crystallization during the observation period. Surprisingly, spraying suspensions resulted in larger microparticles exhibiting faster drug release compared to spraying solutions, which resulted in smaller particles exhibiting slower drug release. These effects could be explained based on the physico-chemical characteristics of the systems.

  2. Development of ketoprofen loaded proliposomal powders for improved gastric absorption and gastric tolerance: in vitro and in situ evaluation.

    Science.gov (United States)

    Gangishetty, Himabindu; Eedara, Basanth Babu; Bandari, Suresh

    2015-01-01

    The aim of the current investigation was to improve dissolution rate, gastric absorption and tolerance of a water insoluble non-steroidal anti-inflammatory drug ketoprofen by developing proliposomal powders. Ketoprofen proliposomal powders were prepared by solvent evaporation method with varying ratios of hydrogenated soyphosphatidyl choline (HSPC) and cholesterol. The prepared proliposomal powders were characterized for vesicle size, micromeritics, entrapment efficiency and in vitro dissolution behavior. Proliposomal powder (KPL3) composed of equimolar ratios of HSPC and cholesterol loaded on pearlitol SD 200 was selected as optimized formulation as it produced smaller liposomes (5.24 ± 1.35 μm) upon hydration with highest entrapment efficiency (53.16 ± 0.06%). All proliposomal powders showed improved dissolution characteristics than pure drug, however dissolution of drug from KPL3 was found to be highest (91.17 ± 6.3) and which is about 24 times higher than pure ketoprofen within 5 min. The transformation of crystalline ketoprofen to amorphous form was confirmed by solid state characterization. The absorption rate per hour for pure ketoprofen and proliposomal formulation (KPL3) was assessed in the stomach by conducting in situ gastric absorption studies in Wistar rats and was found to be 27 ± 1.22 and 36.98 ± 1.95%, respectively. In conclusion, enhanced dissolution and gastric absorption rate of ketoprofen from proliposomal powders suggest them as potential candidate for oral bioavailability improvement of ketoprofen.

  3. [Randomized, double-blind study with ketoprofen in gynecologic patients. Preemptive analgesia study following the Brevik-Stubhaug design].

    Science.gov (United States)

    Likar, R; Krumpholz, R; Pipam, W; Sadjak, A; Kapral, S; Forsthuber, E; Bernatzky, G; List, F W

    1998-04-01

    The clinical effect of ketoprofen is based not only on the inhibition of prostaglandin synthesis. Ketoprofen also acts through kynurenic acid as a central antagonist on the NMDA receptor. Due to this central analgesic mechanism of ketoprofen, we expected an analgesic preemptive effect. This study was carried out following the Breivik/Stubhaug preemptive effect study design. In 81 patients scheduled for gynaecological surgery a randomized double-blind study was performed. Three groups were studied: Group I received preoperative ketoprofen 100 mg i.v., 12 mg/h during surgery and for 48 hours afterwards. Group II received 100 mg ketoprofen as a bolus injection before the end of surgery, thereafter 12 mg/h ketoprofen continuously for 48 hours. Group III received a placebo during surgery and for 48 hours after surgery. The effects were measured postoperatively using a visual analog scale (VAS; at rest and on exertion) and the total analgesic consumption (PCA piritramide) within the first 48 hours after surgery. Furthermore, the time to first analgesic request was recorded. The vital signs and side effects were documented. The time to first analgesic request in group I was significantly longer than in groups II and III. In addition, the cumulative postoperative analgesic consumption during the first 24 hours after surgery was significantly lower in group I than in group III. Furthermore, the combination of an opioid with a non-opioid led to a lower pain score (VAS) at rest and on exertion. We showed a preemptive effect with ketoprofen, which was expressed significantly both in terms of the time to first analgesic request and by the lower analgesic consumption in the first 24 hours after surgery.

  4. Surrogate Analysis and Index Developer (SAID) tool

    Science.gov (United States)

    Domanski, Marian M.; Straub, Timothy D.; Landers, Mark N.

    2015-10-01

    The use of acoustic and other parameters as surrogates for suspended-sediment concentrations (SSC) in rivers has been successful in multiple applications across the Nation. Tools to process and evaluate the data are critical to advancing the operational use of surrogates along with the subsequent development of regression models from which real-time sediment concentrations can be made available to the public. Recent developments in both areas are having an immediate impact on surrogate research and on surrogate monitoring sites currently (2015) in operation.

  5. Effect of ketoprofen treatment on the uterine inflammatory response after AI of jennies with frozen semen.

    Science.gov (United States)

    Vilés, K; Rabanal, R; Rodríguez-Prado, M; Miró, J

    2013-04-15

    Artificial insemination (AI) involving the placing of frozen-thawed semen directly into the jenny uterine body is associated with very low pregnancy rates. This might be because of an exacerbation of the acute response of the endometrium to sperm, as seen in mares with persistent induced mating endometritis. Pregnancy rates can be increased in such mares, however, by including anti-inflammatory treatments in the insemination protocol (Bucca S, Carli A, Buckley T, Dolci G, Fogarty U. The use of dexamethasone administered to mares at breeding time in the modulation of persistent mating induced endometritis. Theriogenology 2008;70:1093-100; Rojer H, Aurich C. Treatment of persistent mating-induced endometritis in mares with the non-steroid anti-inflammatory drug vedaprofen. Reprod Domest Anim 2010;45:e458-60). To investigate the endometritis caused by the use of frozen-thawed semen in jennies, and to assess the response to ketoprofen treatment, endometrial cytological samples and biopsies from six healthy jennies were examined in a crossover design experiment. Samples were taken from jennies in estrus (E; control) and at 6 hours after AI with or without ketoprofen (+K and -K, respectively). Ketoprofen was administered iv 24 hours before and for 4 days after insemination (total = 2.2 mg/kg/24 hours for 5 days). All animals showed a severe inflammatory response to semen deposition. Polymorphonuclear neutrophil numbers in the cytological smears and biopsies differed significantly between the +K and E animals. No significant differences were recorded, however, between the +K and -K treatments. Eosinophils were observed in all sample types from all groups; these cells appear to be a feature of the normal jenny endometrium. Slight fibrosis was observed in some biopsies, but no significant relationship with inflammation was found. Intense cyclooxygenase-2 (COX-2) immunohistochemical labeling was detected in the -K biopsies. Less intense labeling was seen in those of the +K

  6. 酮洛芬药理研究进展%Progresses in Pharmacological Study of Ketoprofen

    Institute of Scientific and Technical Information of China (English)

    石开云; 余清宝

    2015-01-01

    Ketoprofen is a good 2-arylpropionic acid non-steroidal anti-inflammatory drug ( NSAID ) . It performs it's significant activi-ties on antipyretic, analgesic and anti-inflammatory by inhibiting the enzyme activities of cyclooxygenases ( COXs ) , proinflammatory pep-tides and/or lipoxygenases ( LOXs ) , further inhibiting the biosynthesis of those inflammatory substances such as prostaglandins ( PGs ) , bradykinins, leukotrienes ( LTs ) and thromboxanes ( TXs ) . The antiplatelet aggregation activity of ketoprofen quantitatively depends on the acidity. Its anti-inflammatory activity, which is strengthened by selectively inhibiting neutrophil chemotaxis induced by the interleukin-8 ( IL-8 ) , may be partly due to the abilities to scavenge reactive oxygen species ( ROS ) and reactive nitrogen species ( RNS ) , as well as the abilities to inhibit the respiratory burst of neutrophils triggered by various activating agents. Because of unselectively inhibiting COX-1 and COX-2, ketoprofen may prevent the biosynthesis of prostaglandin E2 ( PGE2 ) in gastric mucosal and further produce gastro-toxic activity, cause gastric mucosa damage or bleeding. Moreover, by inhibiting the COX-2 activity, ketoprofen reduce the concentration of endogenous PGF2α, and this may increase the potential risk of seizures. Local usage of ketoprofen may produce photosensitive toxic side effects caused by typeⅠfree radical reaction and contact dermatitis caused by the carboxyl group ( -COOH ) separated from the aromatic structure. In general, this paper systematically summarizes the progresses in pharmacological study of Ketoprofen, reveals its molecular mechanism of pharmacology, and illustrates the efficacy and side effects from its chemical structure nature. This paper may be helpful for the design and development of new products of ketoprofen class and the rational clinical use.%酮洛芬是2-芳基丙酸类非甾体抗炎药,主要通过抑制环氧合酶(COXs)、促炎肽和/或脂氧化

  7. Imaging Seeker Surrogate for IRCM evaluation

    NARCIS (Netherlands)

    Schleijpen, H.M.A.; Carpenter, S.R.; Mellier, B.; Dimmeler, A.

    2007-01-01

    NATO-SCI-139 and its predecessor groups have more than a decade of history in the evaluation and recommendation of EO and IR Countermeasures against anti-aircraft missiles. Surrogate Seekers have proven to be a valuable tool for this work. The use of surrogate seekers in international co-operations

  8. 77 FR 34788 - Surrogate Foreign Corporations

    Science.gov (United States)

    2012-06-12

    ... Internal Revenue Service 26 CFR Part 1 RIN 1545-BF47 Surrogate Foreign Corporations AGENCY: Internal... regulations regarding whether a foreign corporation is treated as a surrogate foreign corporation. The final ] regulations affect certain domestic corporations and partnerships (and certain parties related thereto),...

  9. Surrogate Guderley Test Problem Definition

    Energy Technology Data Exchange (ETDEWEB)

    Ramsey, Scott D. [Los Alamos National Laboratory; Shashkov, Mikhail J. [Los Alamos National Laboratory

    2012-07-06

    The surrogate Guderley problem (SGP) is a 'spherical shock tube' (or 'spherical driven implosion') designed to ease the notoriously subtle initialization of the true Guderley problem, while still maintaining a high degree of fidelity. In this problem (similar to the Guderley problem), an infinitely strong shock wave forms and converges in one-dimensional (1D) cylindrical or spherical symmetry through a polytropic gas with arbitrary adiabatic index {gamma}, uniform density {rho}{sub 0}, zero velocity, and negligible pre-shock pressure and specific internal energy (SIE). This shock proceeds to focus on the point or axis of symmetry at r = 0 (resulting in ostensibly infinite pressure, velocity, etc.) and reflect back out into the incoming perturbed gas.

  10. Use of Surrogate end points in HTA

    Directory of Open Access Journals (Sweden)

    Mangiapane, Sandra

    2009-08-01

    Full Text Available The different actors involved in health system decision-making and regulation have to deal with the question which are valid parameters to assess the health value of health technologies.So called surrogate endpoints represent in the best case preliminary steps in the casual chain leading to the relevant outcome (e. g. mortality, morbidity and are not usually directly perceptible by patients. Surrogate endpoints are not only used in trials of pharmaceuticals but also in studies of other technologies. Their use in the assessment of the benefit of a health technology is however problematic. In this report we intend to answer the following research questions: Which criteria need to be fulfilled for a surrogate parameter to be considered a valid endpoint? Which methods have been described in the literature for the assessment of the validity of surrogate endpoints? Which methodological recommendations concerning the use of surrogate endpoints have been made by international HTA agencies? Which place has been given to surrogate endpoints in international and German HTA reports? For this purpose, we choose three different approaches. Firstly, we conduct a review of the methodological literature dealing with the issue of surrogate endpoints and their validation. Secondly, we analyse current methodological guidelines of HTA agencies members of the International network of agencies for Health Technology Assessment (INAHTA as well as of agencies concerned with assessments for reimbursement purposes. Finally, we analyse the outcome parameter used in a sample of HTA reports available for the public. The analysis of methodological guidelines shows a very cautious position of HTA institutions regarding the use of surrogate endpoints in technology assessment. Surrogate endpoints have not been prominently used in HTA reports. None of the analysed reports based its conclusions solely on the results of surrogate endpoints. The analysis of German HTA reports shows a

  11. On Using Surrogates with Genetic Programming.

    Science.gov (United States)

    Hildebrandt, Torsten; Branke, Jürgen

    2015-01-01

    One way to accelerate evolutionary algorithms with expensive fitness evaluations is to combine them with surrogate models. Surrogate models are efficiently computable approximations of the fitness function, derived by means of statistical or machine learning techniques from samples of fully evaluated solutions. But these models usually require a numerical representation, and therefore cannot be used with the tree representation of genetic programming (GP). In this paper, we present a new way to use surrogate models with GP. Rather than using the genotype directly as input to the surrogate model, we propose using a phenotypic characterization. This phenotypic characterization can be computed efficiently and allows us to define approximate measures of equivalence and similarity. Using a stochastic, dynamic job shop scenario as an example of simulation-based GP with an expensive fitness evaluation, we show how these ideas can be used to construct surrogate models and improve the convergence speed and solution quality of GP.

  12. Crystallization Behavior and Relaxation Dynamics of Supercooled S‑Ketoprofen and the Racemic Mixture along an Isochrone

    DEFF Research Database (Denmark)

    Adrjanowicz, Karolina; Kaminski, Kamil; Paluch, Marian

    2015-01-01

    In this paper, we study crystallization behavior and molecular dynamics in the supercooled liquid state of the pharmaceutically important compound ketoprofen at various thermodynamic conditions. Dielectric relaxation for a racemic mixture was investigated in a wide range of temperatures and press......In this paper, we study crystallization behavior and molecular dynamics in the supercooled liquid state of the pharmaceutically important compound ketoprofen at various thermodynamic conditions. Dielectric relaxation for a racemic mixture was investigated in a wide range of temperatures...... of pure enantiomers and their 50–50 equimolar mixture in the metastable supercooled liquid state. Crystallization kinetic studies revealed that at the same isochronal conditions the behavior of the S-enantiomer and R,S-racemic mixture of ketoprofen is entirely different. This was examined in the context...

  13. Purification, crystallization and preliminary crystallographic analysis of Est25: a ketoprofen-specific hormone-sensitive lipase

    Energy Technology Data Exchange (ETDEWEB)

    Kim, SeungBum [Department of Biological and Molecular Engineering, College of Engineering, Ajou University, Suwon (Korea, Republic of); Joo, Sangbum [Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon (Korea, Republic of); Yoon, Hyun C.; Ryu, Yeonwoo [Department of Biological and Molecular Engineering, College of Engineering, Ajou University, Suwon (Korea, Republic of); Kim, Kyeong Kyu, E-mail: kkim@med.skku.ac.kr [Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon (Korea, Republic of); Kim, T. Doohun, E-mail: kkim@med.skku.ac.kr [Department of Biological and Molecular Engineering, College of Engineering, Ajou University, Suwon (Korea, Republic of)

    2007-07-01

    Est25, a ketoprofen-specific hormone-sensitive lipase from a metagenomic library, was crystallized and diffraction data were collected to 1.49 Å resolution. Ketoprofen, a nonsteroidal anti-inflammatory drug, inhibits the synthesis of prostaglandin. A novel hydrolase (Est25) with high ketoprofen specificity has previously been identified using a metagenomic library from environmental samples. Recombinant Est25 protein with a histidine tag at the N-terminus was expressed in Escherichia coli and purified in a homogenous form. Est25 was crystallized from 2.4 M sodium malonate pH 7.0 and X-ray diffraction data were collected to 1.49 Å using synchrotron radiation. The crystals belong to the monoclinic space group C2, with unit-cell parameters a = 197.8, b = 95.2, c = 99.4 Å, β = 97.1°.

  14. 以葡辛胺为拆分剂拆分酮基布洛芬%Resolving Ketoprofen Using n-Octyl-d-glucamine as an Optical Resolution Agent

    Institute of Scientific and Technical Information of China (English)

    朱圣东; 吴元欣; 喻子牛

    2005-01-01

    The process of resolution of racemic ketoprofen using n-octyl-d-glucamine as an optical resolution agent was investigated. The process consists of preparation of the diastereomer salt of ketoprofen with n-octyl-d-glucamine,liberation of S-(+)-ketoprofen from its diastereomer salt and recovery of the remaining ketoprofen and n-octyl-dglucamine. The suitable conditions for preparation of the diastereomer salt were methanol and ethyl acetate (1:1 by volume) as the solvent, the ratio of solvent volume to ketoprofen mass at 8 ml:1 g, and the molar ratio of ketoprofen to n-octyl-d-glucamine at 1:1. The preferred approach to liberate S-(+)-ketoprofen from its diastereomer salt was alkali dissolution, acid adjustment and ethyl acetate extraction. Racemization of the recovered ketoprofen could be achieved by reacting the recovered ketoprofen with 10% NaOH at 507 kPa for 6 h. The recovered n-octyl-dglucamine could be refined by acid dissolution and alkali adjustment. S-(+)-ketoprofen can be obtained with high optical purity and yield, showing that the present process is a practical and efficient one which can be used in industrial scale for preparation of S-(+)-ketoprofen.

  15. Differential pharmacokinetics and pharmacokinetic/pharmacodynamic modelling of robenacoxib and ketoprofen in a feline model of inflammation.

    Science.gov (United States)

    Pelligand, L; King, J N; Hormazabal, V; Toutain, P L; Elliott, J; Lees, P

    2014-08-01

    Robenacoxib and ketoprofen are acidic nonsteroidal anti-inflammatory drugs (NSAIDs). Both are licensed for once daily administration in the cat, despite having short blood half-lives. This study reports the pharmacokinetic/pharmacodynamic (PK/PD) modelling of each drug in a feline model of inflammation. Eight cats were enrolled in a randomized, controlled, three-period cross-over study. In each period, sterile inflammation was induced by the injection of carrageenan into a subcutaneously implanted tissue cage, immediately before the subcutaneous injection of robenacoxib (2 mg/kg), ketoprofen (2 mg/kg) or placebo. Blood samples were taken for the determination of drug and serum thromboxane (Tx)B2 concentrations (measuring COX-1 activity). Tissue cage exudate samples were obtained for drug and prostaglandin (PG)E2 concentrations (measuring COX-2 activity). Individual animal pharmacokinetic and pharmacodynamic parameters for COX-1 and COX-2 inhibition were generated by PK/PD modelling. S(+) ketoprofen clearance scaled by bioavailability (CL/F) was 0.114 L/kg/h (elimination half-life = 1.62 h). For robenacoxib, blood CL/F was 0.684 L/kg/h (elimination half-life = 1.13 h). Exudate elimination half-lives were 25.9 and 41.5 h for S(+) ketoprofen and robenacoxib, respectively. Both drugs reduced exudate PGE2 concentration significantly between 6 and 36 h. Ketoprofen significantly suppressed (>97%) serum TxB2 between 4 min and 24 h, whereas suppression was mild and transient with robenacoxib. In vivo IC50 COX-1/IC50 COX-2 ratios were 66.9:1 for robenacoxib and 1:107 for S(+) ketoprofen. The carboxylic acid nature of both drugs may contribute to the prolonged COX-2 inhibition in exudate, despite short half-lives in blood.

  16. Formulation development, in vitro and in vivo evaluation of microemulsion-based gel loaded with ketoprofen.

    Science.gov (United States)

    Nikumbh, Kishor V; Sevankar, Shailesh G; Patil, Moreshwar P

    2015-01-01

    Anti-inflammatory agents are widely used to relieve inflammation caused by various factors. This study was initiated with the intention to deliver low aqueous soluble ketoprofen to enhance its solubility by developing microemulsion system as a template and then incorporating it into gel phase. Initially ketoprofen was solubilized into microemulsion preparation made up of clove oil, Tween 20 and propylene glycol as oil phase, surfactant and co-surfactant respectively, then it was incorporated into different concentration of gelling phase using gelling agents namely Carbopol 940, Carbopol 934 and hydroxypropyl methyl cellulose K(4)M (HPMC K(4)M). Formulated emulgels were evaluated for their physical appearance, pH, rheological properties, globule size, extrudability, drug content, spreadability, bioadhesion strength, in vitro and ex vivo drug release, skin irritation test and anti-inflammatory activity. Microemulsion had shown globule size 396 nm, pH 6-6.7, viscosity 29.4 cps and zeta potential -12 mV indicating good stability. Formulated emulgels showed good physical appearance, skin acceptable pH 6-6.9, non-Newtonian shear thinning system, drug content 99.28 ± 0.16%, bioadhesion strength 48.4 gram force, globule size 473 nm, spreadability 22.96 gm.cm/s, good extrudability, in vitro release, ex vivo release did not showed any irritation reaction and possess a good anti-inflammatory activity. Selected batch showed enhanced drug release (92.42 ± 4.66%) as compared to marketed gel (65.94 ± 3.30). Similarly ex vivo release of formulation showed 72.22% release through mice skin compared with marketed gel. Formulations followed Korsmeyer-Peppas diffusion kinetic model. It was observed from the results that the formulated emulgel can provide promising delivery of ketoprofen.

  17. Design and evaluation of controlled onset extended release multiparticulate systems for chronotherapeutic delivery of ketoprofen

    Directory of Open Access Journals (Sweden)

    Shivakumar H

    2006-01-01

    Full Text Available An oral controlled onset extended release dosage form intended to approximate the chronobiology of rheumatoid arthritis is proposed for site-specific release to the colon. The multiparticulate system consisting of drug-loaded cellulose acetate cores encapsulated within Eudragit S-100 microcapsules was designed for chronotherapeutic delivery of ketoprofen. Drug-loaded cellulose acetate cores were prepared by emulsion solvent evaporation technique in an oily phase at different drug:polymer ratios (1:1, 2:1 and 4:1. These cores were successfully microencapsulated with Eudragit S-100 following the same technique at the core:coat ratio of 1:5. Scanning electron microscopy (SEM revealed that the cellulose acetate cores were discrete, uniform and spherical with a porous and rough surface, whereas the Eudragit microcapsules were discrete and spherical with a smooth and dense surface. In vitro drug release studies of the Eudragit microcapsules were performed in different pH conditions following pH-progression method for a period of 16 h. The release studies indicated that the microcapsules posses both pH-sensitive and controlled-release properties, showing limited drug release below pH 7.0 (6.40 to 8.94%, following which the cellulose acetate cores effectively controlled the drug release for a period of 11 h in pH 7.5. The differential scanning calorimetric and powder X-ray diffraction studies demonstrated that ketoprofen was present in dissolved state in the cellulose acetate polymeric matrix, which could explain the controlled drug release from the cores. The release of ketoprofen from Eudragit microcapsules in pH 7.5 depended on the cellulose acetate levels and was characterized by Higuchi′s diffusion model.

  18. Effects of post-partum administration of ketoprofen on sow health and piglet growth.

    Science.gov (United States)

    Viitasaari, Elina; Hänninen, Laura; Heinonen, Mari; Raekallio, Marja; Orro, Toomas; Peltoniemi, Olli; Valros, Anna

    2013-10-01

    The effect of the non-steroidal anti-inflammatory drug ketoprofen on the post farrowing phase of sows was studied in a randomized, blinded, placebo-controlled trial. Ketoprofen (3mg/kg) was administered intramuscularly to 20 healthy sows for 3 days post-partum (p.p.). The control group (n=20) received a saline placebo. Backfat, number of days of constipation and days before feed refusal were measured. Body condition (BCS) and shoulder sores were scored for 1 week p.p. Changes in BCS, backfat and shoulder sore scores were analysed with ANOVA. Blood was collected on days -1, 0, 5 and 14 with respect to medication. Aspartate aminotransferase (AST), creatinine kinase (CK), haptoglobin and serum amyloid A (SAA) were quantified and analysed with a Mann-Whitney U test. BCS and backfat decreased less following ketoprofen administration than with the placebo (-0.08 ± 0.2 vs. -0.8 ± 0.2, 1.0 ± 0.8mm vs. -2.0 ± 0.9 mm, respectively; Pketoprofen than placebo (Pketoprofen than placebo (5.5 ± 0.3 vs. 6.4 ± 0.3 days p.p.; Pketoprofen group than in the placebos (9.6 ± 0.9 vs. 3.8 ± 0.8 days p.p.; Pketoprofen administration than placebo on day 5 p.p. (Pketoprofen appeared to benefit sows during the first 2 weeks post farrowing, but caused some tissue irritation.

  19. Characteristics of chiral and racemic ketoprofen drugs using terahertz time-domain spectroscopy

    Science.gov (United States)

    Du, Yong; Liu, Jianjun; Hong, Zhi

    2013-08-01

    Absorption spectra of chiral S-(+)- and racemic RS-ketoprofen pharmaceutical molecules in crystalline form were recorded in the terahertz region between 6 and 66 cm-1 (0.2 ~ 2.0 THz) by using time-domain terahertz spectroscopic (THz-TDS) measurement. Different distinctive absorption features were observed which are strikingly sensitive to the change of subtle conformational structures within such isostructural crystal molecules. The results suggest that the THz-TDS technique can be definitely used for distinguishing between chiral and racemic compounds in pharmaceutical and biological fields.

  20. Ecotoxicity of ketoprofen, diclofenac, atenolol and their photolysis byproducts in zebrafish (Danio rerio).

    Science.gov (United States)

    Diniz, M S; Salgado, R; Pereira, V J; Carvalho, G; Oehmen, A; Reis, M A M; Noronha, J P

    2015-02-01

    The occurrence of pharmaceutical compounds in wastewater treatment plants and surface waters has been detected worldwide, constituting a potential risk for aquatic ecosystems. Adult zebrafish, of both sexes, were exposed to three common pharmaceutical compounds (atenolol, ketoprofen and diclofenac) and their UV photolysis by-products over seven days. The results show that diclofenac was removed to concentrationsketoprofen was reduced after the parent compounds were transformed by photolysis, whereas the toxicity increased significantly from the by-products generated through diclofenac photolysis. Therefore, diclofenac photolysis would possibly necessitate higher irradiation time to ensure that the associated by-products are completely degraded to harmless form(s).

  1. Acoustic and thermal anomalies in a liquid-glass transition of racemic S(+)-R(-) ketoprofen

    Science.gov (United States)

    Shibata, Tomohiko; Takayama, Haruki; Kim, Tae Hyun; Kojima, Seiji

    2014-01-01

    Acoustic and thermal properties of pharmaceutical racemic S(+)-R(-) ketoprofen were investigated in wide temperature range including glassy, supercooled liquid and liquid states by Brillouin scattering and temperature modulated DSC. Sound velocity and acoustic attenuation exhibited clear changes at 265 K indicating a liquid-glass transition and showed the typical structural relaxation above Tg. The high value of the fragility index m = 71 was determined by the dispersion of the complex heat capacity. New relaxation map was suggested in combination with previous study of dielectric measurement.

  2. Parents and children: "surrogate" paradigm of modernity.

    Science.gov (United States)

    Adam, Archimandrite; Akhaladze, Vakhtang

    2011-06-01

    The article provides an overview of surrogate motherhood--one of many currently available forms of Assisted Reproductive Technologies for couples who find themselves unable to conceive a child on their own. Within the years of its existence surrogate motherhood managed to accumulate lots of bioethical problems, paradoxes, dilemmas and collisions. Author represents some of them. Also the legal, moral and religious implications of surrogacy are addressed. The religious perspective from the Orthodox Christian, Catholic, Jewish, Hinduism, and Islamic points of view are provided. The author concludes that surrogate motherhood is not only the answer to childlessness but it supports metamorphosis of traditional attitude towards such human value as it is a family.

  3. Surrogate endpoints and emerging surrogate endpoints for risk reduction of cardiovascular disease.

    Science.gov (United States)

    Rasnake, Crystal M; Trumbo, Paula R; Heinonen, Therese M

    2008-02-01

    This article reviews surrogate endpoints and emerging biomarkers that were discussed at the annual "Cardiovascular Biomarkers and Surrogate Endpoints" symposium cosponsored by the US Food and Drug Administration (FDA) and the Montreal Heart Institute. The FDA's Center for Food Safety and Applied Nutrition (CFSAN) uses surrogate endpoints in its scientific review of a substance/disease relationship for a health claim. CFSAN currently recognizes three validated surrogate endpoints: blood pressure, blood total cholesterol, and blood low-density lipoprotein (LDL) concentration in its review of a health claim for cardiovascular disease (CVD). Numerous potential surrogate endpoints of CVD are being evaluated as the pathophysiology of heart disease is becoming better understood. However, these emerging biomarkers need to be validated as surrogate endpoints before they are used by CFSAN in the evaluation of a CVD health claim.

  4. Surrogate mothers: whose baby is it?

    Science.gov (United States)

    Cohen, B

    1984-01-01

    Advances in medical technology offer infertile couples who wish to raise children alternatives to adoption. The increasing number of surrogate mother contracts creates a myriad of legal issues surrounding the rights of the natural mother, the natural father and the child that is produced. In this Article, the Author discusses the legal issues and rights of the parties under the Constitution, the surrogate contract and family law principles. The Author proposes that courts should consider a surrogate contract as a revocable prebirth agreement which allows the natural mother to keep the child if she chooses. In addition, the Author advocates an interpretation of the statutes forbidding baby selling that would prohibit surrogate contracts in which the mother is paid a fee for the child.

  5. Neutron capture cross sections from Surrogate measurements

    Directory of Open Access Journals (Sweden)

    Scielzo N.D.

    2010-03-01

    Full Text Available The prospects for determining cross sections for compound-nuclear neutron-capture reactions from Surrogate measurements are investigated. Calculations as well as experimental results are presented that test the Weisskopf-Ewing approximation, which is employed in most analyses of Surrogate data. It is concluded that, in general, one has to go beyond this approximation in order to obtain (n,γ cross sections of sufficient accuracy for most astrophysical and nuclear-energy applications.

  6. Alternative methods to determine infectivity of Tulane virus: a surrogate for human norovirus

    Science.gov (United States)

    Culturable animal caliciviruses are widely-used as surrogates for human norovirus (HuNoV), which can not replicate in cells. The infectivity of a culturable virus was traditionally determined by plaque assay and/or 50% tissue culture infectious dose (TCID50) assay, both of which are time-consuming ...

  7. Spectroscopic, luminescence and in vitro biological studies of solid ketoprofen of heavier trivalent lanthanides and yttrium(III).

    Science.gov (United States)

    Gálico, D A; Lahoud, M G; Davolos, M R; Frem, R C G; Fraga-Silva, T F C; Venturini, J; Arruda, M S P; Bannach, G

    2014-11-01

    Solid-state compounds of the general formulae [ML3] (M=Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Y; L=ketoprofen) were synthesized and characterized using infrared, diffuse reflectance and luminescence spectroscopies. IR data suggested that the carboxylate group in ketoprofen is coordinated to the metals as a bidentate ligand. The triplet state energy level was determined using the Gd(3+) complex, which exhibited a ketoprofen blue luminescence when excited in the UV region. The compound containing Tb(3+) ion was sensitized by the ligand and emitted in the green region of the visible spectrum. On the other hand, for the analogous species containing the dysprosium ion, a competition for luminescence between the Dy(3+) and the ligand levels was observed. Finally, Tm(3+) complex exhibits only ligand luminescence. These optical behaviors are discussed based on rare earth energy diagrams. In addition, the compounds were evaluated for their anti-inflammatory activities. All the compounds showed a higher production of H2O2 and IL-10 than the ketoprofen, suggesting that the compounds exhibited an immunomodulatory effect and this opens up new perspectives for immunotherapeutic approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Systematically Optimized Ketoprofen-Loaded Novel Proniosomal Formulation for Periodontitis: In Vitro Characterization and In Vivo Pharmacodynamic Evaluation.

    Science.gov (United States)

    Yadav, N K; Nanda, Sanju; Sharma, Gajanand; Katare, O P

    2017-07-01

    Various preclinical/clinical studies support the effectiveness of ketoprofen in periodontitis; however, the literature reveals that novel delivery systems have been less explored for the drug in periodontitis. The current investigation aims to explore the potential of a pro-vesicular approach-based proniosomal drug delivery of ketoprofen for its effectiveness and validation in experimental periodontal disease (EPD). Formulations were developed using I-optimal mixture design. Developed formulations were characterized for entrapment efficiency, vesicle size, and in vitro drug release. Selected proniosomal gels were evaluated for mucoadhesiveness, ex vivo drug permeation, and retention studies. Optimized proniosomal gel was evaluated for surface morphology, rheological behavior, texture studies, and pharmacodynamic activity in EPD. The results showed that ketoprofen-loaded proniosomal formulations formed a mucoadhesive hydrogel comprising spherical and flexible vesicles. Viscosity and texture studies showed good adhesion and smoothness, which are desired for enhanced permeation. The disease condition was improved with preserved bone resorption process, that too with intact cementum vis-à-vis marketed gel formulation, when evaluated in the EPD model. The results lead to the conclusion that proniosomes can act as a promising carrier and can be effectively used for improved ketoprofen delivery in periodontal pockets.

  9. The characterization and dissolution performances of spray dried solid dispersion of ketoprofen in hydrophilic carriers

    Directory of Open Access Journals (Sweden)

    Siok-Yee Chan

    2015-10-01

    Full Text Available Solid dispersion is one of the most promising strategies to improve oral bioavailability of poorly soluble API. However, there are inconsistent dissolution performances of solid dispersion reported which entails further investigation. In this study, solid dispersions of ketoprofen in three hydrophilic carriers, i.e. PVP K30, PVPVA 6:4 and PVA were prepared and characterized. Physical characterization of the physical mixture of ketoprofen and carriers shows certain extent of amorphization of the API. This result is coinciding to evaluation of drug–polymer interaction using ATR-FTIR whereby higher amorphization was seen in samples with higher drug–polymer interaction. XRPD scanning confirms that fully amorphous solid dispersion was obtained for SD KTP PVP K30 and PVPVA system whereas partially crystalline system was obtained for SD KTP PVA. Interestingly, dissolution profiles of the solid dispersion had shown that degree of amorphization of KTP was not directly proportional to the dissolution rate enhancement of the solid dispersion system. Thus, it is concluded that complete amorphization does not guarantee dissolution enhancement of an amorphous solid dispersion system.

  10. A comparative study of ibuprofen and ketoprofen glass-forming liquids by molecular dynamics simulations

    Science.gov (United States)

    Ottou Abe, M. T.; Correia, N. T.; Ndjaka, J. M. B.; Affouard, F.

    2015-10-01

    In this paper, structural and dynamical properties of ibuprofen and ketoprofen glass-forming liquids have been investigated by means of molecular dynamics simulations. Molecular mobility of both materials is analyzed with respect to the different inter-molecular linear/cyclic hydrogen bonding associations. For ibuprofen, the dominant organization is found to be composed of small hydrogen bonding aggregates corresponding to cyclic dimers through the carboxyl group. For ketoprofen, the propensity of cyclic dimers is significantly reduced by the formation of hydrogen bonds with the ketone oxygen of the molecule altering the hydrogen bond (HB) associating structures that can be formed and thus molecular dynamics. The issue of the presence/absence of the peculiar low frequency Debye-type process in dielectric relaxation spectroscopy (DRS) data in these materials is addressed. Results obtained from simulations confirm that the Debye process originates from the internal cis-trans conversion of the —COOH carboxyl group. It is shown that the specific intermolecular HB structures associated to a given profen control the main dynamical features of this conversion, in particular its separation from the α-process, which make it detectable or not from DRS. For ibuprofen, the possible role of the —CCCO torsion motion, more "local" than the —COOH motion since it is less influenced by the intermolecular HBs, is suggested in the microscopic origin of the quite intense secondary γ-relaxation process detected from DRS.

  11. Gastroprotective effects of L-lysine salification of ketoprofen in ethanol-injured gastric mucosa.

    Science.gov (United States)

    Cimini, Annamaria; Brandolini, Laura; Gentile, Roberta; Cristiano, Loredana; Menghini, Paola; Fidoamore, Alessia; Antonosante, Andrea; Benedetti, Elisabetta; Giordano, Antonio; Allegretti, Marcello

    2015-04-01

    Ketoprofen L-lysine salt (KLS), a NSAID, is widely used for its analgesic efficacy and tolerability. L-lysine salification was reported to increase the solubility and the gastric absorption and tolerance of ketoprofen. Since the management of NSAIDs gastrotoxicity still represents a major limitation in prolonged therapies, mainly when gastric lesions are present, this study investigated the gastro-protective activity of L-lysine by using a well-established model of gastric mucosa injury, the ethanol-gastric injury model. Several evidences show that the damaging action of ethanol could be attributed to the increase of ROS, which plays a key role in the increase of lipid peroxidation products, including malonyldialdehyde and 4-hydroxy-2-nonenal. With the aim to unravel the mechanism of L-lysine gastroprotection, cellular MDA levels and 4-HNE protein adducts as markers of lipid peroxidation and a panel of key endogenous gastro-protective proteins were assayed. The data obtained indicate a gastroprotective effect of L-lysine on gastric mucosa integrity.

  12. Preparation and gamma scintigraphic evaluation of colon specific pellets of ketoprofen prepared by powder layering technology

    Directory of Open Access Journals (Sweden)

    M Subhabrota

    2011-03-01

    Full Text Available "n  "n Background and the purpose of the study:Multiparticulates by powder layering process have advantages of the uniform distribution of the binder solution, easy-to-clean pan and the possibility of applying the successive functional film coating using the same equipment. This study relates to a multiparticulate formulation comprising pellets with a multilayer of pectin-ethyl cellulose on non pareil seeds by powder layering technology. The pellets were prepared to target ketoprofen in colon based on the microbial enzyme dependent drug release mechanism. "nMethods: Multiparticulate formulation by powder layering technology was prepared by conventional pan coating process to evaluate the effect of 59% methoxylated pectin and 45 cps ethyl cellulose on coating label. The formulations were tagged with 99mTc-DTPA, a tracer in gamma scintigraphy study to evaluate the transit behavior of drug loaded pellets and compared with uncoated pellets to evaluate its specific release. "nResults: The transit behavior and scintigraphy image clearly indicates that the formulation can delay the drug release prior to colon. In albino rabbit, the coated pellets released drug in the colon indicating that site specificity has been achieved with pectin/ethyl cellulose coating at 1:2 ratio with 20% coating label. Major conclusion: Formulation containing pectin and ethyl cellulose with suitable coating label may be suitable as a coating formulation for colon delivery of ketoprofen and can be successfully evaluated by gamma scintigraphy method.

  13. Pharmacokinetics of ketoprofen in rabbit skin following topical application of lipid nanoparticles

    Science.gov (United States)

    Patel, Umesh

    The purpose of the thesis was to quantify ketoprofen (KTP) in rabbit skin following the topical application of lipid nanoparticles (Nanostructured lipid carriers, NLC). We tested two different types of formulations: one is (G') in which KTP is incorporated within the nanostructured lipid carriers (NLC) and the other is (H') which is a mixture of the nanostructured lipid carriers (NLC) and KTP dissolved in a vehicle (10% glycerol + 1% xanthan gum). Ketoprofen (KTP) is a non-steroidal anti-inflammatory drug administered systemically to treat arthritis. By conventional route severe side effects at the gastrointestinal level have been observed. Topical-application of lipid nanoparticles would be convenient alternative. The project is based on the (1) To study the calibration of microdialysis probes in both environment, in vivo as well as in vitro; (2) To compare two different type of formulation one is (G') with KTP incorporated within the nanostructured lipid carriers (NLC) and the other is (H') a mixture of the nanostructured lipid carriers (NLC) and KTP dissolved in a the vehicle (10% glycerol + 1% xanthan gum). The results of this study show a clear difference between the skin concentration profiles of the two formulations. Time to reach the maximum concentration is similar for both formulations. The formulation H', containing KTP is in external phase had higher Cmax (334ng/ml) than formulation G' containing KTP inside lipid particles (Cmax 32ng/ml).

  14. Preparation and characterization of ketoprofen-loaded solid lipid nanoparticles made from beeswax and carnauba wax.

    Science.gov (United States)

    Kheradmandnia, Soheila; Vasheghani-Farahani, Ebrahim; Nosrati, Mohsen; Atyabi, Fatemeh

    2010-12-01

    Solid lipid nanoparticles (SLNs) have been proposed as suitable colloidal carriers for delivery of drugs with limited solubility. Ketoprofen as a model drug was incorporated into SLNs prepared from a mixture of beeswax and carnauba wax using Tween 80 and egg lecithin as emulsifiers. The characteristics of the SLNs with various lipid and surfactant composition were investigated. The mean particle size of drug-loaded SLNs decreased upon mixing with Tween 80 and egg lecithin as well as upon increasing total surfactant concentration. SLNs of 75 ± 4 nm with a polydispersity index of 0.2 ± 0.02 were obtained using 1% (vol/vol) mixed surfactant at a ratio of 60:40 Tween 80 to egg lecithin. The zeta potential of these SLNs varied in the range of -15 to -17 (mV), suggesting the presence of similar interface properties. High drug entrapment efficiency of 97% revealed the ability of SLNs to incorporate a poorly water-soluble drug such as ketoprofen. Differential scanning calorimetry thermograms and high-performance liquid chromatographic analysis indicated the stability of nanoparticles with negligible drug leakage after 45 days of storage. It was also found that nanoparticles with more beeswax content in their core exhibited faster drug release as compared with those containing more carnauba wax in their structure.

  15. Crystal structure and characterization of esterase Est25 mutants reveal improved enantioselectivity toward (S)-ketoprofen ethyl ester.

    Science.gov (United States)

    Kim, Jinyeong; Seok, Seung-Hyeon; Hong, Eunsoo; Yoo, Tae Hyeon; Seo, Min-Duk; Ryu, Yeonwoo

    2017-03-01

    Esterases comprise a group of enzymes that catalyze the cleavage and synthesis of ester bonds. They are important in biotechnological applications owing to their enantioselectivity, regioselectivity, broad substrate specificity, and the fact that they do not require cofactors. In a previous study, we isolated the esterase Est25 from a metagenomic library. Est25 showed catalytic activity toward the (R,S)-ketoprofen ethyl ester but had low enantioselectivity toward the (S)-ketoprofen ethyl ester. Because (S)-ketoprofen has stronger anti-inflammatory effects and fewer side effects than (R)-ketoprofen, enantioselectivity of this esterase is important. In this study, we generated Est25 mutants with improved enantioselectivity toward the (S)-ketoprofen ethyl ester; improved enantioselectivity of mutants was established by analysis of their crystal structures. The enantioselectivity of mutants was influenced by substitution of Phe72 and Leu255. Substituting these residues changed the size of the binding pocket and the entrance hole that leads to the active site. The enantioselectivity of Est25 (E = 1.1 ± 0.0) was improved in the mutants F72G (E = 1.9 ± 0.2), L255W (E = 16.1 ± 1.1), and F72G/L255W (E = 60.1 ± 0.5). Finally, characterization of Est25 mutants was performed by determining the optimum reaction conditions, thermostability, effect of additives, and substrate specificity after substituting Phe72 and Leu255.

  16. Surrogates for herbicide removal in stormwater biofilters.

    Science.gov (United States)

    Zhang, Kefeng; Deletic, Ana; Page, Declan; McCarthy, David T

    2015-09-15

    Real time monitoring of suitable surrogate parameters are critical to the validation of any water treatment processes, and is of particularly high importance for validation of natural stormwater treatment systems. In this study, potential surrogates for herbicide removal in stormwater biofilters (also known as stormwater bio-retention or rain-gardens) were assessed using field challenge tests and matched laboratory column experiments. Differential UV absorbance at 254mn (ΔUVA254), total phosphorus (ΔTP), dissolved phosphorus (ΔDP), total nitrogen (ΔTN), ammonia (ΔNH3), nitrate and nitrite (ΔNO3+NO2), dissolved organic carbon (ΔDOC) and total suspended solids (ΔTSS) were compared with glyphosate, atrazine, simazine and prometryn removal rates. The influence of different challenge conditions on the performance of each surrogate was studied. Differential TP was significantly and linearly related to glyphosate reduction (R(2) = 0.75-0.98, P herbicides were reliable under normal and challenge dry conditions, but weaker correlations were observed under challenge wet conditions. Of those tested, ΔTP is the most promising surrogate for glyphosate removal and ΔUVA254 is a suitable surrogate for triazines removal in stormwater biofilters. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. HPLC method with solid-phase extraction for determination of (R)- and (S)-ketoprofen in plasma without caffeine interference: application to pharmacokinetic studies in rats.

    Science.gov (United States)

    López-Muñoz, Francisco Javier; Vara Gama, Nancy; Soria-Arteche, Olivia; Hurtado y de la Peña, Marcela; Domínguez-Ramírez, Adriana Miriam; Medina López, José Raúl

    2014-01-01

    A fast and reproducible high-performance liquid chromatography method has been developed for the determination of (R)- and (S)-ketoprofen. Ketoprofen enantiomers were determined in plasma samples (50 µL), after solid-phase extraction, using diclofenac as internal standard. Analyses were performed on a (S, S)-Whelk-O 1 stainless steel column (5 µm, 250 × 4.6 mm) using hexane-ethanol-acetic acid (93:7:0.5, v/v/v) as the mobile phase and detection at 254 nm. The method was selective for ketoprofen enantiomers in the presence of caffeine and endogenous plasma compounds. Standard curves were linear (R(2) > 0.999) over the concentration range of 0.25-12.50 and 0.25 µg/mL was taken as the limit of quantification. The intra- and interday precision (relative standard deviation) values were 0.05). The validated method was successfully applied in determination of (S)-ketoprofen in Wistar rats after oral administration of 3.2 mg/kg of (S)-ketoprofen alone or 3.2 mg/kg of (S)-ketoprofen + 17.8 mg/kg of caffeine.

  18. Preparation of ketoprofen ethosomal gels%酮洛芬醇质体凝胶的研制

    Institute of Scientific and Technical Information of China (English)

    王军; 何文; 罗丽萍

    2012-01-01

    Objective To prepare ketoprofen ethosomal gels and study the quality preliminarily. Methods The ketoprofen ethosomes were prepared by injection method. The optimal formulation and preparation were screened by orthogonal experiments. The ethosomal gels were prepared by mixing method. The content of ketoprofen was determined by HPLC and the entrapment efficiency of the ethosomes was measured by dialysis method. Results The shape of the ketoprofen ethosomes was spherical with homogeneous size and the average value of mean particle size was(185.8 ±58.2)nm. The average encapsulation efficiency was (72.6 ±3.2)%. The linear range of ketoprofen was 1.5-12.0 μg · mL-1(r=0.999 9). The average recovery of ketoprofen is (99.3 ±1. 5)%. Conclusion The preparation is simple and reasonable with promising repeatability and controllable quality.%目的 研制酮洛芬醇质体凝胶,并对其质量进行初步考察.方法 采用注入法制备酮洛芬醇质体,通过正交实验优选较佳处方和工艺;采用研和法制备醇质体凝胶,HPLC测定其中主药的含量,透析法测定包封率.结果 酮洛芬醇质体形态圆整,粒径均匀,平均粒径为(185.8±58.2)nm,平均包封率为(72.6±3.2)%.酮洛芬线性浓度范围为1.5-12.0μg·mL-1(r=0.9999),平均回收率为(99.3±1.5)%.结论 本制剂制备工艺简单可行,重现性好,质量稳定可控.

  19. Modified coaxial electrospinning for the preparation of high-quality ketoprofen-loaded cellulose acetate nanofibers.

    Science.gov (United States)

    Yu, Deng-Guang; Yu, Jia-Hui; Chen, Lan; Williams, Gareth R; Wang, Xia

    2012-10-01

    This study investigates the use of a modified coaxial electrospinning process in the production of drug-loaded cellulose acetate (CA) nanofibers. With CA employed as a filament-forming matrix and ketoprofen (KET) as an active pharmaceutical ingredient, modified coaxial processes using sheath fluids comprising only mixed solvents were undertaken. With a sheath-to-core flow rate ratio of 0.2:1, the nanofibers prepared from the coaxial process had a smaller average diameter, narrower size distribution, more uniform structures, and smoother surface morphologies than those generated from single fluid electrospinning. In addition, the coaxial fibers provided a better zero-order drug release profile. The use of a sheath solvent means that the core jet is subjected to electrical drawing for a longer period, facilitating homogeneous core jet solidification and retarding the formation of wrinkles on the surface of the nanofibers. This modified coaxial electrospinning protocol allows the systematic fabrication of functional polymer nanofibers with improved quality.

  20. Preparation and characterization of ketoprofen loaded eudragit RS polymeric nanoparticles for controlled release

    Science.gov (United States)

    Anh, Nguyen Tuan; Chi, Nguyen T.; Khai Tran, T.; Tuyen Dao, T. P.; Nhan Le, N. T.; Mau Chien, Dang; Hoai, Nguyen To

    2012-12-01

    Nanospheres containing ketoprofen (Keto) and polymer eudragit RS were prepared using an emulsion solvent evaporation method. The ultrasonic probe (VCX500, vibracell) was used as a tool to disperse oil phase into aqueous phase leading to water/oil emulsion. Nanoparticles were successfully prepared and their morphologies and diameters were confirmed by transmission electron microscope (TEM) and dynamic light scattering (DLS), respectively. The result showed that particles were spherical with submicron size. The particle size was dependent on the RS concentration, emulsification tools and the types of organic solvents. For the encapsulation ability, Keto-loaded RS nanoparticle showed 9.8% of Keto in nanoparticle, which was evaluated by high-performance liquid chromatography (HPLC). Moreover, the drug release behavior of Keto-loaded eudragit RS nanoparticle was also investigated in vitro at pH 7.4 and compared to referential profenid.

  1. Ketoprofen impairs immunosuppression induced by severe sepsis and reveals an important role for prostaglandin E2.

    Science.gov (United States)

    Brogliato, Ariane Rennó; Antunes, Carlos A; Carvalho, Renato S; Monteiro, Ana Paula T; Tinoco, Rodrigo F; Bozza, Marcelo T; Canetti, Claudio; Peters-Golden, Marc; Kunkel, Steven L; Vianna-Jorge, Rosane; Benjamim, Claudia Farias

    2012-12-01

    The mechanism of immunosuppression induced by severe sepsis is not fully understood. The production of prostaglandin E2 (PGE2) during sepsis is well known, but its role in long-term consequences of sepsis has not been explored. The current study evaluates the role of PGE2 in the development of immunosuppression secondary to sepsis and its potential as therapeutic target. Cecal ligation and puncture was used as an experimental model for sepsis induction in Balb/c and C57BL/6 mice. Immunosuppression was evaluated by the response to secondary infection with Aspergillus fumigatus in sepsis survivors. The role of prostanoids was evaluated in vivo and in vitro by treatment with the cyclooxygenase inhibitor ketoprofen. Balb/c mice were more susceptible than C57BL/6 to severe sepsis and to secondary infection, with a greater mortality rate. Prostaglandin E2 concentrations found in bronchoalveolar lavage in sham and cecal ligation and puncture group after fungal challenge were much higher in Balb/c than in C57BL/6 mice. Ketoprofen treatment improved survival of septic Balb/c mice subjected to secondary infection, while also enhancing macrophage phagocytosis and neutrophil recruitment to the lungs. We identified a pivotal role for PGE2 acting on EP4 receptors in modulating cytokine production differentially by sham and septic macrophages. Furthermore, sepsis also altered key enzymes in PGE2 synthesis and degradation. Our results indicate the involvement of PGE2 in severe sepsis-induced immunosuppression. Inhibition of PGE2 production represents an attractive target to improve innate immune response against secondary infection in the immunocompromised host.

  2. Nitrate Salt Surrogate Blending Scoping Test Plan

    Energy Technology Data Exchange (ETDEWEB)

    Anast, Kurt Roy [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-11-13

    Test blending equipment identified in the “Engineering Options Assessment Report: Nitrate Salt Waste Stream Processing”. Determine if the equipment will provide adequate mixing of zeolite and surrogate salt/Swheat stream; optimize equipment type and operational sequencing; impact of baffles and inserts on mixing performance; and means of validating mixing performance

  3. Videotrees: Improving video surrogate presentation using hierarchy

    NARCIS (Netherlands)

    Jansen, Michel; Heeren, Willemijn; Dijk, van Betsy

    2008-01-01

    As the amount of available video content increases, so does the need for better ways of browsing all this material. Because the nature of video makes it hard to process, the need arises for adequate surrogates for video that can readily be skimmed and browsed. In this paper, the effects of the use o

  4. Glass transition dynamics of anti-inflammatory ketoprofen studied by Raman scattering and terahertz time-domain spectroscopy

    Science.gov (United States)

    Shibata, Tomohiko; Igawa, Hikaru; Kim, Tae Hyun; Mori, Tatsuya; Kojima, Seiji

    2014-03-01

    A liquid-glass transition and a crystalline state of pharmaceutical racemic ketoprofen were studied by Raman scattering and the broadband terahertz time-domain spectroscopy (THz-TDS) in the frequency range from 9 to 260 cm-1. The low-frequency Raman scattering spectra clearly shows the remarkable change related to a liquid-glass transition at about Tg = 267 K. After melt-quenching at liquid nitrogen temperature, a boson peak appears at about 16.5 cm-1 near and below Tg and the intensity of quasi-elastic scattering related to structural relaxation increases markedly on heating. The crystalline racemic ketoprofen of "conformer A" shows the noncoincidence effect of mode frequencies below 200 cm-1 between Raman scattering spectra and dielectric spectra observed by THz-TDS.

  5. Characterization of a poly(ether urethane)-based controlled release membrane system for delivery of ketoprofen

    Science.gov (United States)

    Macocinschi, Doina; Filip, Daniela; Vlad, Stelian; Oprea, Ana Maria; Gafitanu, Carmen Anatolia

    2012-10-01

    A poly(ether urethane) based on polytetrahydrofuran containing hydroxypropyl cellulose for biomedical applications was tested for its biocompatibility. Ketoprofen was incorporated (3% and 6%) in the polyurethane matrix as an anti-inflammatory drug. Kinetic and drug release mechanisms were studied. The pore size and pore size distribution of the polyurethane membranes were investigated by scanning electron microscopy. Surface tension characteristics as well as moisture sorption properties such as diffusion coefficients and equilibrium moisture contents of the membrane material were studied. It was found that kinetics and release mechanisms are in function of medium pH, composition of polymer-drug system, pore morphology and pore size distribution. Prolonged nature of release of ketoprofen is assured by low amount of drug in polyurethane membrane and physiological pH.

  6. Combustion Kinetic Studies of Gasolines and Surrogates

    KAUST Repository

    Javed, Tamour

    2016-11-01

    Future thrusts for gasoline engine development can be broadly summarized into two categories: (i) efficiency improvements in conventional spark ignition engines, and (ii) development of advance compression ignition (ACI) concepts. Efficiency improvements in conventional spark ignition engines requires downsizing (and turbocharging) which may be achieved by using high octane gasolines, whereas, low octane gasolines fuels are anticipated for ACI concepts. The current work provides the essential combustion kinetic data, targeting both thrusts, that is needed to develop high fidelity gasoline surrogate mechanisms and surrogate complexity guidelines. Ignition delay times of a wide range of certified gasolines and surrogates are reported here. These measurements were performed in shock tubes and rapid compression machines over a wide range of experimental conditions (650 – 1250 K, 10 – 40 bar) relevant to internal combustion engines. Using the measured the data and chemical kinetic analyses, the surrogate complexity requirements for these gasolines in homogeneous environments are specified. For the discussions presented here, gasolines are classified into three categories: (i)\\tLow octane gasolines including Saudi Aramco’s light naphtha fuel (anti-knock index, AKI = (RON + MON)/2 = 64; Sensitivity (S) = RON – MON = 1), certified FACE (Fuels for Advanced Combustion Engines) gasoline I and J (AKI ~ 70, S = 0.7 and 3 respectively), and their Primary Reference Fuels (PRF, mixtures of n-heptane and iso-octane) and multi-component surrogates. (ii)\\t Mid octane gasolines including FACE A and C (AKI ~ 84, S ~ 0 and 1 respectively) and their PRF surrogates. Laser absorption measurements of intermediate and product species formed during gasoline/surrogate oxidation are also reported. (iii)\\t A wide range of n-heptane/iso-octane/toluene (TPRF) blends to adequately represent the octane and sensitivity requirements of high octane gasolines including FACE gasoline F and G

  7. A novel surrogate index for hepatic insulin resistance.

    LENUS (Irish Health Repository)

    Vangipurapu, J

    2011-03-01

    In epidemiological and genetic studies surrogate indices are needed to investigate insulin resistance in different insulin-sensitive tissues. Our objective was to develop a surrogate index for hepatic insulin resistance.

  8. Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs.

    Science.gov (United States)

    Luna, Stelio P L; Basílio, Ana C; Steagall, Paulo V M; Machado, Luciana P; Moutinho, Flávia Q; Takahira, Regina K; Brandão, Cláudia V S

    2007-03-01

    To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. 36 adult dogs. Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. For serum gamma-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.

  9. Elucidation of the mechanism of inhibition of cyclooxygenases by acyl-coenzyme A and acylglucuronic conjugates of ketoprofen.

    Science.gov (United States)

    Levoin, Nicolas; Blondeau, Céline; Guillaume, Cécile; Grandcolas, Line; Chretien, Françoise; Jouzeau, Jean-Yves; Benoit, Etienne; Chapleur, Yves; Netter, Patrick; Lapicque, Françoise

    2004-11-15

    Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the cyclooxygenase (COX) isoforms which accounts for their clinical effects. The differential inhibition of COX-1 and COX-2 is not sufficient to explain the absence of a correlation between in vitro and in vivo effects, especially for 2-aryl-propionates, thus indicating the participation of metabolites. Conjugates to glucuronic acid and to coenzyme-A are mainly produced, and have been shown to be chemically reactive. Therefore, we studied the interaction of the ketoprofen metabolites with the COX enzymes. After incubation with bovine pulmonary artery endothelial cells (BPAEC), COX-1 was inhibited stereoselectively by S-ketoprofen acylglucuronide, and more significantly by CoA-thioester. After washing-out the medium, COX-1 activity was essentially recovered, indicating a reversible inhibition. In LPS-stimulated J774.2 cells, COX activity (mainly inducible COX-2) was inhibited reversibly and stereospecifically by S-ketoprofen glucuronide, whereas it disappeared totally and was not recovered after incubation with CoA-thioester. Correspondingly, inhibition of purified COX-2 with this compound was observed to be rapid and irreversible. Using an anti-ketoprofen antibody, COX immunoprecipitated from cells exhibited adduct formation for COX-2 but not for COX-1. This was observed after incubation with CoA-thioester, and, surprisingly, also with glucuronide. Molecular docking gave support to explain this discrepancy: the glucuronide was found to establish a strong interaction with Y115 located in the membrane binding domain, whereas the thioester was preferentially bound to the active site of the enzyme. Overall, our results suggest a contribution of CoA-thioester metabolites of carboxylic NSAIDs to their pharmacological action by irreversibly and selectively inhibiting COX-2.

  10. Evaluation of the stability of ketoprofen in pluronic lecithin organogel and the determination of an appropriate beyond-use date.

    Science.gov (United States)

    Peacock, Gina F; Sauvageot, Jurgita; Addo, Richard T

    2014-01-01

    Previous reports indicate that pharmacists are assigning a wide variety of beyond-use dates to extemporaneously compounded medications in topical Pluronic lecithin organogel. The objective of this study was to evaluate the stability of ketoprofen in Pluronic lecithin organogel over a period of six months and to determine an appropriate beyond-use date for this formulation. A stability-indicating high-performance liquid chromatography method for ketoprofen in Pluronic lecithin organogel was validated in our laboratory. Samples of the formulation were analyzed by high-performance liquid chromatography at 0, 7, 14, 21, 28, 45, 60, 90, and 180 days. At each time point, the average concentration and average percent of initial concentration were calculated. The beyond-use date was determined as the time period that the samples were physically stable and maintained at least 90% of the initial concentration. Ketoprofen in Pluronic lecithin organogel was chemically and physically stable for six months when stored at room temperature and protected from light. Therefore, a beyond-use date of six months is appropriate for this preparation.

  11. Characterization of a poly(ether urethane)-based controlled release membrane system for delivery of ketoprofen

    Energy Technology Data Exchange (ETDEWEB)

    Macocinschi, Doina, E-mail: eradro2002@yahoo.com [Department of Physical Chemistry of Polymers, ' Petru Poni' Institute of Macromolecular Chemistry, Aleea Gr. Ghica Voda 41 A, 700487 Iasi (Romania); Filip, Daniela; Vlad, Stelian; Oprea, Ana Maria [Department of Physical Chemistry of Polymers, ' Petru Poni' Institute of Macromolecular Chemistry, Aleea Gr. Ghica Voda 41 A, 700487 Iasi (Romania); Gafitanu, Carmen Anatolia [Faculty of Pharmacy, ' Gr. T. Popa' University of Medicine and Pharmacy, Universitatii 16, 700115 Iasi (Romania)

    2012-10-15

    Highlights: Black-Right-Pointing-Pointer Ketoprofen incorporation in poly(ether urethane) microporous membrane. Black-Right-Pointing-Pointer Moisture sorption properties of as-cast membrane. Black-Right-Pointing-Pointer Drug release mechanisms in function of pH and composition of membranes. - Abstract: A poly(ether urethane) based on polytetrahydrofuran containing hydroxypropyl cellulose for biomedical applications was tested for its biocompatibility. Ketoprofen was incorporated (3% and 6%) in the polyurethane matrix as an anti-inflammatory drug. Kinetic and drug release mechanisms were studied. The pore size and pore size distribution of the polyurethane membranes were investigated by scanning electron microscopy. Surface tension characteristics as well as moisture sorption properties such as diffusion coefficients and equilibrium moisture contents of the membrane material were studied. It was found that kinetics and release mechanisms are in function of medium pH, composition of polymer-drug system, pore morphology and pore size distribution. Prolonged nature of release of ketoprofen is assured by low amount of drug in polyurethane membrane and physiological pH.

  12. A qualitative investigation of selecting surrogate decision-makers

    NARCIS (Netherlands)

    Edwards, S.J.L.; Brown, P.; Twyman, M.A.; Christie, D.; Rakow, T.

    2011-01-01

    Background Empirical studies of surrogate decision-making tend to assume that surrogates should make only a 'substituted judgement'—that is, judge what the patient would want if they were mentally competent. Objectives To explore what people want in a surrogate decision-maker whom they themselves se

  13. System Reliability Analysis Capability and Surrogate Model Application in RAVEN

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian; Alfonsi, Andrea; Huang, Dongli; Gleicher, Frederick; Wang, Bei; Adbel-Khalik, Hany S.; Pascucci, Valerio; Smith, Curtis L.

    2015-11-01

    This report collect the effort performed to improve the reliability analysis capabilities of the RAVEN code and explore new opportunity in the usage of surrogate model by extending the current RAVEN capabilities to multi physics surrogate models and construction of surrogate models for high dimensionality fields.

  14. Revisiting photodynamic therapy dosimetry: reductionist & surrogate approaches to facilitate clinical success

    Science.gov (United States)

    Pogue, Brian W.; Elliott, Jonathan T.; Kanick, Stephen C.; Davis, Scott C.; Samkoe, Kimberley S.; Maytin, Edward V.; Pereira, Stephen P.; Hasan, Tayyaba

    2016-04-01

    Photodynamic therapy (PDT) can be a highly complex treatment, with many parameters influencing treatment efficacy. The extent to which dosimetry is used to monitor and standardize treatment delivery varies widely, ranging from measurement of a single surrogate marker to comprehensive approaches that aim to measure or estimate as many relevant parameters as possible. Today, most clinical PDT treatments are still administered with little more than application of a prescribed drug dose and timed light delivery, and thus the role of patient-specific dosimetry has not reached widespread clinical adoption. This disconnect is at least partly due to the inherent conflict between the need to measure and understand multiple parameters in vivo in order to optimize treatment, and the need for expedience in the clinic and in the regulatory and commercialization process. Thus, a methodical approach to selecting primary dosimetry metrics is required at each stage of translation of a treatment procedure, moving from complex measurements to understand PDT mechanisms in pre-clinical and early phase I trials, towards the identification and application of essential dose-limiting and/or surrogate measurements in phase II/III trials. If successful, identifying the essential and/or reliable surrogate dosimetry measurements should help facilitate increased adoption of clinical PDT. In this paper, examples of essential dosimetry points and surrogate dosimetry tools that may be implemented in phase II/III trials are discussed. For example, the treatment efficacy as limited by light penetration in interstitial PDT may be predicted by the amount of contrast uptake in CT, and so this could be utilized as a surrogate dosimetry measurement to prescribe light doses based upon pre-treatment contrast. Success of clinical ALA-based skin lesion treatment is predicted almost uniquely by the explicit or implicit measurements of photosensitizer and photobleaching, yet the individualization of treatment

  15. Revisiting photodynamic therapy dosimetry: reductionist & surrogate approaches to facilitate clinical success.

    Science.gov (United States)

    Pogue, Brian W; Elliott, Jonathan T; Kanick, Stephen C; Davis, Scott C; Samkoe, Kimberley S; Maytin, Edward V; Pereira, Stephen P; Hasan, Tayyaba

    2016-04-01

    Photodynamic therapy (PDT) can be a highly complex treatment, with many parameters influencing treatment efficacy. The extent to which dosimetry is used to monitor and standardize treatment delivery varies widely, ranging from measurement of a single surrogate marker to comprehensive approaches that aim to measure or estimate as many relevant parameters as possible. Today, most clinical PDT treatments are still administered with little more than application of a prescribed drug dose and timed light delivery, and thus the role of patient-specific dosimetry has not reached widespread clinical adoption. This disconnect is at least partly due to the inherent conflict between the need to measure and understand multiple parameters in vivo in order to optimize treatment, and the need for expedience in the clinic and in the regulatory and commercialization process. Thus, a methodical approach to selecting primary dosimetry metrics is required at each stage of translation of a treatment procedure, moving from complex measurements to understand PDT mechanisms in pre-clinical and early phase I trials, towards the identification and application of essential dose-limiting and/or surrogate measurements in phase II/III trials. If successful, identifying the essential and/or reliable surrogate dosimetry measurements should help facilitate increased adoption of clinical PDT. In this paper, examples of essential dosimetry points and surrogate dosimetry tools that may be implemented in phase II/III trials are discussed. For example, the treatment efficacy as limited by light penetration in interstitial PDT may be predicted by the amount of contrast uptake in CT, and so this could be utilized as a surrogate dosimetry measurement to prescribe light doses based upon pre-treatment contrast. Success of clinical ALA-based skin lesion treatment is predicted almost uniquely by the explicit or implicit measurements of photosensitizer and photobleaching, yet the individualization of treatment

  16. A Technical Approach to Expedited Processing of NTPR Radiation Dose Assessments

    Science.gov (United States)

    2011-10-01

    Dose Cohort .............................................................................. 87 B-2 Treatment of Exclusions...magnitude given the same scenario of exposure. • Uniformity in the treatment of upper-bound doses is maintained. • Approved NTPR standard methods...Pharynx (140-149) TONSILS TONSILS Tonsils ET Region+ Surrogate Oral Cavity and Pharynx (140-149) TRACHEA TRACHEA Trachea Lung Surrogate Lung (162

  17. Surrogate decision making and intellectual virtue.

    Science.gov (United States)

    Bock, Gregory L

    2014-01-01

    Patients can be harmed by a religiously motivated surrogate decision maker whose decisions are contrary to the standard of care; therefore, surrogate decision making should be held to a high standard. Stewart Eskew and Christopher Meyers proposed a two-part rule for deciding which religiously based decisions to honor: (1) a secular reason condition and (2) a rationality condition. The second condition is based on a coherence theory of rationality, which they claim is accessible, generous, and culturally sensitive. In this article, I will propose strengthening the rationality condition by grounding it in a theory of intellectual virtue, which is both rigorous and culturally sensitive. Copyright 2014 The Journal of Clinical Ethics. All rights reserved.

  18. DJ-1 plays an important role in caffeic acid-mediated protection of the gastrointestinal mucosa against ketoprofen-induced oxidative damage.

    Science.gov (United States)

    Cheng, Yu-Ting; Ho, Cheng-Ying; Jhang, Jhih-Jia; Lu, Chi-Cheng; Yen, Gow-Chin

    2014-10-01

    Ketoprofen is widely used to alleviate pain and inflammation in clinical medicine; however, this drug may cause oxidative stress and lead to gastrointestinal (GI) ulcers. We previously reported that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in protecting cells against reactive oxygen species, and it facilitates the prevention of ketoprofen-induced GI mucosal ulcers. Recent reports suggested that Nrf2 becomes unstable in the absence of DJ-1/PARK7, attenuating the activity of Nrf2-regulated downstream antioxidant enzymes. Thus, increasing Nrf2 translocation by DJ-1 may represent a novel means for GI protection. In vitro, caffeic acid increases the nuclear/cytosolic Nrf2 ratio and the mRNA expression of the downstream antioxidant enzymes, ϒ-glutamyl cysteine synthetase, glutathione peroxidase, glutathione reductase, and heme oxygenase-1, by activating the JNK/p38 pathway in Int-407 cells. Moreover, knockdown of DJ-1 also reversed caffeic acid-induced nuclear Nrf2 protein expression in a JNK/p38-dependent manner. Our results also indicated that treatment of Sprague-Dawley rats with caffeic acid prior to the administration of ketoprofen inhibited oxidative damage and reversed the inhibitory effects of ketoprofen on the antioxidant system and DJ-1 protein expression in the GI mucosa. Our observations suggest that DJ-1 plays an important role in caffeic acid-mediated protection against ketoprofen-induced oxidative damage in the GI mucosa.

  19. Ketoprofen-loaded Eudragit electrospun nanofibers for the treatment of oral mucositis

    Directory of Open Access Journals (Sweden)

    Reda RI

    2017-03-01

    Full Text Available Rana Ihab Reda,1 Ming Ming Wen,2 Amal Hassan El-Kamel1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 2Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt Purpose: The purpose of this study was to formulate ketoprofen (KET-loaded Eudragit L and Eudragit S nanofibers (NFs by the electrospinning technique for buccal administration to treat oral mucositis as a safe alternative to orally administered KET, which causes gastrointestinal tract (GIT side effects. Materials and methods: NFs were prepared by electrospinning using Eudragit L and Eudragit S. Several variables were evaluated to optimize NF formulation, such as polymer types and concentrations, applied voltage, flow rate and drug concentrations. Differential scanning calorimetry (DSC, Fourier transform infrared spectroscopy (FTIR and scanning electron microscopy (SEM and analyses of drug contents, hydration capacity, surface pH, drug release and ex vivo permeation were performed to evaluate the NFs. The selected formulation (F1 was evaluated in vivo on induced oral mucositis in rabbits. Results: SEM revealed that 20% polymer formed smooth and bead-free NFs. DSC results confirmed the amorphous nature of KET in the NFs. FTIR confirmed hydrogen bond formation between the drug and polymer, which stabilized the NFs. Both formulations (F1 and F2 had an acceptable surface pH. The drug loading was >90%. The amount of KET released from NF formulations was statistically significantly higher (P≤0.001 than that released from the corresponding solvent-casted films. The complete release of KET from F1 occurred within 2 hours. Ex vivo permeation study revealed that only a small fraction of drug permeated from F1, which was a better candidate than F2 for local buccal delivery. In vivo evaluation of F1 on oral mucositis induced in rabbits demonstrated that F1 reduced the clinical severity of mucositis in

  20. The Surrogate Method: Past, Present and Future

    Energy Technology Data Exchange (ETDEWEB)

    Lesher, S R; Bernstein, L A; Burke, J T; Lyles, B F; Clark, R M; Fallon, P; Phair, L

    2008-01-09

    The STARS/LiBerACE collaboration has been exploring the surrogate technique with success in the actinide region. This method uses a direct reaction to measure the decay probability of the same compound nucleus produced via a neutron-induced channel. This paper serves as an overview of these activities. Using the STARS array at 88-inch Cyclotron at Lawrence Berkeley National Laboratory we have explored the following surrogate reactions: {sup 234}U({alpha}, {alpha}{prime}f), {sup 235}U({sup 3}He, {alpha}f), {sup 236}U({alpha}, {alpha}{prime}f), {sup 238}U ({alpha},{alpha}{prime}f), {sup 238}U({sup 3}He,{alpha}f), {sup 238}U({sup 3}He, tf) surrogates for {sup 233}U(n,f), {sup 233}U(n,f), {sup 235}U(n,f), {sup 237}U(n,f), {sup 236}U(n,f), and {sup 237}Np(n,f), respectively.

  1. [Biomedical Perspective of the Surrogate Motherhood].

    Science.gov (United States)

    Jouve de la Barreda, Nicolás

    2017-01-01

    The subrogated motherhood takes place when an embryo created by in vitro fertilization (IVF) technology is implanted in a surrogate, sometimes called a gestational mother, by means a contract with her. It can imply to natural families (woman and man) with or without infertility problems, or to monoparental or biparental families of the same sex. Concerning the origin of the gametes used in the IVF emerges different implications on the genetic relationship of the resulting child with the surrogate and the future parents. The subrogated motherhood was initially considered an option to solve infertility problems. Nevertheless this practice has become a possible and attractive option as a source of economic resources for poor women. The cases of benefit of a pregnancy without mediating a contract are exceptional and they are not properly cases of ″subrogated maternity″ but of ″altruistic maternity″ and must be considered as heterologous in vitro fertilization. In this article are analyzed the medical, genetic and bioethics aspects of this new derivation of the fertilization in vitro. As points of special attention are considered the following questions: Is it the surrogate motherhood used preferably to solve infertility problems? Is not this actually a new form of exploitation of the woman? Does not suppose an attack to the natural family? Does not suppose in addition an attack to the dignity of the human being?

  2. Surrogate formulations for thermal treatment of low-level mixed waste. Part 1: Radiological surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Stockdale, J.A.D.; Bostick, W.D.; Hoffmann, D.P. [Martin Marietta Energy Systems, Inc., Oak Ridge, TN (United States); Lee, H.T. [Oak Ridge Associated Universities, TN (United States)

    1994-01-01

    The evaluation and comparison of proposed thermal treatment systems for mixed wastes can be expedited by tests in which the radioactive components of the wastes are replaced by surrogate materials chosen to mimic, as far as is possible, the chemical and physical properties of the radioactive materials of concern. In this work, sponsored by the Mixed Waste Integrated Project of the US Department of Energy, the authors have examined reported experience with such surrogates and suggest a simplified standard list of materials for use in tests of thermal treatment systems. The chief radioactive nuclides of concern in the treatment of mixed wastes are {sup 239}Pu, {sup 238}U, {sup 235}U, {sup 137}Cs, {sup 103}Ru, {sup 99}Tc, and {sup 90}Sr. These nuclides are largely by-products of uranium enrichment, reactor fuel reprocessing, and weapons program activities. Cs, Ru, and Sr all have stable isotopes that can be used as perfect surrogates for the radioactive forms. Technetium exists only in radioactive form, as do plutonium and uranium. If one wishes to preclude radioactive contamination of the thermal treatment system under trial burn, surrogate elements must be chosen for these three. For technetium, the authors suggest the use of natural ruthenium, and for both plutonium and uranium, they recommend cerium. The seven radionuclides listed can therefore be simulated by a surrogate package containing stable isotopes of ruthenium, strontium, cesium, and cerium.

  3. Compatibility study between ketoprofen and pharmaceutical excipients used in solid dosage forms.

    Science.gov (United States)

    Tiţa, Bogdan; Fuliaş, Adriana; Bandur, Geza; Marian, Eleonora; Tiţa, Dumitru

    2011-09-10

    Thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC) techniques were used for assessing the compatibility between ketoprofen (KT) and several excipients as: corn starch, microcrystalline cellulose (PH 101 and PH 102), colloidal silicon dioxide, lactose (monohydrate and anhydre), polyvinylpyrrolidone K30, magnesium stearate and talc, commonly used in the pharmaceutical form. In order to investigate the possible interactions between the components, the thermal curves of KT and each selected excipients were compared with those of their 1:1 (w/w) physical mixtures. For KT, the DSC curves have shown a sharp endothermic peak at 96.8 °C which corresponds to the melting process (literature value: 94-97 °C), respectively the TG curves demonstrated a simple stage of mass loss in the temperature range of 235-400 °C. FT-IR spectroscopy and X-ray powder diffraction (XRPD) were used as complementary techniques to adequately implement and assist in interpretation of the DSC results. On the basis of thermal results, a possible interaction was found between the KT with polyvinylpyrrolidone K30 and magnesium stearate, which could influence the stability of the KT in the binary mixtures. These possible incompatibilities were confirmed by FT-IR and X-ray analysis.

  4. Formulation development of novel in situ nanoemulgel (NEG) of ketoprofen for the treatment of periodontitis.

    Science.gov (United States)

    Srivastava, M; Kohli, K; Ali, M

    2016-01-01

    The aim of the present study was to formulate and evaluate in situ gelling syringeable nanoemulgels (NEGs) of ketoprofen for periodontal delivery. Application of 3-factor 3-level design was employed using the Box-Behnken experimental design for the optimization of nanoemulsion using three independent variables such as percent concentration (v/v) of oil (X1), S mix (mixture of surfactant and cosurfactant) (X2) and water (X3); while the particle size (nm) (Y1), polydispersity index (Y2) and zeta potential (mV) (Y3) were used as dependent variables. The NEG was evaluated based on their drug content, pH measurement, mucoadhesion on the goat buccal mucosa, syringeability and inverted sol-gel transition temperature. The drug release data were analyzed for curve fitting based on the Korsmeyer-Peppas law, and the n-values of optimized A5 and A8 formulations were found 0.3721 and 0.3932, respectively, confirmed that both the formulations followed pseudo Fickian diffusion (n < 0.43). The formulation A8 with the optimal drug release was identified as the best NEG formulation. Results of rheological, mucoadhesion and syringeability studies showed the suitability of desired sol-gel property for periodontal drug delivery. The Herschel-Bulkley model was the best fit model to explain the flow behavior of optimized formulation. Using the HET-CAM method, significantly lower in vitro toxicity was indicated the suitability of developed NEG for intra-pocket delivery.

  5. Ketoprofen encapsulated cucurbit[6]uril nanoparticles: a new exploration of macrocycles for drug delivery

    Science.gov (United States)

    Hoai, Nguyen To; Tuyen Thi Dao, Phuong; Phu, Quoc Nam; Dam Le, Duy; Nguyen, Tuan Anh; Nguyen, Tai Chi; Chien Dang, Mau

    2012-12-01

    The aim of this study is (i) to fabricate a nanoparticle formulation of ketoprofen (Keto) using a relatively new family of macrocycles as the carrier for drug delivery: cucurbit[6]uril (CB[6]), (ii) to evaluate its in vitro dissolution and (iii) to investigate its in vivo pharmaceutical property. The CB[6]-Keto nanoparticles were prepared by emulsion solvent evaporation method. Morphology and size of the successfully prepared nanoparticles were then confirmed using a transmission electron microscope and dynamic light scattering. It was shown that they are spherical with hydrodynamic diameter of 200-300 nm. The in vitro dissolution studies of CB[6]-Keto nanoparticles were conducted at pH 1.2 and 7.4. The results indicated that there is a significant increase in Keto concentration at pH 7.4 compared to pH 1.2. For the in vivo assessment, CB[6]-Keto nanoparticles and referential profenid were administered by oral gavages to rabbits. The results implied that CB[6]-Keto nanoparticles remarkably increased area under the curve compared to profenid.

  6. Ketoprofen removal by O₃ and O₃/UV processes: kinetics, transformation products and ecotoxicity.

    Science.gov (United States)

    Illés, Erzsébet; Szabó, Emese; Takács, Erzsébet; Wojnárovits, László; Dombi, András; Gajda-Schrantz, Krisztina

    2014-02-15

    Ozonation (O3) and its combination with ultraviolet radiation (O3/UV) were used to decompose ketoprofen (KET). Depending on the initial KET concentration, fourteen to fifty time's faster KET degradation was achieved using combined O3/UV method compared to simple ozonation. Using both methods, formation of four major aromatic transformation products were observed: 3-(1-hydroxyethyl)benzophenone, 3-(1-hydroperoxyethyl) benzophenone, 1-(3-benzoylphenyl) ethanone and 3-ethylbenzophenone. In the combined treatment the degradation was mainly due to the direct effect of UV light, however, towards the end of the treatment, O3 highly contributed to the mineralization of small carboxylic acids. High (~90%) mineralization degree was achieved using the O3/UV method. Toxicity tests performed using representatives of three trophic levels of the aquatic ecosystems (producers, consumers and decomposers) Pseudokirchneriella subcapitata green algae, Daphnia magna zooplanktons and Vibrio fischeri bacteria showed that under the used experimental conditions the transformation products have significantly higher toxicity towards all the test organisms, than KET itself. The bacteria and the zooplanktons showed higher tolerance to the formed products than algae. The measured toxicity correlates well with the concentration of the aromatic transformation products, therefore longer treatments than needed for complete degradation of KET are strongly suggested, in order to avoid possible impact of aromatic transformation products on the aquatic ecosystem.

  7. Pharmacokinetics of ketoprofen enantiomers following intravenous and oral administration to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, Heather K; Arthur, Rick M; Steinmetz, Stacy; McKemie, Dan S

    2016-01-01

    Ketoprofen (KTP) is currently only available as an injectable formulation for intravenous administration to horses. The primary goal of the study reported here was to characterize the pharmacokinetics of KTP, including determination of bioavailability following oral administration of the currently available injectable formulation as well as a paste formulation. KTP was administered intravenously and orally, and blood and urine samples were collected at various time points up to 96 h. KTP enantiomer concentrations were determined using LC–MS/MS, and pharmacokinetic analyses were performed. Mean ± standard error values for systemic clearance, steady state volume of distribution and terminal elimination half-life were 0.345 ± 0.033 [R(−) KTP] and 0.167 ± 0.016 [S(+) KTP] L/kg/h, 0.344 ± 0.044 [R(−) KTP] and 0.298 ± 0.025 [S(+) KTP] L/kg, and 2.49 ± 0.077 [R(−) KTP] and 2.86 ± 0.102 [S(+) KTP] h, respectively. Oral bioavailability was calculated as 69.5 ± 10.3% and 88.2 ± 15.9% for R(−) KTP and S(+) KTP, respectively, following administration of the injectable formulation and 53.0 ± 6.0 and 53.0 ± 16.0% for the R(−) KTP and S(+) KTP, respectively, following administration of KTP paste.

  8. Characterization of Ketoprofen/Methyl-β-Cyclodextrin Complexes Prepared Using Supercritical Carbon Dioxide

    Directory of Open Access Journals (Sweden)

    Mauro Banchero

    2013-01-01

    Full Text Available Complexes of methyl-β-cyclodextrin and ketoprofen, a crystalline anti-inflammatory drug with poor water solubility, have been prepared for the first time in the presence of supercritical CO2 at 40°C and 20 MPa. The supercritical treatment allows these pharmaceutical formulations to be prepared without the use of any auxiliary agents or organic solvents. The treated samples were characterized through differential scanning calorimetry, X-ray diffractometry, and the Fourier transform infrared spectroscopy to exclude the presence of crystalline drug and check the formation of the complexes. The increase of the drug dissolution rate was investigated performing in vitro release tests in aqueous solutions. The results showed that the supercritical treatment can be an efficient method to obtain inclusion complexes with enhanced release kinetics. The operating methods of the release tests, that is, the “tablet method” or the “dispersed amount method,” affected both the dissolution rate and its dependence on the drug amount in the samples. On the contrary, the variation of the pH of the dissolution medium did not show any effect on the release rate of the supercritical complexes.

  9. Pharmacokinetics and Antiinflammatory Effect of a Novel Gel System Containing Ketoprofen Solid Nanoparticles.

    Science.gov (United States)

    Nagai, Noriaki; Iwamae, Aya; Tanimoto, Shion; Yoshioka, Chiaki; Ito, Yoshimasa

    2015-01-01

    We previously reported that dermal application using nanoparticles improves skin penetration. In this study, we prepared novel topical formulations containing ketoprofen (KET) solid nanoparticles (KETnano gel ointment) and investigated the antiinflammatory effect of the KET nanoparticle formulations on rheumatoid arthritis using adjuvant-induced arthritis (AA) rats. The KETnano gel ointment was prepared using a bead mill method and additives including methylcellulose and Carbopol 934; the mean particle size of the KET nanoparticles was 83 nm. In the in vitro skin penetration experiment, the penetration rate (Jc) and penetration coefficient through the skin (Kp) values of the KETnano gel ointment were significantly higher than those of gel ointment containing KET microparticles (KETmicro gel ointment; mean particle size 7.7 µm). On the other hand, in the in vivo percutaneous absorption experiment, the apparent absorption rate constant (ka) and the areas under the KET concentration-time curve values in the skin of rats receiving the KETnano gel ointment were significantly higher than those of rats receiving the KETmicro gel ointment, and the amounts of KET in the skin tissues of rats receiving the KETnano gel ointment were also significantly higher than those of rats receiving the KETmicro gel ointment. In addition, the application of the KETnano gel ointment attenuated the enhancement of paw edema of the hind feet of AA rats more than the application of the KETmicro gel ointment. Our findings suggest that a topical drug delivery system using nanoparticles could lead to expansion in the therapeutic use of KET.

  10. Modeling the fate of a photoproduct of ketoprofen in urban rivers receiving wastewater treatment plant effluent.

    Science.gov (United States)

    Hanamoto, Seiya; Hasegawa, Eisuke; Nakada, Norihide; Yamashita, Naoyuki; Tanaka, Hiroaki

    2016-12-15

    Photoproducts of pharmaceuticals have been studied in order not to overlook their potential risks to aquatic organisms. However, no studies have verified an equation for predicting the fate of photoproducts in aquatic environment (Poiger equation) by field measurements, leaving uncertainties in its practical utility. Therefore, we conducted this study to test the applicability of the Poiger equation to 3-ethylbenzophenone (EBP), a photoproduct of ketoprofen (KTP). Photolysis experiments determined the fraction of KTP transformed into EBP as 0.744±0.074 and the quantum yield of EBP degradation as 0.000418±0.000090. Field studies in urban rivers and wastewater treatment plants (WWTPs) revealed that EBP was produced by sunlight, mainly in the rivers, but also appreciably in outdoor primary and secondary clarifiers in the WWTPs. We developed a model in the secondary clarifiers, disinfection tanks, and rivers by incorporating the Poiger equation, which was effective at predicting the concentrations of EBP in the river waters and wastewaters. Thus, our first trial of verification by field measurements enhanced the practical utility of the Poiger equation, though further study including several photoproducts should be conducted. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Stereoselective interaction of ketoprofen enantiomers with β-cyclodextrin: ground state binding and photochemistry.

    Science.gov (United States)

    Marconi, Giancarlo; Mezzina, Elisabetta; Manet, Ilse; Manoli, Francesco; Zambelli, Barbara; Monti, Sandra

    2011-01-01

    The chiral recognition ability of β-cyclodextrin (β-CyD) vs.S- and R-ketoprofen (KP) enantiomers has been studied by circular dichroism (CD), isothermal titration calorimetry (ITC) and NMR. The association constants of the 1 : 1 complexes obtained from CD and ITC titration experiments resulted to be the same for both enantiomers within the experimental uncertainty. Well differentiated CD spectra were determined for the diastereomeric complexes. Their structure was assessed by molecular mechanics and molecular dynamics calculations combined with quantum mechanical calculation of the induced rotational strengths in the low energy KP:β-CyD associates, upon comparison of the calculated quantities with the corresponding experimental CD. The inclusion geometry is similar for both enantiomers with the aromatic carbonyl inserted in the CyD cavity, the monosubstituted ring close to the primary CyD rim and the carboxylate group exposed to the solvent close to the secondary rim. NMR spectra fully confirmed the geometry of the diastereomeric complexes. Tiny structural differences were sensibly probed by CD and confirmed by 2D ROESY spectra. Photoproduct studies with UV absorption and MS detection as well as nanosecond laser flash photolysis evidenced lack of chiral discrimination in the photodecarboxylation of KP within the cavity and formation of a photoaddition product to β-CyD by secondary photochemistry of 3-ethylbenzophenone.

  12. In vitro release and antiinflammatory activity of topical formulations of ketoprofen.

    Science.gov (United States)

    Moretti, M D; Gavini, E; Peana, A T

    2000-01-01

    Ketoprofen (KP) is a potent nonsteroidal anti-inflammatory drug (NSAID) widely used in clinical practice for the control of acute and chronic pain of soft tissues and skeletal muscle system. The importance of KP in the therapeutic field, has stimulated the development of topical dosage forms to improve its percutaneous absorption through the application site. Moreover they could provide relatively consistent drug levels for prolonged periods and avoid gastric irritation, typical side effect of NSAID oral administration. Since the topical formulation efficiency depends on vehicle characteristics, some different ointments, at 1% and 5% concentrations of KP, were evaluated by in vitro and in vivo studies. Among tested ointments, 1% Carbopol cream and 5% Carbopol gel showed the best fluxes of drug through regenerated cellulose membrane. The in vivo percutaneous absorption of KP, evaluated by carrageenan-induced paw edema in rats, showed a good correlation with the in vitro results about considered creams, but the gels in vivo activity was not in according to their in vitro behaviour. The extemporaneous Carbopol cream was able to produce a better edema inhibition than the commercial one, taken as a reference and widely utilized as a topical therapeutic item. About gels, the obtained results were nearly the maximum response considered possible for a topical antiinflammatory drug.

  13. Continuous-flow encapsulation of ketoprofen in copolymer microbeads via co-axial microfluidic device: influence of operating and material parameters on drug carrier properties.

    Science.gov (United States)

    Khan, Ikram Ullah; Serra, Christophe A; Anton, Nicolas; Vandamme, Thierry

    2013-01-30

    Microchannels based microfluidic systems are able to obtain monodispersed microparticles but are limited by cost, time and channel clogging. We succeeded in on the fly encapsulation of high ketoprofen contents in acrylate-based copolymer microbeads by environment friendly UV induced free radical polymerization in off-the-shelf co-axial microfluidic device. FTIR shows complete polymerization of acrylate monomers and interaction between carboxylic group of ketoprofen and ester group of monomers. DSC and XRD confirm amorphous nature of drug in microbeads. Different comonomer content formulations show limited drug release at low pH, a helpful properties to avoid gastric irritating effect of ketoprofen associated with conventional dosage forms. At pH 6.8 microbeads release higher content of drug by a non-Fickian diffusion mechanism. Their drug release rate depends upon the weight content of ethyl acrylate in the formulation as well as their size, increasing by increasing the former and decreasing the later.

  14. A sensitive enzyme-linked immunosorbent assay amplified by biotin-streptavidin system for detecting non-steroidal anti-inflammatory drug ketoprofen.

    Science.gov (United States)

    Bu, Dan; Zhuang, Hui S; Yang, Guang X

    2014-01-01

    A sensitive biotin-streptavidin-amplified enzyme-linked immunosorbent assay (BA-ELISA) method was developed for detecting non-steroidal anti-inflammatory drug ketoprofen. Compared with traditional ELISA method, the sensitivity of proposed immunoassay was enhanced by the biotin-streptavidin system. Under the optimal condition, the median inhibitory concentration (IC50) was 0.25 ng mL(-1), with minor cross-reactivity to a number of structural analogs. This developed assay was successfully applied to detect the ketoprofen residues in different fish samples, and good recoveries (72.6-105.5%) were obtained. The results indicated that this immunoassay method could specifically detect trace ketoprofen residues and could be widely used for routine monitoring of food samples.

  15. THE EFFECT OF SEROTONIN 5-HT1A, 5-HT2 RECEPTOR LIGANDS, KETOPROFEN AND THEIR COMBINATION IN MODELS OF INDUCED PAIN IN MICE.

    Science.gov (United States)

    Zygmunt, Małgorzata; Chłoń-Rzepa, Grażyna; Sapa, Jacek

    2015-01-01

    The present study was carried out to investigate the effects of the 7-(3-chlorophenyl)piperazinylalkyl derivatives of 8-alkoxypurine-2,6-dione (compounds 1-4) in two animal models of induced pain and to compare their effects with ketoprofen and with their combination. All experiments were performed on albino mice. Mice were evaluated for their responsiveness to noxious stimuli using: the hot-plate test and the phenylbenzo-quinone-induced writhing test. All compounds showed analgesic activity only in the writhing test. The analgesic activities of compounds 3 and 4 were similar to ketoprofen. The compounds slightly increased the analgesic effect of ketoprofen when used in combination in the visceral type of pain. The possible mechanisms of the antinociceptive effect of these compounds are thought to involve the activation of analgesic effect mediated by the serotonergic pathways or combination of this mechanism with other important mediators playing a role in pain modulation.

  16. A comparison of intravenous ketoprofen versus pethidine on peri-operative analgesia and post-operative nausea and vomiting in paediatric vitreoretinal surgery.

    Directory of Open Access Journals (Sweden)

    Subramaniam R

    2003-01-01

    Full Text Available AIM: To compare the efficacy of ketoprofen and pethidine for peri-operative analgesia and post-operative nausea and vomiting in children undergoing vitreoretinal surgery and surgery for retinal detachment. MATERIAL AND METHODS: Children aged 7 to 16 years and ASA I status, undergoing vitreo-retinal surgery were randomly allocated to receive either ketoprofen 2mg/kg or pethidine 1mg/kg intravenously for peri-operative analgesia. In all patients, general anaesthesia was induced with thiopentone and intubation was facilitated with vecuronium bromide and maintained with 33% oxygen in nitrous oxide and isoflurane. Intra-operative and post-operative monitoring was done by an observer blinded to the technique. Intra-operative rescue analgesia was used if heart rate and/or blood pressure increased by 25% from pre-incision values. Post-operative pain and episodes of nausea and vomiting were evaluated at recovery (0 hour, 2, 6 and 24 hours intervals. Standard rescue analgesia and anti-emetic agents were administered if required. RESULTS: Eighty-six children were enrolled in the study. Forty-four received ketoprofen while 42 received pethidine. Intra-operative analgesia was comparable in both the groups and no significant difference was found in the requirement of intra-operative rescue analgesia, as well. Postoperatively 6/44 (13.6% children in ketoprofen group had pain at recovery compared to 17/42 (40.4% in pethidine group. Pain at 2, 6 and 24 hours, and postoperative analgesic requirement were not significantly different among the two groups. Post-operative nausea, vomiting, and antiemetic requirement were significantly less in the ketoprofen group at all time intervals. CONCLUSION: Ketoprofen is a satisfactory alternative analgesic to pethidine for vitreoretinal surgery and results in a lower incidence of postoperative nausea and vomiting.

  17. Beneficial effects of Camellia Oil (Camellia oleifera Abel.) on ketoprofen-induced gastrointestinal mucosal damage through upregulation of HO-1 and VEGF.

    Science.gov (United States)

    Cheng, Yu-Ting; Wu, Shu-Li; Ho, Cheng-Ying; Huang, Shang-Ming; Cheng, Chun-Lung; Yen, Gow-Chin

    2014-01-22

    Nonsteroidal anti-inflammatory drugs, such as ketoprofen, are generally used to treat pain and inflammation and as pyretic agents in clinical medicine. However, the usage of these drugs may lead to oxidative injury to the gastrointestinal mucosa. Camellia oil ( Camellia oleifera Abel.) is commonly used in Taiwan and China as cooking oil. Traditional remedies containing this oil exert beneficial health effects on the bowel, stomach, liver, and lungs. However, the effects of camellia oil on ketoprofen-induced oxidative gastrointestinal mucosal lesions remain unknown. The objective of this study was to evaluate the effect of camellia oil on ketoprofen-induced acute gastrointestinal ulcers. The results showed that treatment of Int-407 cells with camellia oil (50-75 μg/mL) not only increased the levels of heme oxygenase-1 (HO-1), glutathione peroxidase (GPx), and superoxide dismutase (SOD) mRNA expression but also increased vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) protein secretion, which served as a mucosal barrier against gastrointestinal oxidative injury. Moreover, Sprague-Dawley (SD) rats treated with camellia oil (2 mL/kg/day) prior to the administration of ketoprofen (50 mg/kg/day) successfully inhibited COX-2 protein expression, inhibited the production of interleukin-6 (IL-6) and nitrite oxide (NO), reversed the impairment of the antioxidant system, and decreased oxidative damage in the gastrointestinal mucosa. More importantly, pretreatment of SD rats with camellia oil strongly inhibited gastrointestinal mucosal injury induced by ketoprofen, which was proved by the histopathological staining of gastrointestinal tissues. Our data suggest that camellia oil exerts potent antiulcer effects against oxidative damage in the stomach and intestine induced by ketoprofen.

  18. Recent Experimental Progress on Surrogate Reactions

    Science.gov (United States)

    Beausang, Cornelius

    2014-09-01

    Reactions on unstable nuclei are important in a wide variety of nuclear physics scenarios. Cross sections for neutron (or light charged particle) induced reactions on target nuclei spanning the chart of the nuclei are important for nuclear astrophysics (r-process, s-process rp- and p-processes etc.), for nuclear energy generation and for national security applications. Many such reactions occur on short-lived unstable nuclei. Even with the present generation of radioactive beam facilities, many such reactions are difficult, if not impossible, to measure directly. For these reactions, often the surrogate reaction technique provides the only option to provide some experimental guidance for the calculations. The experimental and theoretical techniques required are described in some detail in the recent review article by Escher et al.. Originally introduced in the 1970's the last decade has seen a resurgence of interest in the surrogate technique. Various ratio techniques, external, internal and hybrid, have been developed to minimize the effect of target contamination. In the actinide region, a large number of surrogate (n,f) cross sections have been measured. In general, these show agreement to within 5--10%, with directly measured (n,f) data where these data exist (benchmarking), for equivalent neutron energies ranging from ~100 keV up to tens of MeV. For (n, γ) reactions, measurements have been attempted for select nuclei in various mass regions (A ~ 90, 150 and 235) and for these the agreement with directly measured data is less good. The various experimental techniques employed will be described as well as the current state of the experimental data. Some future directions will be described. Reactions on unstable nuclei are important in a wide variety of nuclear physics scenarios. Cross sections for neutron (or light charged particle) induced reactions on target nuclei spanning the chart of the nuclei are important for nuclear astrophysics (r-process, s

  19. Efficacy and safety of ketoprofen lysine salt mouthwash versus benzydamine hydrochloride mouthwash in acute pharyngeal inflammation: a randomized, single-blind study.

    Science.gov (United States)

    Passàli, D; Volonté, M; Passàli, G C; Damiani, V; Bellussi, L

    2001-09-01

    Pharyngodynia, or sore throat, is one of the symptoms most frequently reported by patients to primary care physicians. The purpose of this study was to compare the efficacy and tolerability of mouthwash formulations of ketoprofen lysine salt (KLS), an anti-inflammatory agent, and benzydamine hydrochloride (BH), a local anesthetic, in patients with acute inflammation of the pharyngeal cavity. In this randomized, multicenter, parallel-group, single-blind study, patients (who were blinded) were assigned to receive undiluted BH 15 mL (22.5 mg) or KLS 10 mL (160 mg) diluted in 100 mL of water. Both agents were gargled twice daily until pain remission or up to 7 days. A physical examination of the oropharyngeal cavity was performed, and severity of edema and hyperemia was assessed after 3 days of treatment and, if symptoms had not resolved, after pain remission. Of the 241 patients (120 KLS, 121 BH), 239 were included in the safety analysis and 232 were in the intent-to-treat population. The differences between groups in the duration of analgesic effect after the first dose of drug and the time course of pain were found to be statistically significant (P = 0.006 and P = 0.017, respectively), favoring KLS. Adverse drug-related effects reported included numbness of the tissues in the oral cavity, sensation of tingling in the tissues in the oral cavity, dry mouth, thirst, and nausea. A significantly greater proportion of BH-treated patients reported adverse events (P = 0.001 for all adverse events and drug-related adverse events). KLS mouthwash exerts a significantly longer first-application analgesic action with significantly greater local tolerability than BH in patients with pharyngeal pain of inflammatory and/or infectious origin.

  20. Surrogate Markers of Abdominal Aortic Aneurysm Progression.

    Science.gov (United States)

    Wanhainen, Anders; Mani, Kevin; Golledge, Jonathan

    2016-02-01

    The natural course of many abdominal aortic aneurysms (AAA) is to gradually expand and eventually rupture and monitoring the disease progression is essential to their management. In this publication, we review surrogate markers of AAA progression. AAA diameter remains the most widely used and important marker of AAA growth. Standardized reporting of reproducible methods of measuring AAA diameter is essential. Newer imaging assessments, such as volume measurements, biomechanical analyses, and functional and molecular imaging, as well as circulating biomarkers, have potential to add important information about AAA progression. Currently, however, there is insufficient evidence to recommend their routine use in clinical practice.

  1. Clinical evaluation of postoperative analgesia provided by ketoprofen associated with intravenous or epidural morphine in bitches undergoing ovariosalpingohysterectomy

    Directory of Open Access Journals (Sweden)

    Gabriela Carvalho Aquilino Santos

    2015-04-01

    Full Text Available Multimodal analgesia refers to the practice of combining multiple analgesic drug classes or techniques to target different points along the pain pathway. The objective of this work was to evaluate clinically if ketoprofen associated or not with intravenous or epidural morphine provided adequate postoperative analgesia in bitches undergoing ovariosalpingohysterectomy (OSH. Forty healthy female dogs, weighing 10.7±6.0 kg, sedated with acepromazine (0.05mg kg –1.iv, induced with propofol (5 mg.kg-1. iv and maintained with isoflurane anesthesia, were distributed into four groups of 10 animals each. After stabilization of inhalation anesthesia, the bitches in Miv and CMiv groups received 0.2 mg.kg-1 of morphine intravenously diluted in 10ml of saline; whereas Mep and CMep groups received 0.1mg.kg-1 of epidural morphine. Thirty minutes after premedication, 2.0mg.kg-1.im of ketoprofen was administered in groups CMiv and CMep. Heart and respiratory rate, systolic blood pressure, and rectal temperature were measured. The degree of analgesia was assessed by a blind study in the following 6 hours after surgery, using a descriptive scale and a scale composed by physiologic and behavioral parameters. An statistical analysis was performed using the Tukey-Kramer test and nonparametric Kruskal-Wallis test, with statistical significance of 5%. There was no important difference between the four groups regarding postoperative analgesia, heart and respiratory rate, systolic blood pressure and rectal temperature. According to the results it can be concluded that the use of ketoprofen associated with intravenous or epidural morphine provided adequate and safe analgesia in the first six hours of postoperative in bitches undergoing ovariohysterectomy, suggesting that there was no analgesic potentiation when both agents were combined.

  2. Non-steroidal anti-inflammatory drug for pulmonary administration: design and investigation of ketoprofen lysinate fine dry powders.

    Science.gov (United States)

    Stigliani, Mariateresa; Aquino, Rita P; Del Gaudio, Pasquale; Mencherini, Teresa; Sansone, Francesca; Russo, Paola

    2013-05-01

    Pulmonary inflammation is an important therapeutic target in cystic fibrosis (CF) patients, aiming to limit and delay the lung damage. The purpose of the present research was to produce respirable engineered particles of ketoprofen lysinate, a non-steroidal anti-inflammatory drug able to fight lung inflammatory status by direct administration to the site of action. Micronized drug powders containing leucine as dispersibility enhancer were prepared by co-spray drying the active compound and the excipient from water or hydro-alcoholic feeds. Microparticles were fully characterized in terms of process yield, particle size distribution, morphology and drug content. The ability of the drug to reach the deepest airways after aerosolization of spray-dried formulations was evaluated by Andersen cascade impactor, using the monodose DPI as device. In order to investigate the behaviour of the drug once in contact with lung fluid, an artificial CF mucus was prepared. Drug permeation properties were evaluated interposing the mucus layer between the drug and a synthetic membrane mounted in Franz-type diffusion cells. Finally, the effect of the engineered particles on vitality of human airway epithelial cells of patients homozygous for ΔF 508 CF (CuFi1) was studied and compared to that of raw active compound. Results indicated that powders engineering changed the diameter and shape of the particles, making them suitable for inhalation. The mucus layer in the donor compartment of vertical diffusion cells slowed down drug dissolution and permeation, leucine having no influence. Cell proliferation studies evidenced that the spray drying process together with the addition of leucine reduced the cytotoxic effect of ketoprofen lysine salt as raw material, making the ketoprofen lysinate DPI a very promising product for the inflammation control in CF patients.

  3. Ketoprofen removal by O{sub 3} and O{sub 3}/UV processes: Kinetics, transformation products and ecotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Illés, Erzsébet, E-mail: erzsebet.illes@energia.mta.hu [Environmental Chemistry Research Group Institute of Chemistry, University of Szeged, 6723 Szeged, Tisza Lajos krt. 103 (Hungary); Radiation Chemistry Department, Centre for Energy Research, Hungarian Academy of Sciences, 1121 Budapest, Konkoly Thege M. út 29-33 (Hungary); Szabó, Emese, E-mail: emese.szabo@chem.u-szeged.hu [Environmental Chemistry Research Group Institute of Chemistry, University of Szeged, 6723 Szeged, Tisza Lajos krt. 103 (Hungary); Takács, Erzsébet, E-mail: erzsebet.takacs@energia.mta.hu [Radiation Chemistry Department, Centre for Energy Research, Hungarian Academy of Sciences, 1121 Budapest, Konkoly Thege M. út 29-33 (Hungary); Wojnárovits, László, E-mail: laszlo.wojnarovits@energia.mta.hu [Radiation Chemistry Department, Centre for Energy Research, Hungarian Academy of Sciences, 1121 Budapest, Konkoly Thege M. út 29-33 (Hungary); Dombi, András, E-mail: dombia@chem.uszeged.hu [Environmental Chemistry Research Group Institute of Chemistry, University of Szeged, 6723 Szeged, Tisza Lajos krt. 103 (Hungary); Gajda-Schrantz, Krisztina, E-mail: sranc@chem.u-szeged.hu [Environmental Chemistry Research Group Institute of Chemistry, University of Szeged, 6723 Szeged, Tisza Lajos krt. 103 (Hungary); Department of Inorganic and Analytical Chemistry, University of Szeged, 6720 Szeged, Dóm tér 7 (Hungary); EMPA, Laboratory for High Performance Ceramics, Überlandstrasse 129, 8600 Dübendorf (Switzerland)

    2014-02-01

    Ozonation (O{sub 3}) and its combination with ultraviolet radiation (O{sub 3}/UV) were used to decompose ketoprofen (KET). Depending on the initial KET concentration, fourteen to fifty time's faster KET degradation was achieved using combined O{sub 3}/UV method compared to simple ozonation. Using both methods, formation of four major aromatic transformation products were observed: 3-(1-hydroxyethyl)benzophenone, 3-(1-hydroperoxyethyl) benzophenone, 1-(3-benzoylphenyl) ethanone and 3-ethylbenzophenone. In the combined treatment the degradation was mainly due to the direct effect of UV light, however, towards the end of the treatment, O{sub 3} highly contributed to the mineralization of small carboxylic acids. High (∼ 90%) mineralization degree was achieved using the O{sub 3}/UV method. Toxicity tests performed using representatives of three trophic levels of the aquatic ecosystems (producers, consumers and decomposers) Pseudokirchneriella subcapitata green algae, Daphnia magna zooplanktons and Vibrio fischeri bacteria showed that under the used experimental conditions the transformation products have significantly higher toxicity towards all the test organisms, than KET itself. The bacteria and the zooplanktons showed higher tolerance to the formed products than algae. The measured toxicity correlates well with the concentration of the aromatic transformation products, therefore longer treatments than needed for complete degradation of KET are strongly suggested, in order to avoid possible impact of aromatic transformation products on the aquatic ecosystem. - Highlights: • Ketoprofen degradation is significantly faster using O{sub 3}/UV compared to ozonation. • The presence of O{sub 3} enhances the overall mineralization. • Formation of four major aromatic by-products was observed. • The main step in the decomposition is the decarboxylation. • Degradation products have higher toxicity than ketoprofen itself.

  4. Researeh progression of ketoprofen analysitic method%酮洛芬分析方法的研究进展

    Institute of Scientific and Technical Information of China (English)

    霍文; 孙广利; 董秋香

    2003-01-01

    @@ 酮洛芬(ketoprofen),又名酮基布洛芬,是一种2-芳基丙酸非甾体抗炎药,具有抗炎、镇痛和解热作用,对风湿、类风湿性关节炎、脊髓炎、痛风等有较好疗效.(2000版)收载的酮洛芬制剂有肠溶胶囊和搽剂.此外还有分散片、肠溶片等,本文对其药物分析方法综述如下.

  5. Priority wetland invertebrates as conservation surrogates.

    Science.gov (United States)

    Ormerod, S J; Durance, Isabelle; Terrier, Aurelie; Swanson, Alisa M

    2010-04-01

    Invertebrates are important functionally in most ecosystems, but seldom appraised as surrogate indicators of biological diversity. Priority species might be good candidates; thus, here we evaluated whether three freshwater invertebrates listed in the U.K. Biodiversity Action Plan indicated the richness, composition, and conservation importance of associated wetland organisms as defined respectively by their alpha diversity, beta diversity, and threat status. Sites occupied by each of the gastropods Segmentina nitida, Anisus vorticulus, and Valvata macrostoma had greater species richness of gastropods and greater conservation importance than other sites. Each also characterized species assemblages associated with significant variations between locations in alpha or beta diversity among other mollusks and aquatic macrophytes. Because of their distinct resource requirements, conserving the three priority species extended the range of wetland types under management for nature conservation by 18% and the associated gastropod niche-space by around 33%. Although nonpriority species indicated variations in richness, composition, and conservation importance among other organisms as effectively as priority species, none characterized such a wide range of high-quality wetland types. We conclude that priority invertebrates are no more effective than nonpriority species as indicators of alpha and beta diversity or conservation importance among associated organisms. Nevertheless, conserving priority species can extend the array of distinct environments that are protected for their specialized biodiversity and environmental quality. We suggest that this is a key role for priority species and conservation surrogates more generally, and, on our evidence, can best be delivered through multiple species with contrasting habitat requirements.

  6. Estimating Predictability Redundancy and Surrogate Data Method

    CERN Document Server

    Pecen, L

    1995-01-01

    A method for estimating theoretical predictability of time series is presented, based on information-theoretic functionals---redundancies and surrogate data technique. The redundancy, designed for a chosen model and a prediction horizon, evaluates amount of information between a model input (e.g., lagged versions of the series) and a model output (i.e., a series lagged by the prediction horizon from the model input) in number of bits. This value, however, is influenced by a method and precision of redundancy estimation and therefore it is a) normalized by maximum possible redundancy (given by the precision used), and b) compared to the redundancies obtained from two types of the surrogate data in order to obtain reliable classification of a series as either unpredictable or predictable. The type of predictability (linear or nonlinear) and its level can be further evaluated. The method is demonstrated using a numerically generated time series as well as high-frequency foreign exchange data and the theoretical ...

  7. Modulation by gamithromycin and ketoprofen of in vitro and in vivo porcine lipopolysaccharide-induced inflammation.

    Science.gov (United States)

    Wyns, Heidi; Meyer, Evelyne; Plessers, Elke; Watteyn, Anneleen; van Bergen, Thomas; Schauvliege, Stijn; De Baere, Siegrid; Devreese, Mathias; De Backer, Patrick; Croubels, Siska

    2015-12-15

    The immunomodulatory properties of gamithromycin (GAM), ketoprofen (KETO) and their combination (GAM-KETO) were investigated after both in vitro and in vivo lipopolysaccharide (LPS)-induced inflammation. The influence of these drugs was measured on the production of prostaglandin E2 (PGE2) and the pro-inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in both LPS-stimulated porcine peripheral blood mononuclear cells (PBMCs) and LPS-challenged pigs. Additionally, effects on the production of acute phase proteins (APPs), including pig major acute phase protein (pig-MAP) and C-reactive protein (CRP), as well as on the development of fever, pulmonary symptoms and sickness behaviour were investigated. Dexamethasone was included as a positive control in the in vitro research. Following an 18h-incubation period with 1.25μg/mL LPS, the levels of TNF-α, IL-1β and IL-6 (p<0.05) measured in the PBMC supernatants were significantly increased. Incubation with a high concentration of both GAM and KETO significantly reduced the in vitro levels of all three cytokines. Maximal plasma concentrations of TNF-α and IL-6 were observed at 1h and 2.5h following LPS challenge in pigs, respectively. Neither GAM, nor KETO nor the combination GAM-KETO was able to inhibit the in vivo LPS-induced cytokine production. Furthermore, none of the drugs influenced the subsequent APPs production. In contrast, administration of KETO significantly reduced PGE2 production both in vitro and in vivo (p<0.05 and p<0.001, respectively) and prevented the development of fever and severe symptoms, including dyspnoea, anorexia, vomiting and lateral decubitus.

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

    Science.gov (United States)

    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.

  9. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage

    Directory of Open Access Journals (Sweden)

    M. Kaleemullah

    2017-07-01

    Full Text Available Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor (f2 value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05 between the F3 and reference drug in terms of MDT and

  10. A Method of Surrogate Model Construction which Leverages Lower-Fidelity Information using Space Mapping Techniques

    Science.gov (United States)

    2014-03-27

    errors found using the polynomial response surrogate (LS PRM ) overlaid on the data from the space-mapped (SM) surrogate...nonlinear space-mapped surrogate responses, with the least-squares PRM surrogate response plotted for comparison . . . . . . . . . . . . . . . . . 65 42...Percent error comparison between the least-squares space-mapping and the PRM surrogate models derived from samples in the second dataset

  11. Comparison of the effects of ketoprofen and flunixin meglumine on the in vitro response of equine peripheral blood monocytes to bacterial endotoxin.

    Science.gov (United States)

    Jackman, B R; Moore, J N; Barton, M H; Morris, D D

    1994-04-01

    The purpose of this study was to investigate the in vitro effects of flunixin meglumine, a cyclo-oxygenase inhibitor, and ketoprofen, a reported cyclo-oxygenase and lipoxygenase inhibitor, on the synthesis of cyclo-oxygenase end-products thromboxane B2 and prostaglandin E2, lipoxygenase derived 12-hydroxyeicosatetraenoic acid, tumor necrosis factor and tissue factor. Six adult horses were each randomly administered flunixin meglumine (1.1 mg/kg) or ketoprofen (2.2 mg/kg) intravenously every 12 hours with the drug treatments separated by two weeks. Blood samples were obtained prior to initiating treatment, the last day of treatment and for two consecutive days after the termination of treatment for measurement of serum concentrations of thromboxane B2 as well as isolation of peripheral blood monocytes. Quantitation of unstimulated, endotoxin- and calcium ionophore-induced synthesis of thromboxane B2, prostaglandin E2, 12-hydroxyeicosatetraenoic acid, tumor necrosis factor and tissue factor by peripheral blood monocytes was performed in vitro. Both flunixin meglumine and ketoprofen significantly decreased serum concentrations of thromboxane B2 demonstrating in vivo cyclo-oxygenase inhibition. There were no significant differences between drug treatment groups in the in vitro production of thromboxane B2, prostaglandin E2, 12-hydroxy-eicosatetraenoic acid, tumor necrosis factor or tissue factor. This study does not identify significant differences between the effects of flunixin meglumine and ketoprofen.

  12. Ester Prodrugs of Ketoprofen: Synthesis, In Vitro Stability, In Vivo Biological Evaluation and In Silico Comparative Docking Studies Against COX-1 and COX-2.

    Science.gov (United States)

    Ahmed, Musa; Azam, Faizul; Gbaj, Abdul; Zetrini, Abdulmottaleb E; Abodlal, Amna Salem; Rghigh, Abir; Elmahdi, Eman; Hamza, Amel; Salama, Mabruk; Bensaber, Salah M

    2016-01-01

    Prompted by the ineptness of the currently used non-steroidal antiinflammatory drugs (NSAIDs) to control gastric mucosal and renal adverse reactions, several ester prodrugs of ketoprofen were synthesized and characterized by IR, 1H NMR and mass spectral data. Physicochemical properties such as aqueous solubility, octanol-water partition coefficient log P, chemical stability and enzymatic hydrolysis of the synthesized molecules have been studied to assess their potential as prodrugs. The obtained results confirmed that all ester prodrugs are chemically stable, possess increased lipophilicity compared to their parent compounds and converted to the active drugs in vivo. All of the tested ester prodrugs exhibited marked anti-inflammatory activity ranging from 91.8% to 113.3% in comparison with the parent drug, ketoprofen. A mutual prodrug obtained from two antiinflammatory molecules, ketoprofen and salicylic acid has been noted to potentiate the activity making it most active molecule of the series. The ulcerogenic index of the ester prodrugs was significantly lower than the parent drug, ketoprofen. Comparative docking studies against X-ray crystal structures of COX-1 and COX-2 further provided understanding of their interaction with the cyclooxygenases that will facilitate design of better inhibitors (or prodrugs) with sufficient specificity for COX-2 against COX-1. The study offers an innovative strategy for finding a molecule with safer therapeutic profile for longterm treatment of inflammatory diseases.

  13. Multi-spectroscopic method study the interaction of anti-inflammatory drug ketoprofen and calf thymus DNA and its analytical application

    Science.gov (United States)

    Guo, Hongqin; Cai, Changqun; Gong, Hang; Chen, Xiaoming

    2011-06-01

    Interactions of the anti-inflammatory drug ketoprofen with calf thymus DNA (ctDNA) in aqueous solution have been studied by multi-spectroscopic method including resonance light scattering (RLS) technique, ultraviolet spectra (UV), 1H NMR, etc. The characteristics of RLS spectra, the effective factors and optimum conditions of the reaction have been unequivocally investigated. Mechanism investigations have shown that ketoprofen can bind to ctDNA by groove binding and form large particles, which resulted in the enhancement of RLS intensity. In Critic acid-Na 2HPO 4 buffer (pH = 6.5), ketoprofen has a maximum peak 451.5 nm and the RLS intensity is remarkably enhanced by trace amount of ctDNA due to the interaction between ketoprofen and ctDNA. The enhancement of RLS signal is directly proportional to the concentration of ctDNA in the range of 1.20 × 10 -6-1.0 × 10 -5 mol/L, and its detection limit (3 σ) is 1.33 × 10 -9 mol/L. The method is simple, rapid, practical and relatively free from interference generated by coexisting substance, and was applied to the determination of trace amounts of nucleic acid in synthetic samples with satisfactory results.

  14. [The clinical estimation of ketoprofen lysine salt effect on the intensitivity of acute pain syndrome in the oral cavity during surgical procedures and postoperative period].

    Science.gov (United States)

    Durnovo, E A; Shashurina, S V; Bespalova, N A; Khomutinnikova, N E; Gliavina, I A; Marochkina, M S; Iartseva, A V

    2013-01-01

    Is studying and control of the clinical efficacy and safety of ketoprofen lysine salt (КLS) (the commercial name is "Oki" manufacturer by Dompe CPA, Italy) in the form of sachets and solutions for application in postoperative period after dental surgeries procedures. The comparison of the analgetic effect of systemic and local forms of the "Oki" drug, depending on the type and extent of surgery procedures. Was carried out surgical treatment and patients examination in the postoperative period. Surgical procedures included: vestibulolasty, vestibulolasty with apically-displaced flap, vestibulolasty with apically-displaced flap and a free palatal mucogingival graft, removal impacted and dystopic teeth, periodontal surgery. The research was conducted in the Surgical stomatology and Maxillofacial surgery Department (stomatological policlinic of the Nizhny Novgorod State Medical Academy). Was noted rapid advanced of anesthesia when using sachets and solutions of the ketoprofen lysine salt (the commercial name is "Oki" manufacturer by Dompe CPA, Italy) in postoperative period after dental surgical procedures. Was noted a more advanced of analgetic effect in the application therapy by DCI solution when open surgical wound presented. Analgetic effect was observed after 20-30 min and was maintained in the postoperative period to an average of 8 hours. Local application sachets and solution of the ketoprofen lysine salt (KLS ), in our opinion, is the most appropriate and is highly effective when open surgical wound presented. Ketoprofen lysine salt (KLS) has a neutral pH and does not irritate the gastrointestinal tract, that determines the safety of its used.

  15. Comparative efficacy of nimesulide and ketoprofen on inflammatory events in third molar surgery: a split-mouth, prospective, randomized, double-blind study.

    Science.gov (United States)

    Pouchain, E C; Costa, F W G; Bezerra, T P; Soares, E C S

    2015-07-01

    This study aimed to compare the effect of nimesulide and ketoprofen on inflammatory parameters related to the surgical removal of third molars. A split-mouth, prospective, randomized, double-blind study was conducted in patients undergoing removal of four third molars. Eighteen eligible patients were allocated to one of two groups to receive treatment two times a day with either ketoprofen 100 mg or nimesulide 100 mg for a period of 3 days. The rescue medication intake (number) and pain intensity were evaluated at 6, 12, 24, and 48 h, and at 7 days postoperatively. Swelling and maximum mouth opening were evaluated at 24 h, 72 h, and 7 days postoperatively. The peak pain score occurred at 6h after surgery in the nimesulide group and at 12h in the ketoprofen group. There was no statistically significant difference between the groups, although pain relief was observed after 48 h in the nimesulide group and after 7 days in the ketoprofen group. For each group, there was a statically significant difference in pain scores among the studied periods (PKetoprofen and nimesulide were effective at controlling pain, swelling, and trismus after the surgical removal of third molars.

  16. Comparison of the effects of ketoprofen and flunixin meglumine on the in vitro response of equine peripheral blood monocytes to bacterial endotoxin.

    Science.gov (United States)

    Jackman, B R; Moore, J N; Barton, M H; Morris, D D

    1994-01-01

    The purpose of this study was to investigate the in vitro effects of flunixin meglumine, a cyclo-oxygenase inhibitor, and ketoprofen, a reported cyclo-oxygenase and lipoxygenase inhibitor, on the synthesis of cyclo-oxygenase end-products thromboxane B2 and prostaglandin E2, lipoxygenase derived 12-hydroxyeicosatetraenoic acid, tumor necrosis factor and tissue factor. Six adult horses were each randomly administered flunixin meglumine (1.1 mg/kg) or ketoprofen (2.2 mg/kg) intravenously every 12 hours with the drug treatments separated by two weeks. Blood samples were obtained prior to initiating treatment, the last day of treatment and for two consecutive days after the termination of treatment for measurement of serum concentrations of thromboxane B2 as well as isolation of peripheral blood monocytes. Quantitation of unstimulated, endotoxin- and calcium ionophore-induced synthesis of thromboxane B2, prostaglandin E2, 12-hydroxyeicosatetraenoic acid, tumor necrosis factor and tissue factor by peripheral blood monocytes was performed in vitro. Both flunixin meglumine and ketoprofen significantly decreased serum concentrations of thromboxane B2 demonstrating in vivo cyclo-oxygenase inhibition. There were no significant differences between drug treatment groups in the in vitro production of thromboxane B2, prostaglandin E2, 12-hydroxy-eicosatetraenoic acid, tumor necrosis factor or tissue factor. This study does not identify significant differences between the effects of flunixin meglumine and ketoprofen. PMID:8004539

  17. Effects of flunixin, tolfenamic acid, R(-) and S(+) ketoprofen on the response of equine synoviocytes to lipopolysaccharide stimulation.

    Science.gov (United States)

    Landoni, M F; Foot, R; Frean, S; Lees, P

    1996-11-01

    The objective of this study was to analyse the effects of 4 nonsteroidal anti-inflammatory drugs (NSAIDs) on the production of beta-glucuronidase (beta-glu), tumour necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interleukin-1 (IL-1) and prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-stimulated equine synoviocytes. The agents studied were flunixin, tolfenamic acid, S(+)ketoprofen (KTP) and R(-)ketoprofen. LPS-induced release of beta-glu from synoviocytes was inhibited in a concentration dependent manner by all 4 compounds, tolfenamic acid being the most potent. Of the 2 KTP enantiomers, S(+)KTP exerted the greatest inhibitory effect. Tolfenamic acid and flunixin increased the production of IL-6-like activity by LPS-stimulated synoviocytes only at the highest concentration studied (1000 mumol/l). Lower concentrations produced no effect on IL-6. Flunixin, tolfenamic acid and S(+)KTP produced statistically significant and concentration related increases in the release of IL-1-like activity by LPS-stimulated synoviocytes. Prostaglandin E2 synthesis was markedly inhibited in a concentration dependent manner by the 4 NSAIDs. However, R(-)KTP was effective only at the highest concentrations investigated (1000 and 100 mumol/l). The present findings are compatible with the possibility that longterm use of NSAIDs in arthropathies, by removing the regulator role of PGE2 on IL-1 synthesis, might enhance the pathological process of cartilage degeneration.

  18. Analysis of chiral non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac binding with HSA

    Institute of Scientific and Technical Information of China (English)

    Chang-Chuan Guo; Yi-Hong Tang; Hai-Hong Hu; Lu-Shan Yu; Hui-Di Jiang; Su Zeng

    2011-01-01

    The protein binding of non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac with human serum albumin (HSA) was investigated using indirect chiral high performance liquid chromatography (HPLC) and ultrafiltration techniques. S-(-)-1-(1-naphthyl)- ethylamine (S-NEA) was utilized as chiral derivatization reagent and pre-column derivatization RP-HPLC method was established for the separation and assay of the three pairs of enantiomer. The method had good linear relationship over the investigated concentration range without interference. The average extraction efficiency was higher than 85% in different systems, and the intra-day and inter-day precisions were less than 15%. In serum albumin, the protein binding of etodolac enantiomers showed significant stereoselectivity that the affinity of S-enantiomer was stronger than R-enantiomer, and the stereoselectivity ratio reached 6.06; Flurbiprofen had only weak stereoselectivity in HSA, and ketoprofen had no stereoselectivity at all. Scatchard curves showed that all the three chiral drugs had two types of binding sites in HSA.

  19. Ketoprofen-loaded Eudragit RSPO microspheres: an influence of sodium carbonate on in vitro drug release and surface topology.

    Science.gov (United States)

    Pandit, Sachin S; Hase, Dinesh P; Bankar, Manish M; Patil, Arun T; Gaikwad, Naresh J

    2009-05-01

    Eudragit RSPO microspheres containing ketoprofen as model drug, prepared by solvent evaporation technique using acetone-liquid paraffin (heavy) solvent system were examined. Depending upon polymer concentration in the internal phase, microspheres of particle mean diameter (122.8, 213.6 and 309.5 μm) were obtained. The influence of surface washing of microspheres with n-hexane, i.e. untreated microspheres (UM) on the drug content, drug release and surface topology of microspheres were compared to those of microspheres washed with sodium carbonate, i.e. treated microspheres (TM) in order to make the non-encapsulated surface drug soluble. The significant reduction in encapsulation efficiency (p removes a significant amount of drug (p microsphere polymer matrix. Scanning electron microscopy (SEM) examination revealed that the removal of surface drug did not affect the size of microspheres but the topology of treated smallest microspheres was modified. The ketoprofen release profiles were examined in phosphate buffer pH 7.4, using USPXXIII paddle type dissolution apparatus. In general both UM and TM result in biphasic release patterns, but the initial burst effect (first release phase) of TM was lower than that of UM. The second release phase did not change for the bigger size but increased for the smallest microspheres, probably owing to the modification of matrix porosity.

  20. Surrogate Modeling for Geometry Optimization in Material Design

    DEFF Research Database (Denmark)

    Rojas Larrazabal, Marielba de la Caridad; Abraham, Yonas B.; Holzwarth, Natalie A.W.;

    2007-01-01

    We propose a new approach based on surrogate modeling for geometry optimization in material design. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)......We propose a new approach based on surrogate modeling for geometry optimization in material design. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)...

  1. Human surrogate neck response to +Gz vertical impact

    NARCIS (Netherlands)

    Rooij, L. van; Uittenbogaard, J.

    2011-01-01

    For the evaluation of impact scenarios with a substantial vertical component, the performance of current human surrogates - the RID 3D hardware dummy and two numerical human models - was evaluated. Volunteer tests with 10G and 6G pulses were compared to reconstructed tests with human surrogates.

  2. Term clouds as surrogates for user generated speech

    NARCIS (Netherlands)

    M. Tsagkias; M. Larson; M. de Rijke

    2008-01-01

    User generated spoken audio remains a challenge for Automatic Speech Recognition (ASR) technology and content-based audio surrogates derived from ASR-transcripts must be error robust. An investigation of the use of term clouds as surrogates for podcasts demonstrates that ASR term clouds closely appr

  3. INTEC SBW Solid Sludge Surrogate Recipe and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Maio, Vince; Janikowski, Stuart; Johnson, Jim; Maio, Vince; Pao, Jenn-Hai

    2004-06-01

    A nonhazardous INTEC tank farm sludge surrogate that incorporated metathesis reactions to generate solids from solutions of known elements present in the radioactive INTEC tank farm sodium-bearing waste sludges was formulated. Elemental analyses, physical property analyses, and filtration testing were performed on waste surrogate and tank farm waste samples, and the results were compared. For testing physical systems associated with moving the tank farm solids, the surrogate described in this report is the best currently available choice. No other available surrogate exhibits the noted similarities in behavior to the sludges. The chemical morphology, particle size distribution, and settling and flow characteristics of the surrogate were similar to those exhibited by the waste sludges. Nonetheless, there is a difference in chemical makeup of the surrogate and the tank farm waste. If a chemical treatment process were to be evaluated for final treatment and disposition of the waste sludges, the surrogate synthesis process would likely require modification to yield a surrogate with a closer matching chemical composition.

  4. Inactivation of Tulane virus, a novel surrogate for human norovirus

    Science.gov (United States)

    Human noroviruses (HuNoVs) are the major cause of non-bacterial epidemics of gastroenteritis. Due to the inability to cultivate HuNoVs and the lack of an efficient small animal model, surrogates are used to study HuNoV biology. Two such surrogates, the feline calicivirus (FCV) and the murine norovir...

  5. Human surrogate neck response to +Gz vertical impact

    NARCIS (Netherlands)

    Rooij, L. van; Uittenbogaard, J.

    2011-01-01

    For the evaluation of impact scenarios with a substantial vertical component, the performance of current human surrogates - the RID 3D hardware dummy and two numerical human models - was evaluated. Volunteer tests with 10G and 6G pulses were compared to reconstructed tests with human surrogates. Add

  6. Space Mapping Optimization of Microwave Circuits Exploiting Surrogate Models

    DEFF Research Database (Denmark)

    Bakr, M. H.; Bandler, J. W.; Madsen, Kaj

    2000-01-01

    A powerful new space-mapping (SM) optimization algorithm is presented in this paper. It draws upon recent developments in both surrogate model-based optimization and modeling of microwave devices, SM optimization is formulated as a general optimization problem of a surrogate model. This model...

  7. Preclinical and human surrogate models of itch

    DEFF Research Database (Denmark)

    Hoeck, Emil August; Marker, Jens Broch; Gazerani, Parisa;

    2016-01-01

    Pruritus, or simply itch, is a debilitating symptom that significantly decreases the quality of life in a wide range of clinical conditions. While histamine remains the most studied mediator of itch in humans, treatment options for chronic itch, in particular antihistamine-resistant itch, are lim...... currently applied in animals and humans. This article is protected by copyright. All rights reserved.......Pruritus, or simply itch, is a debilitating symptom that significantly decreases the quality of life in a wide range of clinical conditions. While histamine remains the most studied mediator of itch in humans, treatment options for chronic itch, in particular antihistamine-resistant itch......, are limited. Relevant preclinical and human surrogate models of non-histaminergic itch are needed to accelerate the development of novel antipruritics and diagnostic tools. Advances in basic itch research have facilitated the development of diverse models of itch and associated dysesthesiae. While...

  8. Surrogates of plutonium for detection equipment testing

    Science.gov (United States)

    Peerani, Paolo; Tomanin, Alice

    2011-10-01

    Fight against illicit trafficking of nuclear material relies on the possibility to detect nuclear material concealed in vehicles, people or cargo containers. This is done by equipping and training law enforcement and security staff in border stations or other points of access to strategic places and critical infrastructures with radiation detection equipment. The design, development, testing and evaluation of these instruments ideally require the use of real nuclear material to assess, verify and certify their detection performance. Availability of special nuclear material may be an issue, especially for industry, since only few specialized laboratories are licensed for such material. This paper tries to analyse and describe the possibility to use suitable surrogates that may replace the use of real nuclear material in testing the detection capabilities of instruments used in nuclear security.

  9. [Surrogate maternity--literature review and practice].

    Science.gov (United States)

    Pilka, L; Rumpík, D; Pilka, R; Koudelka, M; Prudil, L

    2009-04-01

    This review summarizes opinions on surrogacy including internatinal and governmental organizations attitudes, as well as some religious concerns. Literature review. Reprofit International, Brno, Reproductive medicine and gynecology centre, Zlin, Department of obstetrics and gynecology, Palacky University, Olomouc. The developments in the field of assissted reproduction during the last twenty years have attracted unexpected public interest in some of its ethical and moral aspects. It is very difficult to find a uniform attitude to ethical concerns of assisted conception in plural society. Surrogate mother is defined as a woman who bears and relinquishes a child for another person. The european congress on human reproduction in Barcelona 2008 adopted following résumé on surrogacy: Public opinion has shifted to a position where surrogacy is recognized as an appropriate response to infertility in some circumstances and it is to be expected that this approach will be further strenghtened with stress on positive aspects of familiar life.

  10. Tractable Experiment Design via Mathematical Surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Brian J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-29

    This presentation summarizes the development and implementation of quantitative design criteria motivated by targeted inference objectives for identifying new, potentially expensive computational or physical experiments. The first application is concerned with estimating features of quantities of interest arising from complex computational models, such as quantiles or failure probabilities. A sequential strategy is proposed for iterative refinement of the importance distributions used to efficiently sample the uncertain inputs to the computational model. In the second application, effective use of mathematical surrogates is investigated to help alleviate the analytical and numerical intractability often associated with Bayesian experiment design. This approach allows for the incorporation of prior information into the design process without the need for gross simplification of the design criterion. Illustrative examples of both design problems will be presented as an argument for the relevance of these research problems.

  11. Sheet metal forming optimization by using surrogate modeling techniques

    Science.gov (United States)

    Wang, Hu; Ye, Fan; Chen, Lei; Li, Enying

    2017-01-01

    Surrogate assisted optimization has been widely applied in sheet metal forming design due to its efficiency. Therefore, to improve the efficiency of design and reduce the product development cycle, it is important for scholars and engineers to have some insight into the performance of each surrogate assisted optimization method and make them more flexible practically. For this purpose, the state-of-the-art surrogate assisted optimizations are investigated. Furthermore, in view of the bottleneck and development of the surrogate assisted optimization and sheet metal forming design, some important issues on the surrogate assisted optimization in support of the sheet metal forming design are analyzed and discussed, involving the description of the sheet metal forming design, off-line and online sampling strategies, space mapping algorithm, high dimensional problems, robust design, some challenges and potential feasible methods. Generally, this paper provides insightful observations into the performance and potential development of these methods in sheet metal forming design.

  12. Environmental diversity as a surrogate for species representation.

    Science.gov (United States)

    Beier, Paul; de Albuquerque, Fábio Suzart

    2015-10-01

    Because many species have not been described and most species ranges have not been mapped, conservation planners often use surrogates for conservation planning, but evidence for surrogate effectiveness is weak. Surrogates are well-mapped features such as soil types, landforms, occurrences of an easily observed taxon (discrete surrogates), and well-mapped environmental conditions (continuous surrogate). In the context of reserve selection, the idea is that a set of sites selected to span diversity in the surrogate will efficiently represent most species. Environmental diversity (ED) is a rarely used surrogate that selects sites to efficiently span multivariate ordination space. Because it selects across continuous environmental space, ED should perform better than discrete surrogates (which necessarily ignore within-bin and between-bin heterogeneity). Despite this theoretical advantage, ED appears to have performed poorly in previous tests of its ability to identify 50 × 50 km cells that represented vertebrates in Western Europe. Using an improved implementation of ED, we retested ED on Western European birds, mammals, reptiles, amphibians, and combined terrestrial vertebrates. We also tested ED on data sets for plants of Zimbabwe, birds of Spain, and birds of Arizona (United States). Sites selected using ED represented European mammals no better than randomly selected cells, but they represented species in the other 7 data sets with 20% to 84% effectiveness. This far exceeds the performance in previous tests of ED, and exceeds the performance of most discrete surrogates. We believe ED performed poorly in previous tests because those tests considered only a few candidate explanatory variables and used suboptimal forms of ED's selection algorithm. We suggest future work on ED focus on analyses at finer grain sizes more relevant to conservation decisions, explore the effect of selecting the explanatory variables most associated with species turnover, and investigate

  13. Desorption of a methamphetamine surrogate from wallboard under remediation conditions

    Science.gov (United States)

    Poppendieck, Dustin; Morrison, Glenn; Corsi, Richard

    2015-04-01

    Thousands of homes in the United States are found to be contaminated with methamphetamine each year. Buildings used to produce illicit methamphetamine are typically remediated by removing soft furnishings and stained materials, cleaning and sometimes encapsulating surfaces using paint. Methamphetamine that has penetrated into paint films, wood and other permanent materials can be slowly released back into the building air over time, exposing future occupants and re-contaminating furnishings. The objective of this study was to determine the efficacy of two wallboard remediation techniques for homes contaminated with methamphetamine: 1) enhancing desorption by elevating temperature and relative humidity while ventilating the interior space, and 2) painting over affected wallboard to seal the methamphetamine in place. The emission of a methamphetamine surrogate, N-isopropylbenzylamine (NIBA), from pre-dosed wallboard chambers over 20 days at 32 °C and two values of relative humidity were studied. Emission rates from wallboard after 15 days at 32 °C ranged from 35 to 1400 μg h-1 m-2. Less than 22% of the NIBA was removed from the chambers over three weeks. Results indicate that elevating temperatures during remediation and latex painting of impacted wallboard will not significantly reduce freebase methamphetamine emissions from wallboard. Raising the relative humidity from 27% to 49% increased the emission rates by a factor of 1.4. A steady-state model of a typical home using the emission rates from this study and typical residential building parameters and conditions shows that adult inhalation reference doses for methamphetamine will be reached when approximately 1 g of methamphetamine is present in the wallboard of a house.

  14. Effect of metal complexation to anti-inflammatory over the action against oxidative and free radicals: ketoprofen action; Efeito da complexacao de metais aos antiinflamatorios na acao contra agentes oxidativos e radicais livres: acao do cetoprofeno

    Energy Technology Data Exchange (ETDEWEB)

    Manente, Francine Alessandra; Mello, Lucas Rosolen de Almeida; Vellosa, Jose Carlos Rebuglio [UEPG, Universidade Estadual de Ponta Grossa, Departamento de Analises Clinicas eToxicologicas, Ponta Grossa, PR (Brazil); Khalil, Omar Arafat Kdudsi [IFG, Instituto Federal de Goias, Campus de Formosa, Formosa - GO (Brazil); Carvalho, Claudio Teodoro de [UFGD, Universidade Federal da Grande Dourados, Faculdade de Ciencias Exatas e Tecnologias, Dourados-MS (Brazil); Bannach, Gilbert [UNESP, Universidade Estadual Paulista Julio de Mesquita Filho, Faculdade de Ciencias de Bauru, Bauru, SP (Brazil)

    2011-07-01

    Free radicals are highly reactive species generated in living organisms for the purpose of protection. However, in some circumstances, they are responsible for the occurrence or aggravation of tissue damage. Many anti-inflammatory drugs have a direct effect on free radicals and not radical reactive species, which contributes to its actions against inflammation. Ketoprofen is a nonsteroidal anti-inflammatory agent that generates free radicals by photo irradiation and has an important hemolytic effect with that. The complexation of metals to different drugs has been used as a strategy to improve the pharmacological action of different molecules and reduce their side effects. This paper presents the results of ketoprofen and their metallic complexes action on erythrocytes and free radicals. It was observed that the cerium enhances the scavenger properties of ketoprofen on free radicals, while copper enhances its action over non-radical oxidants. Copper also reduced the hemolytic effect presented by ketoprofen meanwhile its cerium derivative maintained it. (author)

  15. Ketoprofen-loaded Eudragit electrospun nanofibers for the treatment of oral mucositis

    Science.gov (United States)

    Reda, Rana Ihab; Wen, Ming Ming; El-Kamel, Amal Hassan

    2017-01-01

    Purpose The purpose of this study was to formulate ketoprofen (KET)-loaded Eudragit L and Eudragit S nanofibers (NFs) by the electrospinning technique for buccal administration to treat oral mucositis as a safe alternative to orally administered KET, which causes gastrointestinal tract (GIT) side effects. Materials and methods NFs were prepared by electrospinning using Eudragit L and Eudragit S. Several variables were evaluated to optimize NF formulation, such as polymer types and concentrations, applied voltage, flow rate and drug concentrations. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) and analyses of drug contents, hydration capacity, surface pH, drug release and ex vivo permeation were performed to evaluate the NFs. The selected formulation (F1) was evaluated in vivo on induced oral mucositis in rabbits. Results SEM revealed that 20% polymer formed smooth and bead-free NFs. DSC results confirmed the amorphous nature of KET in the NFs. FTIR confirmed hydrogen bond formation between the drug and polymer, which stabilized the NFs. Both formulations (F1 and F2) had an acceptable surface pH. The drug loading was >90%. The amount of KET released from NF formulations was statistically significantly higher (P≤0.001) than that released from the corresponding solvent-casted films. The complete release of KET from F1 occurred within 2 hours. Ex vivo permeation study revealed that only a small fraction of drug permeated from F1, which was a better candidate than F2 for local buccal delivery. In vivo evaluation of F1 on oral mucositis induced in rabbits demonstrated that F1 reduced the clinical severity of mucositis in rabbits under the current experimental conditions. The attenuated clinical severity was accompanied by a marked reduction in inflammatory infiltrate and re-epithelization of the epithelial layer. Conclusion Eudragit L100 nanofibers (EL-NF) loaded with KET (F1) suppressed

  16. In vitro-in vivo evaluation of in situ gelling and thermosensitive ketoprofen liquid suppositories.

    Science.gov (United States)

    Ozgüney, Işık; Kardhiqi, Anita; Yıldız, Gülbeyaz; Ertan, Gökhan

    2014-12-01

    The main objective of this study was to investigate the release and pharmacokinetic profiles of ketoprofen (KP) from developed thermosensitive and mucoadhesive liquid suppositories. Thermosensitive liquid suppositories were prepared using KP, poloxamer 407 (P 407), poloxamer 188 (P 188) and various amounts of different mucoadhesive polymers. In vitro release studies was monitored by the USP XXVI paddle method. The results thus obtained were evaluated kinetically and mechanism of release was analyzed. Identification of poloxamer gel localization in vivo was conducted using white male rabbits by adding 1 % methylene blue. For in vivo studies, twenty-four white male rabbits were randomly divided into three groups. The rabbits in each group were administered with liquid suppository F1 [P407/P188/KP (4/20/2.5 %)], F5 [P407/P188/KP/C (4/20/2.5/0.8 %)] or conventional suppository (F-C) into the rectum. The plasma concentration of KP was analyzed by high performance liquid chromatography (HPLC). C max, AUC, MRT and T max were evaluated. The release of KP was variously affected by the mucoadhesive polymers. In vitro release studies showed that Carbopol 934 P(C) has significant effect on release rate among the mucoadhesive polymers. When the formulations were evaluated kinetically, different kinetic models were obtained. Formulation F6 [P407/P188/KP/C (4/20/2.5/1.6 %)] which contains the highest C concentration and very high viscosity, shows a significantly better fit with Higuchi kinetic model. n value of this formulation was also found approximately 0.5. n exponent results of the other formulations showed that KP might be released from the suppositories by non-Fickian diffusion. Identification of poloxamer gel localization in vivo showed that the suppositories remain in the rectum without leakage after administration. With regard to the results of in vivo studies, the AUC6→14 values of KP in liquid suppository containing C are significantly higher than those in

  17. Surrogate motherhood as a medical treatment procedure for women's infertility.

    Science.gov (United States)

    Jovic, Olga S

    2011-03-01

    The content of this work is conceived on the research of the consequences of surrogate motherhood as a process of assisted procreation, which represent a way of parenthood in cases when it is not possible to realize parenthood through a natural way. Surrogate motherhood is a process in which a woman (surrogate mother) agrees to carry a pregnancy with the intent to give the child to the couple with whom she has made a contract on surrogate maternity after the birth. This process of conception and birth makes the determination of the child's origin on its mother's side hard to determine, because of the distinction of the genetic and gestation phases of the two women. The concept of surrogate motherhood is to appear in two forms, depending on the existence or the non-existence of the genetic link between the surrogate mother and the child she gives birth to. There are gestation (full) and genetic (partial) surrogates each with different modalities and legal and ethical implications. In Serbia, Infertility Treatment and the Bio-medically Assisted Procreation Act from 2009 explicitly forbids surrogate motherhood, despite the fact that an infertile couple decides to use it, as a rule, after having tried all other treatment procedures, in cases when there is a diagnosis but the conventional treatment applied has not produced the desired results. Given the fact that no one has the right to ignore the sufferings of people who cannot procreate naturally, the medical practice and legal science in our country plead for a formulation of a legal framework in which to apply surrogate motherhood as an infertility treatment, under particular conditions.

  18. Interconversion of ketoprofen recognition in firefly luciferase-catalyzed enantioselective thioesterification reaction using from Pylocoeria miyako (PmL) and Hotaria parvura (HpL) just by mutating two amino acid residues.

    Science.gov (United States)

    Kato, Dai-ichiro; Hiraishi, Yoshihiro; Maenaka, Mika; Yokoyama, Keisuke; Niwa, Kazuki; Ohmiya, Yoshihiro; Takeo, Masahiro; Negoro, Seiji

    2013-11-01

    We identified the critical amino acid residues for substrate recognition using two firefly luciferases from Pylocoeria miyako (PmL) and Hotaria parvura (HpL), as these two luciferase enzymes exhibit different activities toward ketoprofen. Specifically, PmL can catalyze the apparent enantioselective thioesterification reaction, while HpL cannot. By comparing the amino acid sequences around the active site, we identified two residues (I350 and M397 in PmL and F351 and S398 in HpL) that were different between the two enzymes, and the replacement of these amino acids resulted in changing the ketoprofen recognition pattern. The inactive HpL was converted to the active enzyme toward ketoprofen and vice versa for PmL. These residues also affected the enantioselectivity toward ketoprofen; however, the bioluminescent color was not affected. In addition, using molecular dynamics calculations, the replacement of these two amino acids induced changes in the state of hydrogen bonding between ketoprofen and the S349 side chain through the active site water. As S349 is not considered to influence color tuning, these changes specifically caused the differences in ketoprofen recognition in the enzyme.

  19. Mother-daughter in vitro fertilization triplet surrogate pregnancy.

    Science.gov (United States)

    Michelow, M C; Bernstein, J; Jacobson, M J; McLoughlin, J L; Rubenstein, D; Hacking, A I; Preddy, S; Van der Wat, I J

    1988-02-01

    A successful triplet pregnancy has been established in a surrogate gestational mother following the transfer of five embryos fertilized in vitro. The oocytes were donated by her biological daughter, and the sperm obtained from the daughter's husband. The daughter's infertility followed a total abdominal hysterectomy performed for a postpartum hemorrhage as a result of a placenta accreta. Synchronization of both their menstrual cycles was obtained using oral contraceptive suppression for 2 months, followed by stimulation of both the surrogate gestational mother and her daughter such that embryo transfer would occur at least 48 hr after the surrogate gestational mother's own ovulation. This case raises a number of medical, social, psychological, and ethical issues.

  20. SURROGATE MOTHER DALAM PERSPEKTIF HUKUM PIDANA INDONESIA

    Directory of Open Access Journals (Sweden)

    Mr. Muntaha

    2013-04-01

    Full Text Available The development of science and technology, in particular in the field of health, has already recently brought a huge advantage and problem in human life. An example of technological marvel that not only requires deep legal thoughts but also at the same time solution is the bio-medical technology advancement of surrogacy. Surrogacy deals with human’s inclination towards reproductive activity. However, it opens up legal complication, in particular with regards to the potential commission of a criminal action as well as to the notion of doctor’s liability. Perkembangan ilmu dan teknologi di bidang kesehatan yang semakin maju dan pesat telah membawa berbagai manfaat dan masalah dalam kehidupan manusia dewasa ini. Salah satu perkembangan yang tidak hanya membutuhkan pemikiran di bidang hukum, tetapi juga sekaligus solusinya adalah mengenai kecanggihan teknologi bio-medis surrogate mother. Surrogacy menyentuh sisi kemanusiaan seorang insan terhadap reproduksi. Akan tetapi, lembaga surrogacy juga membawa komplikasi hukum terutama terkait dengan potensi tindak pidana dan dengan persoalan tanggung jawab dokter.

  1. Polynomial Chaos Surrogates for Bayesian Inference

    KAUST Repository

    Le Maitre, Olivier

    2016-01-06

    The Bayesian inference is a popular probabilistic method to solve inverse problems, such as the identification of field parameter in a PDE model. The inference rely on the Bayes rule to update the prior density of the sought field, from observations, and derive its posterior distribution. In most cases the posterior distribution has no explicit form and has to be sampled, for instance using a Markov-Chain Monte Carlo method. In practice the prior field parameter is decomposed and truncated (e.g. by means of Karhunen- Lo´eve decomposition) to recast the inference problem into the inference of a finite number of coordinates. Although proved effective in many situations, the Bayesian inference as sketched above faces several difficulties requiring improvements. First, sampling the posterior can be a extremely costly task as it requires multiple resolutions of the PDE model for different values of the field parameter. Second, when the observations are not very much informative, the inferred parameter field can highly depends on its prior which can be somehow arbitrary. These issues have motivated the introduction of reduced modeling or surrogates for the (approximate) determination of the parametrized PDE solution and hyperparameters in the description of the prior field. Our contribution focuses on recent developments in these two directions: the acceleration of the posterior sampling by means of Polynomial Chaos expansions and the efficient treatment of parametrized covariance functions for the prior field. We also discuss the possibility of making such approach adaptive to further improve its efficiency.

  2. A Large-Scale Study of Surrogate Physicality and Gesturing on Human–Surrogate Interactions in a Public Space

    Directory of Open Access Journals (Sweden)

    Kangsoo Kim

    2017-07-01

    Full Text Available Technological human surrogates, including robotic and virtual humans, have been popularly used in various scenarios, including training, education, and entertainment. Prior research has investigated the effects of the surrogate’s physicality and gesturing in human perceptions and social influence of the surrogate. However, those studies have been carried out in research laboratories, where the participants were aware that it was an experiment, and the participant demographics are typically relatively narrow—e.g., college students. In this paper, we describe and share results from a large-scale exploratory user study involving 7,685 people in a public space, where they were unaware of the experimental nature of the setting, to investigate the effects of surrogate physicality and gesturing on their behavior during human–surrogate interactions. We evaluate human behaviors using several variables, such as proactivity and reactivity, and proximity. We have identified several interesting phenomena that could lead to hypotheses developed as part of future hypothesis-based studies. Based on the measurements of the variables, we believe people are more likely to be engaged in a human–surrogate interaction when the surrogate is physically present, but movements and gesturing with its body parts have not shown the expected benefits for the interaction engagement. Regarding the demographics of the people in the study, we found higher overall engagement for females than males, and higher reactivity for younger than older people. We discuss implications for practitioners aiming to design a technological surrogate that will directly interact with real humans.

  3. Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints

    Science.gov (United States)

    Cacao, Eliedonna; Hada, Megumi; Saganti, Premkumar B.; George, Kerry A.; Cucinotta, Francis A.

    2016-01-01

    The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE) factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE’s using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE’s are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (10) are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE’s against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed. PMID:27111667

  4. Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints.

    Directory of Open Access Journals (Sweden)

    Eliedonna Cacao

    Full Text Available The biological effects of high charge and energy (HZE particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE's using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE's are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (10 are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE's against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed.

  5. Analysis of flurbiprofen, ketoprofen and etodolac enantiomers by pre-column derivatization RP-HPLC and application to drug-protein binding in human plasma.

    Science.gov (United States)

    Jin, Yin-Xiu; Tang, Yi-Hong; Zeng, Su

    2008-04-14

    A stereoselective reversed-phase high-performance liquid chromatography (HPLC) assay to determine the enantiomers of flurbiprofen, ketoprofen and etodolac in human plasma was developed. Chiral drug enantiomers were extracted from human plasma with liquid-liquid extraction. Then flurbiprofen and ketoprofen enantiomers reacted with the acylation reagent thionyl chloride and pre-column chiral derivatization reagent (S)-(-)-alpha-(1-naphthyl)ethylamine (S-NEA), and etodolac enantiomers reacted with S-NEA using 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide (EDC) and 1-hydroxybenzotriazole (HOBT) as coupling agents. The derivatized products were separated on an Agilent Zorbax C18 (4.6 mm x 250 mm, 5 microm) column with a mixture of acetonitrile-0.01 mol.L(-1) phosphate buffer (pH 4.5) (70:30, v/v) for flurbiprofen enantiomers, acetonitrile-0.01 mol.L(-1) phosphate buffer (pH 4.5) (60:40, v/v) for ketoprofen enantiomers and methonal-0.01 mol.L(-1) potassium dihydrogen phosphate buffer (pH 4.5) (88:12, v/v) for etodolac enantiomers as mobile phase. The flow of mobile phase was set at 0.8 mL.min(-1) and the detection wavelength of UV detector was set at 250 nm for flurbiprofen and ketoprofen enantiomers and 278 nm for etodolac enantiomers. The assay was linear from 0.5 to 50 microg.mL(-1) for each enantiomer. The inter- and intra-day precision (R.S.D.) was less than 10% and the average extraction recovery was more than 87% for each enantiomer. The limit of quantification for the method was 0.5 microg.mL(-1) (R.S.D.<10%, n=5). The method developed was used to study the drug-protein binding of flurbiprofen, ketoprofen and etodolac enantiomers in human plasma. The results showed that the stereoselective binding of etodolac enantiomer was observed and flurbiprofen and ketoprofen enantiomers were not.

  6. The influence of guaifenesin and ketoprofen on the properties of hot-melt extruded polyethylene oxide films.

    Science.gov (United States)

    Crowley, Michael M; Fredersdorf, Anke; Schroeder, Britta; Kucera, Shawn; Prodduturi, Suneela; Repka, Michael A; McGinity, James W

    2004-08-01

    Films containing polyethylene oxide (PEO) and a model drug, either guaifenesin (GFN) or ketoprofen (KTP), were prepared by hot-melt extrusion. The thermal properties of the hot-melt extruded films were investigated using differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) was used to examine the surface morphology of the films, and wide angle X-ray diffraction (XRD) was used to investigate the crystalline properties of the polymer, drugs and physical mixtures as well as the solid state structure of the films. The stability of the polymer was studied using gel permeation chromatography. The mechanical properties, including percent elongation and tensile strength of the films, were determined on an Instron according to American Society for Testing Materials (ASTM) procedures. The Hansen solubility parameter was calculated using the Hoftyzer or van Krevelen method to estimate the likelihood of drug--polymer miscibility. Both GFN and KTP were stable during the extrusion process. Melting points corresponding to the crystalline drugs were not observed in the films. Crystallization of GFN on the surface of the film was observed at all concentrations studied, however KTP crystallization did not occur until reaching the 15% level. Guaifenesin and ketoprofen were found to decrease drive load, increase PEO stability and plasticize the polymer during extrusion. The Hansen solubility parameters predicted miscibility between PEO and KTP and poor miscibility between PEO and GFN. The predictions of the solubility parameters were in agreement with the XRD and SEM results. The percent elongation decreased with increasing GFN concentrations and significantly increased with increasing levels of KTP. Both GFN and KTP decreased the tensile strength of the extruded film.

  7. Hepatology may have problems with putative surrogate outcome measures

    DEFF Research Database (Denmark)

    Gluud, Christian; Brok, Jesper; Gong, Yan;

    2007-01-01

    hepatitis C, serum bilirubin concentration following ursodeoxycholic acid or immunosuppressants for patients with primary biliary cirrhosis, and nutritional outcomes following artificial nutrition for liver patients may not be valid surrogates for morbidity or mortality. The challenge is to develop reliable...

  8. Fernald Silos 1 & 2 Accelerated Waste Retrieval Program Surrogate Development

    Energy Technology Data Exchange (ETDEWEB)

    Mullen, O Dennis; Erian, Fadel F.

    2002-09-01

    Whitepaper describing the rationale and methodology for development of surrogates to be used for testing retrieval and processing systems for the DOE Fernald Silos 1 & 2 wastes. One significant updating/revision is expected.

  9. THE SURROGATE COLONIZATION OF PALESTINE, 1917-1939

    OpenAIRE

    Atran, Scott

    1989-01-01

    The "surrogate colonization" of Palestine had a foreign power giving to a nonnative group rights over land occupied by an indigenous people. It thus brought into play the complementary and conflicting agendas of three culturally distinguishable parties: British, Jews and Arabs. Each party had both "externalist" [those with no sustained practical experience of day to day life in Palestine] and "internalist" representatives. The surrogate idea was based on a "strategic consensus" involving each...

  10. Surrogate nutrition markers, malnutrition, and adequacy of nutrition support.

    Science.gov (United States)

    Seres, David S

    2005-06-01

    Surrogate nutrition markers are used to assess adequacy of nourishment and to define malnutrition despite evidence that fails to link nourishment, surrogate markers, and outcomes. Markers such as serum levels of albumin, prealbumin, transferrin, and IGF-1 and delayed hypersensitivity and total lymphocyte count may be valid to help stratify risk. However, it is not appropriate to consider these as markers of adequacy of nourishment in the sick patient.

  11. Emotional experiences in surrogate mothers: A qualitative study

    OpenAIRE

    Hoda Ahmari Tehran; Shohreh Tashi; Nahid Mehran; Narges Eskandari; Tahmineh Dadkhah Tehrani

    2014-01-01

    Background: Surrogacy is one of the new techniques of assisted reproduction technology in which a woman carries and bears a child for another woman. In Iran, many Shia clerics and jurists considered it permissible so there is no religious prohibition for it. In addition to the risk of physical complications for complete surrogate mothers, the possibility of psychological complications resulted from emotional attachment to a living creature in the surrogate mother as another injury requires co...

  12. Human surrogate models of neuropathic pain: validity and limitations.

    Science.gov (United States)

    Binder, Andreas

    2016-02-01

    Human surrogate models of neuropathic pain in healthy subjects are used to study symptoms, signs, and the hypothesized underlying mechanisms. Although different models are available, different spontaneous and evoked symptoms and signs are inducible; 2 key questions need to be answered: are human surrogate models conceptually valid, ie, do they share the sensory phenotype of neuropathic pain states, and are they sufficiently reliable to allow consistent translational research?

  13. Magnetometer Response of Commonly Found Munitions Items and Munitions Surrogates

    Science.gov (United States)

    2012-01-12

    Predicted minimum magnetometer anomaly strength for a variety of munitions and surrogate items at a burial depth corresponding to 11x their respective...Response Live Site Demonstrations. The authors would like to thank Craig Murray of Parsons and Stephen Billings of Sky Research for their...variety of munitions and surrogate items at a burial depth corresponding to 11x their respective diameter. The sensor is assumed to be deployed as part

  14. Financial Surrogate Decision Making: Lessons from Applied Experimental Philosophy.

    Science.gov (United States)

    Feltz, Adam

    2016-09-20

    An estimated 1 in 4 elderly Americans need a surrogate to make decisions at least once in their lives. With an aging population, that number is almost certainly going to increase. This paper focuses on financial surrogate decision making. To illustrate some of the empirical and moral implications associated with financial surrogate decision making, two experiments suggest that default choice settings can predictably influence some surrogate financial decision making. Experiment 1 suggested that when making hypothetical financial decisions, surrogates tended to stay with default settings (OR = 4.37, 95% CI 1.52, 12.48). Experiment 2 replicated and extended this finding suggesting that in a different context (OR = 2.27, 95% CI 1.1, 4.65). Experiment 2 also suggested that those who were more numerate were less likely to be influenced by default settings than the less numerate, but only when the decision is whether to "opt in" (p = .05). These data highlight the importance of a recent debate about "nudging." Defaults are common methods to nudge people to make desirable choices while allowing the liberty to choose otherwise. Some of the ethics of using default settings to nudge surrogate decision makers are discussed.

  15. Reliability-based design optimization with progressive surrogate models

    Science.gov (United States)

    Kanakasabai, Pugazhendhi; Dhingra, Anoop K.

    2014-12-01

    Reliability-based design optimization (RBDO) has traditionally been solved as a nested (bilevel) optimization problem, which is a computationally expensive approach. Unilevel and decoupled approaches for solving the RBDO problem have also been suggested in the past to improve the computational efficiency. However, these approaches also require a large number of response evaluations during optimization. To alleviate the computational burden, surrogate models have been used for reliability evaluation. These approaches involve construction of surrogate models for the reliability computation at each point visited by the optimizer in the design variable space. In this article, a novel approach to solving the RBDO problem is proposed based on a progressive sensitivity surrogate model. The sensitivity surrogate models are built in the design variable space outside the optimization loop using the kriging method or the moving least squares (MLS) method based on sample points generated from low-discrepancy sampling (LDS) to estimate the most probable point of failure (MPP). During the iterative deterministic optimization, the MPP is estimated from the surrogate model for each design point visited by the optimizer. The surrogate sensitivity model is also progressively updated for each new iteration of deterministic optimization by adding new points and their responses. Four example problems are presented showing the relative merits of the kriging and MLS approaches and the overall accuracy and improved efficiency of the proposed approach.

  16. Integrating sol-gel with cold plasmas modified porous polycaprolactone membranes for the drug-release of silver-sulfadiazine and ketoprofen

    Science.gov (United States)

    Mangindaan, Dave; Chen, Chao-Ting; Wang, Meng-Jiy

    2012-12-01

    A controlled release system composed of surface modified porous polycaprolactone (PCL) membranes combined with a layer of tetraorthosilicate (TEOS)-chitosan sol-gel was reported in this study. PCL is a hydrophobic, semi-crystalline, and biodegradable polymer with a relatively slow degradation rate. The drugs chosen for release experiments were silver-sulfadiazine (AgSD) and ketoprofen which were impregnated in the TEOS-chitosan sol-gel. The surface modification was achieved by O2 plasma and the surfaces were characterized by water contact angle (WCA) measurements, atomic force microscope (AFM), scanning electron microscope and electron spectroscopy for chemical analysis (ESCA). The results showed that the release of AgSD on O2 plasma treated porous PCL membranes was prolonged when compared with the pristine sample. On the contrary, the release rate of ketoprofen revealed no significant difference on pristine and plasma treated PCL membranes. The prepared PCL membranes showed good biocompatibility for the wound dressing biomaterial applications.

  17. A surrogate-based metaheuristic global search method for beam angle selection in radiation treatment planning

    Science.gov (United States)

    Zhang, H. H.; Gao, S.; Chen, W.; Shi, L.; D'Souza, W. D.; Meyer, R. R.

    2013-03-01

    An important element of radiation treatment planning for cancer therapy is the selection of beam angles (out of all possible coplanar and non-coplanar angles in relation to the patient) in order to maximize the delivery of radiation to the tumor site and minimize radiation damage to nearby organs-at-risk. This category of combinatorial optimization problem is particularly difficult because direct evaluation of the quality of treatment corresponding to any proposed selection of beams requires the solution of a large-scale dose optimization problem involving many thousands of variables that represent doses delivered to volume elements (voxels) in the patient. However, if the quality of angle sets can be accurately estimated without expensive computation, a large number of angle sets can be considered, increasing the likelihood of identifying a very high quality set. Using a computationally efficient surrogate beam set evaluation procedure based on single-beam data extracted from plans employing equally-spaced beams (eplans), we have developed a global search metaheuristic process based on the nested partitions framework for this combinatorial optimization problem. The surrogate scoring mechanism allows us to assess thousands of beam set samples within a clinically acceptable time frame. Tests on difficult clinical cases demonstrate that the beam sets obtained via our method are of superior quality.

  18. In Situ Formed Phase Transited Drug Delivery System of Ketoprofen for Achieving Osmotic, Controlled and Level A In Vitro In Vivo Correlation

    OpenAIRE

    2008-01-01

    A dry process induced phase transited, non disintegrating, controlled release, in situ formed asymmetric membrane capsular system for poorly water soluble drug, ketoprofen, was developed and evaluated both in vitro and in vivo for osmotic and controlled release of the drug. In situ formed asymmetric membrane capsules were prepared using fabricated glass capsule holders via dry, phase inversion process. Effect of varying osmotic pressure of the dissolution medium on drug release was studied. M...

  19. Improved enantioselectivity of thermostable esterase from Archaeoglobus fulgidus toward (S)-ketoprofen ethyl ester by directed evolution and characterization of mutant esterases.

    Science.gov (United States)

    Kim, Jinyeong; Kim, Seungbum; Yoon, Sangyoung; Hong, Eunsoo; Ryu, Yeonwoo

    2015-08-01

    Thermostable esterases have potential applications in various biotechnology industries because of their resistance to high temperature and organic solvents. In a previous study, we isolated an esterase from Archaeoglobus fulgidus DSM 4304 (Est-AF), which showed high thermostability but low enantioselectivity toward (S)-ketoprofen ethyl ester. (R)-ketoprofenor (S)-ketoprofenis produced by esterase hydrolysis of the ester bond of (R,S)-ketoprofen ethyl ester and (S)-ketoprofen has better pharmaceutical activity and lower side effects than (R)-ketoprofen. Therefore, we have generated mutants of Est-AF that retained high thermostability whilst improving enantioselectivity. A library of Est-AF mutants was created by error-prone polymerase chain reaction, and mutants with improved enantioselectivity were isolated by site-saturation mutagenesis. The regions of Est-AF containing amino acid mutations were analyzed by homology modeling of its three-dimensional structure, and structure-based explanations for the changes in enantioselectivity are proposed. Finally, we isolated two mutants showing improved enantioselectivity over Est-AF (ee% = -16.2 ± 0.2 and E = 0.7 ± 0.0): V138G (ee% = 35.9 ± 1.0 and E = 3.0 ± 0.1) and V138G/L200R (ee% = 89.2 ± 0.2 and E = 19.5 ± 0.5). We also investigated various characteristics of these mutants and found that the mutants showed similar thermostability and resistance to additives or organic solvents to Est-AF, without a significant trade-off between activity and stability.

  20. Beyond multi-fractals: surrogate time series and fields

    Science.gov (United States)

    Venema, V.; Simmer, C.

    2007-12-01

    Most natural complex are characterised by variability on a large range of temporal and spatial scales. The two main methodologies to generate such structures are Fourier/FARIMA based algorithms and multifractal methods. The former is restricted to Gaussian data, whereas the latter requires the structure to be self-similar. This work will present so-called surrogate data as an alternative that works with any (empirical) distribution and power spectrum. The best-known surrogate algorithm is the iterative amplitude adjusted Fourier transform (IAAFT) algorithm. We have studied six different geophysical time series (two clouds, runoff of a small and a large river, temperature and rain) and their surrogates. The power spectra and consequently the 2nd order structure functions were replicated accurately. Even the fourth order structure function was more accurately reproduced by the surrogates as would be possible by a fractal method, because the measured structure deviated too strong from fractal scaling. Only in case of the daily rain sums a fractal method could have been more accurate. Just as Fourier and multifractal methods, the current surrogates are not able to model the asymmetric increment distributions observed for runoff, i.e., they cannot reproduce nonlinear dynamical processes that are asymmetric in time. Furthermore, we have found differences for the structure functions on small scales. Surrogate methods are especially valuable for empirical studies, because the time series and fields that are generated are able to mimic measured variables accurately. Our main application is radiative transfer through structured clouds. Like many geophysical fields, clouds can only be sampled sparsely, e.g. with in-situ airborne instruments. However, for radiative transfer calculations we need full 3-dimensional cloud fields. A first study relating the measured properties of the cloud droplets and the radiative properties of the cloud field by generating surrogate cloud

  1. Integrating sol-gel with cold plasmas modified porous polycaprolactone membranes for the drug-release of silver-sulfadiazine and ketoprofen

    Energy Technology Data Exchange (ETDEWEB)

    Mangindaan, Dave; Chen, Chao-Ting [Department of Chemical Engineering, National Taiwan University of Science and Technology, 43, Keelung Rd., Sec. 4, Taipei 106, Taiwan (China); Wang, Meng-Jiy, E-mail: mjwang@mail.ntust.edu.tw [Department of Chemical Engineering, National Taiwan University of Science and Technology, 43, Keelung Rd., Sec. 4, Taipei 106, Taiwan (China)

    2012-12-01

    Highlights: Black-Right-Pointing-Pointer Integrated control-release system of sol-gel and biodegradable polycaprolactone membrane. Black-Right-Pointing-Pointer Biocompatible and nontoxic chitosan-SiO{sub 2} sol-gel for drug loading. Black-Right-Pointing-Pointer Characterizations of the oxygen plasma modified biodegradable PCL porous membrane. Black-Right-Pointing-Pointer Achieved controllable in vitro release for ketoprofen and silver sulfadiazine. Black-Right-Pointing-Pointer The sol-gel/plasma modified porous membranes showed excellent biocompatibility. - Abstract: A controlled release system composed of surface modified porous polycaprolactone (PCL) membranes combined with a layer of tetraorthosilicate (TEOS)-chitosan sol-gel was reported in this study. PCL is a hydrophobic, semi-crystalline, and biodegradable polymer with a relatively slow degradation rate. The drugs chosen for release experiments were silver-sulfadiazine (AgSD) and ketoprofen which were impregnated in the TEOS-chitosan sol-gel. The surface modification was achieved by O{sub 2} plasma and the surfaces were characterized by water contact angle (WCA) measurements, atomic force microscope (AFM), scanning electron microscope and electron spectroscopy for chemical analysis (ESCA). The results showed that the release of AgSD on O{sub 2} plasma treated porous PCL membranes was prolonged when compared with the pristine sample. On the contrary, the release rate of ketoprofen revealed no significant difference on pristine and plasma treated PCL membranes. The prepared PCL membranes showed good biocompatibility for the wound dressing biomaterial applications.

  2. Indoor radon, geogenic radon surrogates and geology - Investigations on their correlation.

    Science.gov (United States)

    Friedmann, H; Baumgartner, A; Bernreiter, M; Gräser, J; Gruber, V; Kabrt, F; Kaineder, H; Maringer, F J; Ringer, W; Seidel, C; Wurm, G

    2017-01-01

    The indoor radon concentration was measured in most houses in a couple of municipalities in Austria. At the same time the activity concentration of radium in soil, the soil gas radon concentration, the permeability of the ground and the ambient dose equivalent rate were also measured and the geological situations (geological units) were recorded too. From the indoor radon concentration and different house and living parameters a radon potential (Austrian radon potential) was derived which should represent the radon concentration in a standard room. Another radon potential (Neznal radon potential) was calculated from the soil gas radon concentration and the permeability. The aim of the investigation was to correlate all the different variables and to test if the use of surrogate data (e.g. geological information, ambient dose equivalent rate, etc.) can be used to judge the radon risk for an area without performing numerous indoor measurements.

  3. Surrogate Modeling of Deformable Joint Contact using Artificial Neural Networks

    Science.gov (United States)

    Eskinazi, Ilan; Fregly, Benjamin J.

    2016-01-01

    Deformable joint contact models can be used to estimate loading conditions for cartilage-cartilage, implant-implant, human-orthotic, and foot-ground interactions. However, contact evaluations are often so expensive computationally that they can be prohibitive for simulations or optimizations requiring thousands or even millions of contact evaluations. To overcome this limitation, we developed a novel surrogate contact modeling method based on artificial neural networks (ANNs). The method uses special sampling techniques to gather input-output data points from an original (slow) contact model in multiple domains of input space, where each domain represents a different physical situation likely to be encountered. For each contact force and torque output by the original contact model, a multi-layer feed-forward ANN is defined, trained, and incorporated into a surrogate contact model. As an evaluation problem, we created an ANN-based surrogate contact model of an artificial tibiofemoral joint using over 75,000 evaluations of a fine-grid elastic foundation (EF) contact model. The surrogate contact model computed contact forces and torques about 1000 times faster than a less accurate coarse grid EF contact model. Furthermore, the surrogate contact model was seven times more accurate than the coarse grid EF contact model within the input domain of a walking motion. For larger input domains, the surrogate contact model showed the expected trend of increasing error with increasing domain size. In addition, the surrogate contact model was able to identify out-of-contact situations with high accuracy. Computational contact models created using our proposed ANN approach may remove an important computational bottleneck from musculoskeletal simulations or optimizations incorporating deformable joint contact models. PMID:26220591

  4. Biodegradation of naphthenic acid surrogates by axenic cultures.

    Science.gov (United States)

    Yue, Siqing; Ramsay, Bruce A; Ramsay, Juliana A

    2015-07-01

    This is the first study to report that bacteria from the genera Ochrobactrum, Brevundimonas and Bacillus can be isolated by growth on naphthenic acids (NAs) extracted from oil sands process water (OSPW). These pure cultures were screened for their ability to use a range of aliphatic, cyclic and aromatic NA surrogates in 96-well microtiter plates using water-soluble tetrazolium redox dyes (Biolog Redox Dye H) as the indicator of metabolic activity. Of the three cultures, Ochrobactrum showed most metabolic activity on the widest range of NA surrogates. Brevundomonas and especially Ochrobactrum had higher metabolic activity on polycyclic aromatic compounds than other classes of NA surrogates. Bacillus also oxidized a wide range of NA surrogates but not as well as Ochrobactrum. Using this method to characterize NA utilisation, one can identify which NAs or NA classes in OSPW are more readily degraded. Since aromatic NAs have been shown to have an estrogenic effect and polycyclic monoaromatic compounds have been suggested to pose the greatest environmental threat among the NAs, these bacterial genera may play an important role in detoxification of OSPW. Furthermore, this study demonstrates that bacteria belonging to the genera Ochrobactrum and Bacillus can also degrade surrogates of tricyclic NAs.

  5. Searching for Dynamical Earthquake Precursors with Surrogate Data

    Science.gov (United States)

    Lynch, J.; Revenaugh, J.; Georgopoulos, A.

    2007-12-01

    Surrogate data methods are resampling techniques related to the modern statistical bootstrap. The nonlinear dynamics community has promoted surrogate data as a useful tool for establishing the presence of nonlinear dynamics in experimental observations before applying more specific techniques such as nonlinear prediction. We propose to use surrogate data tests to search for evidence of transient nonlinear dynamics in seismographic data that act as a proxy for earthquake triggering mechanisms, such as fluid flow in the fault zone, failure cascades and slow prefatory slip, that signal changes in the coupling between geological boundaries. We will analyze the vertical component of broadband seismographic data recorded at 20Hz by the CI network of approximately 100 stations located throughout Southern California. We will focus on a period of six hours prior to seismic events of magnitude 4-5 located inside the CI network. Each seismographic record will be scanned for short, non-overlapping segments that pass a moderate stationarity criterion. We will then apply surrogate tests to each qualifying segment using three discriminating statistics: time reversal asymmetry, delay vector variance and zeroth-order nonlinear prediction error. We will correlate the results with known seismic activity and examine the spatial and temporal distribution of the surrogate test results for potential dynamical earthquake precursors.

  6. On the application of an environmental radiological assessment system to an anthropomorphic surrogate.

    Science.gov (United States)

    Brown, Justin E; Hosseini, Ali; Dowdall, Mark

    2014-01-01

    Recent developments have seen the expansion of the system of radiological protection for humans to one including protection of the environment against detrimental effects of radiation exposure, although a fully developed framework for integration of human and ecological risk assessment for radionuclides is only at an early stage. In the context of integration, significant differences exist between assessment methodologies for humans and the environment in terms of transfer, exposure, and dosimetry. The aim of this elaboration was to explore possible implications of the simplifications made within the system of environmental radiological protection in terms of the efficacy and robustness of dose-rate predictions. A comparison was conducted between human radiological assessment and environmental radiological assessment for an anthropomorphic surrogate, the results for which, produced by both the environmental and human-oriented risk assessment systems, were critically compared and contrasted. The adopted approach split the calculations into several parts, these being 1) physical transfer in an ecosystem, 2) transfer to humans, 3) internal doses to humans, and 4) external doses to humans. The calculations were carried out using both a human radiological assessment and ecological risk assessment system for the same surrogate. The results of this comparison provided indications as to where the 2 systems are amenable to possible integration and where such integration may prove difficult. Initial stage transport models seem to be an obvious component amenable for integration, although complete integration is arguably unattainable as the differences between endpoints mean that the relevant outputs from the models will not be the same. For the transfer and dosimetry components of 2 typical methodologies, it seems that the efficacy of the environmental system is radionuclide-dependent, the predictions given by the environmental system for (90) Sr and (60) Co being

  7. Percutaneous Absorption and Metabolism of Ketoprofen Isopropyl Ester via Excised Nude Mouse‘s and Monkey’s Skin

    Institute of Scientific and Technical Information of China (English)

    ZHUQuan-gang; HUJin-hong

    2003-01-01

    Aim:To study percutaneous absorption and metabolism of ketoprofen isopropyl ester (KPE)via excised nude mouse's and monkey's skin.Methods:Excised skin was prepared by surgical excision and enzyme digestion.Sideby-side diffusion cells were used for in vitro permeation studies.The concentrations of KPE and its metabolite in samples were assayed by HPLC.Results:All KPE penetration through whole thickness skin and stripped skin was metabolized to ketoprofen(KP).the concentration of which in the reciiver solution increased linearly with time.As to the nude mouse skin.the steady-state flux of KP through whole thickness skin was 2.5 times that of KPE through the whloe thickness skin,but the KP and KPE remaining in the whole thickness skin after the finishing of KPE penetration was 22.2 times in compered with the KP remaining in the whole thickness skin after the finshing of KP penetration.The rate of formation of the steady state KP from KPE throught dermis was significantly lower than that of KPE through the whole thickness skin.In he monkey skin,the rate of formation of the steady-state KP from KPE through the whole thickness skin was 0.7 times that from KPE through stripped skin.The KP and KPE remaining in the whole thickness skin after the finishing of KPE penetration was 2.0 time that in the stripped skin after the finishing of KPE penetration.The rate of fornation of the steady-state KP from KPE through dermis was lower than that from KPE through the whole thickness skin and the stripped skin.the KP remaining in dermis after the finsihing of KPE penetration was also significantly lower than the KP remaining in the whole thickness skin and the stripped skin after the finishing of KPE penetration.Conclusion:KP esters are of benefit to imporove the local action of KP.and skin esterase metabolism mainly develops in the epidermis.

  8. Love as a regulative ideal in surrogate decision making.

    Science.gov (United States)

    Stonestreet, Erica Lucast

    2014-10-01

    This discussion aims to give a normative theoretical basis for a "best judgment" model of surrogate decision making rooted in a regulative ideal of love. Currently, there are two basic models of surrogate decision making for incompetent patients: the "substituted judgment" model and the "best interests" model. The former draws on the value of autonomy and responds with respect; the latter draws on the value of welfare and responds with beneficence. It can be difficult to determine which of these two models is more appropriate for a given patient, and both approaches may seem inadequate for a surrogate who loves the patient. The proposed "best judgment" model effectively draws on the values incorporated in each of the traditional standards, but does so because these values are important to someone who loves a patient, since love responds to the patient as the specific person she is.

  9. Surrogate modeling for initial rotational stiffness of welded tubular joints

    Directory of Open Access Journals (Sweden)

    M.R. Garifullin

    2016-10-01

    Full Text Available Recently, buildings and structures erected in Russia and abroad have to comply with stringent economic requirements. Buildings should not only be reliable and safe, have a beautiful architectural design, but also meet the criteria of rationality and energy efficiency. In practice, this usually means the need for additional comparative analysis in order to determine the optimal solution to the engineering task. Usually such an analysis is time-consuming and requires huge computational efforts. In this regard, surrogate modeling can be an effective tool for solving such problems. This article provides a brief description of surrogate models and the basic techniques of their construction, describes the construction process of a surrogate model to calculate initial rotational stiffness of welded RHS joints made of high strength steel (HSS.

  10. Using a surrogate contact pair to evaluate polyethylene wear in prosthetic knee joints.

    Science.gov (United States)

    Sanders, Anthony P; Lockard, Carly A; Weisenburger, Joel N; Haider, Hani; Raeymaekers, Bart

    2016-01-01

    With recent improvements to the properties of ultra-high molecular weight polyethylene (UHMWPE) used in joint replacements, prosthetic knee and hip longevity may extend beyond two decades. However, it is difficult and costly to replicate such a long in vivo lifetime using clinically relevant in vitro wear testing approaches such as walking gait joint simulators. We advance a wear test intermediate in complexity between pin-on-disk and knee joint simulator tests. The test uses a surrogate contact pair, consisting of a surrogate femoral and tibial specimen that replicate the contact mechanics of any full-scale knee condyle contact pair. The method is implemented in a standard multi-directional pin-on-disk wear test machine, and we demonstrate its application via a two-million-cycle wear test of three different UHMWPE formulations. Further, we demonstrate the use of digital photography and image processing to accurately quantify fatigue damage based on the reduced transmission of light through a damage area in a UHMWPE specimen. The surrogate contact pairs replicate the knee condyle contact areas within -3% to +12%. The gravimetric wear test results reflect the dose of crosslinking radiation applied to the UHMWPE: 35 kGy yielded a wear rate of 7.4 mg/Mcycles, 55 kGy yielded 1.0 mg/Mcycles, and 75 kGy (applied to a 0.1% vitamin E stabilized UHMWPE) yielded 1.5 mg/Mcycles. A precursor to spalling fatigue is observed and precisely measured in the radiation-sterilized (35 kGy) and aged UHMWPE specimen. The presented techniques can be used to evaluate the high-cycle fatigue performance of arbitrary knee condyle contact pairs under design-specific contact stresses, using existing wear test machines. This makes the techniques more economical and well-suited to standardized comparative testing.

  11. Disinfection byproduct regulatory compliance surrogates and bromide-associated risk.

    Science.gov (United States)

    Kolb, Chelsea; Francis, Royce A; VanBriesen, Jeanne M

    2017-08-01

    Natural and anthropogenic factors can alter bromide concentrations in drinking water sources. Increasing source water bromide concentrations increases the formation and alters the speciation of disinfection byproducts (DBPs) formed during drinking water treatment. Brominated DBPs are more toxic than their chlorinated analogs, and thus have a greater impact on human health. However, DBPs are regulated based on the mass sum of DBPs within a given class (e.g., trihalomethanes and haloacetic acids), not based on species-specific risk or extent of bromine incorporation. The regulated surrogate measures are intended to protect against not only the species they directly represent, but also against unregulated DBPs that are not routinely measured. Surrogates that do not incorporate effects of increasing bromide may not adequately capture human health risk associated with drinking water when source water bromide is elevated. The present study analyzes trihalomethanes (THMs), measured as TTHM, with varying source water bromide concentrations, and assesses its correlation with brominated THM, TTHM risk and species-specific THM concentrations and associated risk. Alternative potential surrogates are evaluated to assess their ability to capture THM risk under different source water bromide concentration conditions. The results of the present study indicate that TTHM does not adequately capture risk of the regulated species when source water bromide concentrations are elevated, and thus would also likely be an inadequate surrogate for many unregulated brominated species. Alternative surrogate measures, including THM3 and the bromodichloromethane concentration, are more robust surrogates for species-specific THM risk at varying source water bromide concentrations. Copyright © 2017. Published by Elsevier B.V.

  12. Fast Prediction and Evaluation of Gravitational Waveforms Using Surrogate Models

    Directory of Open Access Journals (Sweden)

    Scott E. Field

    2014-07-01

    Full Text Available We propose a solution to the problem of quickly and accurately predicting gravitational waveforms within any given physical model. The method is relevant for both real-time applications and more traditional scenarios where the generation of waveforms using standard methods can be prohibitively expensive. Our approach is based on three offline steps resulting in an accurate reduced order model in both parameter and physical dimensions that can be used as a surrogate for the true or fiducial waveform family. First, a set of m parameter values is determined using a greedy algorithm from which a reduced basis representation is constructed. Second, these m parameters induce the selection of m time values for interpolating a waveform time series using an empirical interpolant that is built for the fiducial waveform family. Third, a fit in the parameter dimension is performed for the waveform’s value at each of these m times. The cost of predicting L waveform time samples for a generic parameter choice is of order O(mL+mc_{fit} online operations, where c_{fit} denotes the fitting function operation count and, typically, m≪L. The result is a compact, computationally efficient, and accurate surrogate model that retains the original physics of the fiducial waveform family while also being fast to evaluate. We generate accurate surrogate models for effective-one-body waveforms of nonspinning binary black hole coalescences with durations as long as 10^{5}M, mass ratios from 1 to 10, and for multiple spherical harmonic modes. We find that these surrogates are more than 3 orders of magnitude faster to evaluate as compared to the cost of generating effective-one-body waveforms in standard ways. Surrogate model building for other waveform families and models follows the same steps and has the same low computational online scaling cost. For expensive numerical simulations of binary black hole coalescences, we thus anticipate extremely large speedups in

  13. Optimization using surrogate models - by the space mapping technique

    DEFF Research Database (Denmark)

    Søndergaard, Jacob

    2003-01-01

    mapping surrogate has a lower approximation error for long steps. For short steps, however, the Taylor model of the expensive model is best, due to exact interpolation at the model origin. Five algorithms for space mapping optimization are presented and the numerical performance is evaluated. Three...... conditions are satisfied. So hybrid methods, combining the space mapping technique with classical optimization methods, should be used if convergence to high accuracy is wanted. Approximation abilities of the space mapping surrogate are compared with those of a Taylor model of the expensive model. The space...

  14. Optimization using surrogate models - by the space mapping technique

    DEFF Research Database (Denmark)

    Søndergaard, Jacob

    2003-01-01

    mapping surrogate has a lower approximation error for long steps. For short steps, however, the Taylor model of the expensive model is best, due to exact interpolation at the model origin. Five algorithms for space mapping optimization are presented and the numerical performance is evaluated. Three...... conditions are satisfied. So hybrid methods, combining the space mapping technique with classical optimization methods, should be used if convergence to high accuracy is wanted. Approximation abilities of the space mapping surrogate are compared with those of a Taylor model of the expensive model. The space...

  15. Optimization of preparation method for ketoprofen-loaded microspheres consisting polymeric blends using simplex lattice mixture design.

    Science.gov (United States)

    Das, Sanjoy Kumar; Khanam, Jasmina; Nanda, Arunabha

    2016-12-01

    In the present investigation, simplex lattice mixture design was applied for formulation development and optimization of a controlled release dosage form of ketoprofen microspheres consisting polymers like ethylcellulose and Eudragit(®)RL 100; when those were formed by oil-in-oil emulsion solvent evaporation method. The investigation was carried out to observe the effects of polymer amount, stirring speed and emulsifier concentration (% w/w) on percentage yield, average particle size, drug entrapment efficiency and in vitro drug release in 8h from the microspheres. Analysis of variance (ANOVA) was used to estimate the significance of the models. Based on the desirability function approach numerical optimization was carried out. Optimized formulation (KTF-O) showed close match between actual and predicted responses with desirability factor 0.811. No adverse reaction between drug and polymers were observed on the basis of Fourier transform infrared (FTIR) spectroscopy and Differential scanning calorimetric (DSC) analysis. Scanning electron microscopy (SEM) was carried out to show discreteness of microspheres (149.2±1.25μm) and their surface conditions during pre and post dissolution operations. The drug release pattern from KTF-O was best explained by Korsmeyer-Peppas and Higuchi models. The batch of optimized microspheres were found with maximum entrapment (~90%), minimum loss (~10%) and prolonged drug release for 8h (91.25%) which may be considered as favourable criteria of controlled release dosage form.

  16. Anodic oxidation of ketoprofen-An anti-inflammatory drug using boron doped diamond and platinum electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Murugananthan, M., E-mail: muruga.chem@gmail.com [National Metallurgical Laboratory Madras Centre, CSIR Madras Complex, Taramani, Chennai 600 113 (India); Latha, S.S.; Bhaskar Raju, G. [National Metallurgical Laboratory Madras Centre, CSIR Madras Complex, Taramani, Chennai 600 113 (India); Yoshihara, S. [Department of Advanced Interdisciplinary Science, Graduate School of Engineering, Utsunomiya University, 7-1-2 Yoto, Utsunomiya, Tochigi 321-8585 (Japan)

    2010-08-15

    The mineralization of ketoprofen (KP) by anodic oxidation was studied by employing boron doped diamond (BDD) and Pt electrodes. The redox behavior of KP molecule, fouling of electrodes, generation of oxygen and active chlorine species were studied by cyclic voltammetry. The effect of electrolyte, pH of aqueous medium and applied current density on the mineralization behavior of KP was also investigated. The degradation and mineralization were monitored by UV-vis spectrophotometer and total organic carbon analyzer, respectively. The results were explained in terms of in situ generation of hydroxyl radical ({center_dot}OH), peroxodisulfate (S{sub 2}O{sub 8}{sup 2-}), and active chlorine species (Cl{sub 2}, HOCl, OCl{sup -}). The physisorbed {center_dot}OH on BDD was observed to trigger the combustion of KP in to CO{sub 2} and H{sub 2}O. The poor mineralization at both BDD and Pt anodes in the presence of NaCl as supporting electrolyte was ascribed to the formation of chlorinated organic compounds which are refractory. Complete mineralization of KP molecule was achieved using Na{sub 2}SO{sub 4} as supporting electrolyte.

  17. Scope of partial least-squares regression applied to the enantiomeric composition determination of ketoprofen from strongly overlapped chromatographic profiles.

    Science.gov (United States)

    Padró, Juan M; Osorio-Grisales, Jaiver; Arancibia, Juan A; Olivieri, Alejandro C; Castells, Cecilia B

    2015-07-01

    Valuable quantitative information could be obtained from strongly overlapped chromatographic profiles of two enantiomers by using proper chemometric methods. Complete separation profiles where the peaks are fully resolved are difficult to achieve in chiral separation methods, and this becomes a particularly severe problem in case that the analyst needs to measure the chiral purity, i.e., when one of the enantiomers is present in the sample in very low concentrations. In this report, we explore the scope of a multivariate chemometric technique based on unfolded partial least-squares regression, as a mathematical tool to solve this quite frequent difficulty. This technique was applied to obtain quantitative results from partially overlapped chromatographic profiles of R- and S-ketoprofen, with different values of enantioresolution factors (from 0.81 down to less than 0.2 resolution units), and also at several different S:R enantiomeric ratios. Enantiomeric purity below 1% was determined with excellent precision even from almost completely overlapped signals. All these assays were tested on the most demanding condition, i.e., when the minor peak elutes immediately after the main peak. The results were validated using univariate calibration of completely resolved profiles and the method applied to the determination of enantiomeric purity of commercial pharmaceuticals.

  18. Photochemical reaction of 2-(3-benzoylphenyl)propionic acid (ketoprofen) with basic amino acids and dipeptides.

    Science.gov (United States)

    Suzuki, Tadashi; Shinoda, Mio; Osanai, Yohei; Isozaki, Tasuku

    2013-08-22

    Photoreaction of 2-(3-benzoylphenyl)propionic acid (ketoprofen, KP) with basic amino acids (histidine, lysine, and arginine) and dipeptides (carnosine and anserine) including a histidine moiety in phosphate buffer solution (pH 7.4) has been investigated with transient absorption spectroscopy. With UV irradiation KP(-) gave rise to a carbanion through a decarboxylation reaction, and the carbanion easily abstracted a proton from the surrounding molecule to yield a 3-ethylbenzophenone ketyl biradical (EBPH). The dipeptides as well as the basic amino acids were found to accelerate the proton transfer reaction whereas alanine and glycine had no effect on the reaction, revealing that these amino acids having a protonated side chain act as a proton donor. The formation quantum yield of EBPH was estimated to be fairly large by means of an actinometrical method with benzophenone, and the bimolecular reaction rate constant for the proton transfer between the carbanion and the protonated basic amino acids or the protonated dipeptides was successfully determined. It has become apparent that the bimolecular reaction rate constant for the proton transfer depended on the acid dissociation constant for the side chain of the amino acids for the first time. This reaction mechanism was interpreted by difference of the heat of reaction for each basic amino acid based on the thermodynamical consideration. These results strongly suggest that the side chain of the basic amino acid residue in protein should play an important role for photochemistry of KP in vivo.

  19. Inactivation of the Tulane Virus, a Novel Surrogate for the Human Norovirus

    Science.gov (United States)

    TIAN, PENG; YANG, DAVID; QUIGLEY, CHRISTINA; CHOU, MARISSA; JIANG, XI

    2014-01-01

    Human noroviruses (HuNoVs) are the major cause of nonbacterial gastroenteritis epidemics. The culturable feline calicivirus and murine norovirus have been used extensively as surrogates to study HuNoV biology, as HuNoV does not grow in vitro. Additional efforts to identify new surrogates are needed, because neither of these common surrogates are truly intestinal pathogens. The newly described Tulane virus (TV) is a typical calicivirus, it is isolated from macaque stools, is cultivable in vitro, and recognizes human histo-blood group antigens. Therefore, TV is a promising surrogate for HuNoVs. In this study, we evaluated the resistance or stability of TV under various physical and environmental conditions by measuring a 50% reduction of tissue culture infective dose (TCID50) by using a TV cell culture system. Due to the nature of this virus, it is hard to produce a high-titer stock through tissue culture. In our study, the maximal reduction in virus titers was 5 D (D = 1 log) in heat-denaturation and EtOH experiments, and 4 D in UV, chlorine, and pH-stability experiments. Therefore in this study, we defined the inactivation of TV as reaching a TCID50/ml of 0 (a 4- to 5-D reduction in TCID50, depending on the detection limit). TV was inactivated after incubation at 63°C for 5 min, incubation at 56°C for 30 min (5 D), exposure to 60 mJ/cm2 of UVC radiation (4 D), or incubation at 300 ppm of free chlorine for 10 min (4 D). TV was shown to be stable from pH 3.0 to 8.0, though an obvious reduction in virus titer was observed at pH 2.5 and 9.0, and was inactivated at pH 10.0 (4 D). TV was resistant to a low concentration of EtOH (40% or lower) but was fully inactivated (5 D) by 50 to 70% EtOH after a short exposure (20 s). In contrast, quantitative real-time PCR was unable to detect, or poorly detected, virus titer reductions between treated and untreated samples described in this study. PMID:23575140

  20. Summary of Remediated Nitrate Salt Surrogate Formulation and Testing

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Geoffrey Wayne [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Leonard, Philip [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hartline, Ernest Leon [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Tian, Hongzhao [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-05

    High Explosives Science and Technology (M-7) completed all required formulation and testing of Remediated Nitrate Salt (RNS) surrogates on April 27, 2016 as specified in PLAN-TA9-2443 Rev B, "Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing Standard Procedure", released February 16, 2016. This report summarizes the results of the work and also includes additional documentation required in that test plan. All formulation and testing was carried out according to PLAN-TA9-2443 Rev B. The work was carried out in three rounds, with the full matrix of samples formulated and tested in each round. Results from the first round of formulation and testing were documented in memorandum M7-J6-6042, " Results from First Round of Remediated Nitrate Salt Surrogate Formulation and Testing." Results from the second round of formulation and testing were documented in M7-16-6053 , "Results from the Second Round of Remediated Nitrate Salt Surrogate Formulation and Testing." Initial results from the third round were documented in M7-16-6057, "Initial Results from the Third Round of Remediated Nitrate Salt Formulation and Testing."

  1. Frequency response as a surrogate eigenvalue problem in topology optimization

    DEFF Research Database (Denmark)

    Andreassen, Erik; Ferrari, Federico; Sigmund, Ole

    2017-01-01

    This article discusses the use of frequency response surrogates for eigenvalue optimization problems in topology optimization that may be used to avoid solving the eigenvalue problem. The motivation is to avoid complications that arise from multiple eigenvalues and the computational complexity as...

  2. GENERATING SOPHISTICATED SPATIAL SURROGATES USING THE MIMS SPATIAL ALLOCATOR

    Science.gov (United States)

    The Multimedia Integrated Modeling System (MIMS) Spatial Allocator is open-source software for generating spatial surrogates for emissions modeling, changing the map projection of Shapefiles, and performing other types of spatial allocation that does not require the use of a comm...

  3. Strength Reliability Analysis of Turbine Blade Using Surrogate Models

    Directory of Open Access Journals (Sweden)

    Wei Duan

    2014-05-01

    Full Text Available There are many stochastic parameters that have an effect on the reliability of steam turbine blades performance in practical operation. In order to improve the reliability of blade design, it is necessary to take these stochastic parameters into account. In this study, a variable cross-section twisted blade is investigated and geometrical parameters, material parameters and load parameters are considered as random variables. A reliability analysis method as a combination of a Finite Element Method (FEM, a surrogate model and Monte Carlo Simulation (MCS, is applied to solve the blade reliability analysis. Based on the blade finite element parametrical model and the experimental design, two kinds of surrogate models, Polynomial Response Surface (PRS and Artificial Neural Network (ANN, are applied to construct the approximation analytical expressions between the blade responses (including maximum stress and deflection and random input variables, which act as a surrogate of finite element solver to drastically reduce the number of simulations required. Then the surrogate is used for most of the samples needed in the Monte Carlo method and the statistical parameters and cumulative distribution functions of the maximum stress and deflection are obtained by Monte Carlo simulation. Finally, the probabilistic sensitivities analysis, which combines the magnitude of the gradient and the width of the scatter range of the random input variables, is applied to evaluate how much the maximum stress and deflection of the blade are influenced by the random nature of input parameters.

  4. Recent Progress in the Development of Diesel Surrogate Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Pitz, W J

    2009-09-04

    There has been much recent progress in the area of surrogate fuels for diesel. In the last few years, experiments and modeling have been performed on higher molecular weight components of relevance to diesel fuel such as n-hexadecane (n-cetane) and 2,2,4,4,6,8,8-heptamethylnonane (iso-cetane). Chemical kinetic models have been developed for all the n-alkanes up to 16 carbon atoms. Also, there has been much experimental and modeling work on lower molecular weight surrogate components such as n-decane and do-decane which are most relevant to jet fuel surrogates, but are also relevant to diesel surrogates where simulation of the full boiling point range is desired. For the cycloalkanes, experimental work on decalin and tetralin recently has been published. For multi-component surrogate fuel mixtures, recent work on modeling of these mixtures and comparisons to real diesel fuel is reviewed. Detailed chemical kinetic models for surrogate fuels are very large in size. Significant progress also has been made in improving the mechanism reduction tools that are needed to make these large models practicable in multidimensional reacting flow simulations of diesel combustion. Nevertheless, major research gaps remain. In the case of iso-alkanes, there are experiments and modeling work on only one of relevance to diesel: iso-cetane. Also, the iso-alkanes in diesel are lightly branched and no detailed chemical kinetic models or experimental investigations are available for such compounds. More components are needed to fill out the iso-alkane boiling point range. For the aromatic class of compounds, there has been no new work for compounds in the boiling point range of diesel. Most of the new work has been on alkyl aromatics that are of the range C7 to C8, below the C10 to C20 range that is needed. For the chemical class of cycloalkanes, experiments and modeling on higher molecular weight components are warranted. Finally for multi-component surrogates needed to treat real diesel

  5. Recent Progress in the Development of Diesel Surrogate Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Pitz, W J; Mueller, C J

    2009-12-09

    There has been much recent progress in the area of surrogate fuels for diesel. In the last few years, experiments and modeling have been performed on higher molecular weight components of relevance to diesel fuel such as n-hexadecane (n-cetane) and 2,2,4,4,6,8,8-heptamethylnonane (iso-cetane). Chemical kinetic models have been developed for all the n-alkanes up to 16 carbon atoms. Also, there has been much experimental and modeling work on lower molecular weight surrogate components such as n-decane and n-dodecane that are most relevant to jet fuel surrogates, but are also relevant to diesel surrogates where simulation of the full boiling point range is desired. For two-ring compounds, experimental work on decalin and tetralin recently has been published. For multi-component surrogate fuel mixtures, recent work on modeling of these mixtures and comparisons to real diesel fuel is reviewed. Detailed chemical kinetic models for surrogate fuels are very large in size. Significant progress also has been made in improving the mechanism reduction tools that are needed to make these large models practicable in multi-dimensional reacting flow simulations of diesel combustion. Nevertheless, major research gaps remain. In the case of iso-alkanes, there are experiments and modeling work on only one of relevance to diesel: iso-cetane. Also, the iso-alkanes in diesel are lightly branched and no detailed chemical kinetic models or experimental investigations are available for such compounds. More components are needed to fill out the iso-alkane boiling point range. For the aromatic class of compounds, there has been no new work for compounds in the boiling point range of diesel. Most of the new work has been on alkyl aromatics that are of the range C7 to C8, below the C10 to C20 range that is needed. For the chemical class of cycloalkanes, experiments and modeling on higher molecular weight components are warranted. Finally for multi-component surrogates needed to treat real

  6. Development of a Human Cranial Bone Surrogate for Impact Studies.

    Science.gov (United States)

    Roberts, Jack C; Merkle, Andrew C; Carneal, Catherine M; Voo, Liming M; Johannes, Matthew S; Paulson, Jeff M; Tankard, Sara; Uy, O Manny

    2013-01-01

    In order to replicate the fracture behavior of the intact human skull under impact it becomes necessary to develop a material having the mechanical properties of cranial bone. The most important properties to replicate in a surrogate human skull were found to be the fracture toughness and tensile strength of the cranial tables as well as the bending strength of the three-layer (inner table-diplöe-outer table) architecture of the human skull. The materials selected to represent the surrogate cranial tables consisted of two different epoxy resins systems with random milled glass fiber to enhance the strength and stiffness and the materials to represent the surrogate diplöe consisted of three low density foams. Forty-one three-point bending fracture toughness tests were performed on nine material combinations. The materials that best represented the fracture toughness of cranial tables were then selected and formed into tensile samples and tested. These materials were then used with the two surrogate diplöe foam materials to create the three-layer surrogate cranial bone samples for three-point bending tests. Drop tower tests were performed on flat samples created from these materials and the fracture patterns were very similar to the linear fractures in pendulum impacts of intact human skulls, previously reported in the literature. The surrogate cranial tables had the quasi-static fracture toughness and tensile strength of 2.5 MPa√ m and 53 ± 4.9 MPa, respectively, while the same properties of human compact bone were 3.1 ± 1.8 MPa√ m and 68 ± 18 MPa, respectively. The cranial surrogate had a quasi-static bending strength of 68 ± 5.7 MPa, while that of cranial bone was 82 ± 26 MPa. This material/design is currently being used to construct spherical shell samples for drop tower and ballistic tests.

  7. Comparison of morphine, ketoprofen and Arnica montana 6x and 30x per oral transmucosal or subcutaneous route for control of postoperative pain in cats subjected to hysterectomy with bilateral salpingo-oophorectomy

    OpenAIRE

    Denise de Fátima Rodrigues; Stelio Pacca Loureiro Luna; Juliana Tabarelli Brondani; Bruno Watanabe Minto

    2016-01-01

    ABSTRACT: The postoperative analgesic effect of Arnica montana (Arnica) was compared to morphine and ketoprofen in 50 cats following hysterectomy with bilateral salpingo-oophorectomy (HSO). Cats were randomly allocated to five groups (n=10) and were treated 30 minutes before surgery and over 72 hours with 1ml of Arnica 30x per subcutaneous (SC) route (GA30SC); Arnica 30x per oral transmucosal route (P.O.) (GA30PO); Arnica 6x P.O. (GA6PO); morphine 0.1mg kg-1 SC (GM) SID or ketoprofen 2mg kg-1...

  8. Hall et al., 2016 Artificial Turf Surrogate Surface Methods Paper Data File

    Data.gov (United States)

    U.S. Environmental Protection Agency — Mercury dry deposition data quantified via static water surrogate surface (SWSS) and artificial turf surrogate surface (ATSS) collectors. This dataset is associated...

  9. Effects of castration method and frequency of intramuscular injections of ketoprofen on behavioral and physiological indicators of pain in beef cattle.

    Science.gov (United States)

    Moya, D; González, L A; Janzen, E; Caulkett, N A; Fireheller, E; Schwartzkopf-Genswein, K S

    2014-04-01

    Two experiments were conducted to determine the effect of a single or multiple intramuscular (i.m.) injection of ketoprofen and castration technique on physiological and behavioral indicators of pain in beef calves. A total of 150 bull calves (284.8 ± 22.7 kg BW) were used in both experiments, each 1 conducted as a 3 × 2 factorial design, where main factors included castration technique--no castration (CT), surgical (SU), or band (BA)--and drug administration--physiological solution (PS) or i.m. injection of ketoprofen (KP; 3 mg Anafen/kg BW) in the neck of calves. Animals were weighed weekly during the experiment to calculate ADG. Behavioral responses indicative of pain and discomfort during the castration procedure were documented using a visual analog score (VAS) by an experienced observer who was blind to the treatments. Movements of the animals in the chute during castration were quantified using a strain gauge system mounted on the head gate to evaluate the escape response of the cattle. Pens were equipped with an automated feed bunk monitoring system enabling feed intake and feeding behavior to be continuously monitored for each individual. Thermographic images of the scrotal area were evaluated 24 and 0.5 h before castration, 0.5, 1, 24, 48, and 270 h postcastration, and weekly thereafter until the end of the trial. Blood samples were obtained postcastration to evaluate changes in total white blood cell (WBC) count and neutrophil-to-lymphocyte (N:L) ratio. Saliva samples were taken 24 and 0.5 h before castration, immediately after castration, and 0.5, 1, 2, 5, 24, and 48 h and then 5, 7, and 14 d after castration to determine cortisol concentration. Scrotal temperature, VAS, total WBC, N:L ratio, salivary cortisol, mobility, and pressure exerted in the chute were greater (P ketoprofen to improve the consistency of its effects as a pain mitigation strategy after castration.

  10. Sequential optimization of strip bending process using multiquadric radial basis function surrogate models

    NARCIS (Netherlands)

    Havinga, Gosse Tjipke; van den Boogaard, Antonius H.; Klaseboer, G.

    2013-01-01

    Surrogate models are used within the sequential optimization strategy for forming processes. A sequential improvement (SI) scheme is used to refine the surrogate model in the optimal region. One of the popular surrogate modeling methods for SI is Kriging. However, the global response of Kriging mode

  11. Hydrogen Peroxide Vapor Decontamination in a Patient Room Using Feline Calicivirus and Murine Norovirus as Surrogate Markers for Human Norovirus.

    Science.gov (United States)

    Holmdahl, Torsten; Walder, Mats; Uzcátegui, Nathalie; Odenholt, Inga; Lanbeck, Peter; Medstrand, Patrik; Widell, Anders

    2016-05-01

    To determine whether hydrogen peroxide vapor (HPV) could be used to decontaminate caliciviruses from surfaces in a patient room. Feline calicivirus (FCV) and murine norovirus (MNV) were used as surrogate viability markers to mimic the noncultivable human norovirus. Cell culture supernatants of FCV and MNV were dried in triplicate 35-mm wells of 6-well plastic plates. These plates were placed in various positions in a nonoccupied patient room that was subsequently exposed to HPV. Control plates were positioned in a similar room but were never exposed to HPV. Virucidal activity was measured in cell culture by reduction in 50% tissue culture infective dose titer for FCV and by both 50% tissue culture infective dose titer and plaque reduction for MNV. Neither viable FCV nor viable MNV could be detected in the test room after HPV treatment. At least 3.65 log reduction for FCV and at least 3.67 log reduction for MNV were found by 50% tissue culture infective dose. With plaque assay, measurable reduction for MNV was at least 2.85 log units. The successful inactivation of both surrogate viruses indicates that HPV could be a useful tool for surface decontamination of a patient room contaminated by norovirus. Hence nosocomial spread to subsequent patients can be avoided.

  12. Ketoprofen mesoporous silica nanoparticles SBA-15 hard gelatin capsules: preparation and in vitro/in vivo characterization.

    Science.gov (United States)

    Abd-Elrahman, Ahmed A; El Nabarawi, Mohamed A; Hassan, Doaa H; Taha, Amal A

    2016-11-01

    SBA-15 is used to enhance the bioavailability of poorly soluble ketoprofen (KP) through stabilization of its amorphous state. Additionally, the current work provides a complete in vitro and in vivo study on preformulated KP-SBA-15 sample and formulated KP-SBA-15 in hard gelatin capsule. Loading of KP was done by a novel method called immersion-rotavapor method. KP was quantified by extraction and thermal gravimetric analysis (TGA). Characterization of the loaded SBA-15 sample was done by high resolution transmission electron microscopy (HRTEM), small angle X-ray diffraction (SAXRD), nitrogen adsorption/desorption isotherms, differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy and dissolution profiles. The loaded sample was formulated in hard gelatin capsule. The anti-inflammatory and analgesic studies were carried out on 24 adult male albino rats. TGA and extraction results showed 54.4 wt% of drug incorporated. Characterization of KP-SBA-15 sample confirmed the successful encapsulation of KP into the carrier pores in a molecular amorphous state. Additionally, loading of KP did not affect the mesoporous internal structure. During the first 5 min, the dissolution study showed very high release rates; nearly 50% of KP was released. These results were reflected on the in vivo study resulting in 82% inhibition in edema after 1 h and maximum analgesia after 30 min from the administration of the formulated sample. SBA-15 mesoporous silica nanoparticle proved to be a very promising drug delivery carrier that can be used as a facile way to enhance the bioavailability of poorly soluble drugs.

  13. The preparation and evaluation of sustained release suppositories containing ketoprofen and Eudragit RL 100 by using factorial design.

    Science.gov (United States)

    Ozgüney, I; Ozcan, I; Ertan, G; Güneri, T

    2007-01-01

    The preparation of ketoprofen (KP) sustained release (SR) suppositories was designed according to the 3(2) x 2(1) factorial design as three different KP:Eudragit RL 100 ratios (1:0.5, 1:1, 1:2), three particle sizes of prepared granules (250-500, 500-710, and 710-1000 microm) and two different PEG 400:PEG 6000 ratios (40:60, 50:50). The conventional KP suppositories were also prepared by using Witepsol H 15, Massa Estarinum B, Cremao and the mixture of PEG 400:PEG 6000. The dissolution studies of suppositories prepared were carried out according to the USP XXIII basket method in the phosphate buffer (pH = 7.2) at 50 rpm, and it was shown that the dissolution time was sustained up to 8 hours. According to the results of the factorial design, the most important independent variable on t50 and t80 was drug:polymer ratios. The log of partition coefficient of KP was determined as 1.46, showing the high affinity to the oily phase. n exponent and kinetic studies were conducted to explain diffusion mechanism, and it is understood that if the inert KP:Eudragit RL 100 ratio is increased in the particles, the Fickian difusion dominates and the best kinetic turns to Higuchi from the Hixson-Crowell. There is neither crystalline form of KP nor degradation product in the suppositories detected with the differential scanning calorimetry (DSC) studies. In addition to these studies, antiinflammatory activity of SR suppositories also determined that it was significantly extended according to the conventional suppositories.

  14. Very Short Literature Survey From Supervised Learning To Surrogate Modeling

    CERN Document Server

    Brusan, Altay

    2012-01-01

    The past century was era of linear systems. Either systems (especially industrial ones) were simple (quasi)linear or linear approximations were accurate enough. In addition, just at the ending decades of the century profusion of computing devices were available, before then due to lack of computational resources it was not easy to evaluate available nonlinear system studies. At the moment both these two conditions changed, systems are highly complex and also pervasive amount of computation strength is cheap and easy to achieve. For recent era, a new branch of supervised learning well known as surrogate modeling (meta-modeling, surface modeling) has been devised which aimed at answering new needs of modeling realm. This short literature survey is on to introduce surrogate modeling to whom is familiar with the concepts of supervised learning. Necessity, challenges and visions of the topic are considered.

  15. A Parallel and Distributed Surrogate Model Implementation for Computational Steering

    KAUST Repository

    Butnaru, Daniel

    2012-06-01

    Understanding the influence of multiple parameters in a complex simulation setting is a difficult task. In the ideal case, the scientist can freely steer such a simulation and is immediately presented with the results for a certain configuration of the input parameters. Such an exploration process is however not possible if the simulation is computationally too expensive. For these cases we present in this paper a scalable computational steering approach utilizing a fast surrogate model as substitute for the time-consuming simulation. The surrogate model we propose is based on the sparse grid technique, and we identify the main computational tasks associated with its evaluation and its extension. We further show how distributed data management combined with the specific use of accelerators allows us to approximate and deliver simulation results to a high-resolution visualization system in real-time. This significantly enhances the steering workflow and facilitates the interactive exploration of large datasets. © 2012 IEEE.

  16. The Theory and Practice of Surrogate Decision-Making.

    Science.gov (United States)

    Wendler, David

    2017-01-01

    When a patient lacks decision-making capacity and has not left a clear advance directive, there is now widespread agreement that patient-designated and next-of-kin surrogates should implement substituted judgment within a process of shared decision-making. Specifically, after discussing the "best scientific evidence available, as well as the patient's values, goals, and preferences" with the patient's clinicians, the patient-designated or next-of-kin surrogate should attempt to determine what decision the patient would have made in the circumstances. To the extent that this approach works, it seems to provide about as much respect for the autonomy of incapacitated patients as we could ask for. But, as articles in this issue of the Report by Jeffrey Berger and by Ellen Robinson and colleagues emphasize, reality presents challenges. © 2017 The Hastings Center.

  17. Commercial agencies and surrogate motherhood: a transaction cost approach.

    Science.gov (United States)

    Galbraith, Mhairi; McLachlan, Hugh V; Swales, J Kim

    2005-03-01

    In this paper we investigate the legal arrangements involved in UK surrogate motherhood from a transaction-cost perspective. We outline the specific forms the transaction costs take and critically comment on the way in which the UK institutional and organisational arrangements at present adversely influence transaction costs. We then focus specifically on the potential role of surrogacy agencies and look at UK and US evidence on commercial and voluntary agencies. Policy implications follow.

  18. Quantification of the Relationship between Surrogate Fuel Structure and Performance

    Science.gov (United States)

    2012-07-31

    cycloperoxy-5-yl (BICYC5.O2) and bicyclo[2,2,1]hexene peroxy (C2O2H221) radicals . The latter route leads to the formation of vinyl ketene and the formyl ...3089 selection of stable molecule and radicals . The adopted calculation method for the determination of such data is outlined in Appendix 1...chemistry of aromatic fuel components used in surrogate fuels and the importance of the cyclopentadi- enyl radical in poly-aromatic hydrocarbon (PAH

  19. Biopolicies and biotechnologies: reflections on surrogate maternity in India

    OpenAIRE

    Mónica Amador

    2010-01-01

    This article explores the impact of biotechnology, particularly on assisted reproductive technologies such as surrogate motherhood. The study is based on interviews and field work conducted in the city of Hyderabad in India within the frame of the seminar on “Research Methodology” given by Dr. Rohan D´Souza at the Centre for Studies in Science Policy at the Jawaharlal Nehru University in India. The theoretical framework of this analysis focuses on exploring concepts such as cyborg (Haraway,19...

  20. Regression calibration with more surrogates than mismeasured variables

    KAUST Repository

    Kipnis, Victor

    2012-06-29

    In a recent paper (Weller EA, Milton DK, Eisen EA, Spiegelman D. Regression calibration for logistic regression with multiple surrogates for one exposure. Journal of Statistical Planning and Inference 2007; 137: 449-461), the authors discussed fitting logistic regression models when a scalar main explanatory variable is measured with error by several surrogates, that is, a situation with more surrogates than variables measured with error. They compared two methods of adjusting for measurement error using a regression calibration approximate model as if it were exact. One is the standard regression calibration approach consisting of substituting an estimated conditional expectation of the true covariate given observed data in the logistic regression. The other is a novel two-stage approach when the logistic regression is fitted to multiple surrogates, and then a linear combination of estimated slopes is formed as the estimate of interest. Applying estimated asymptotic variances for both methods in a single data set with some sensitivity analysis, the authors asserted superiority of their two-stage approach. We investigate this claim in some detail. A troubling aspect of the proposed two-stage method is that, unlike standard regression calibration and a natural form of maximum likelihood, the resulting estimates are not invariant to reparameterization of nuisance parameters in the model. We show, however, that, under the regression calibration approximation, the two-stage method is asymptotically equivalent to a maximum likelihood formulation, and is therefore in theory superior to standard regression calibration. However, our extensive finite-sample simulations in the practically important parameter space where the regression calibration model provides a good approximation failed to uncover such superiority of the two-stage method. We also discuss extensions to different data structures.

  1. Biopolicies and biotechnologies: reflections on surrogate maternity in India

    OpenAIRE

    Mónica Amador

    2010-01-01

    This article explores the impact of biotechnology, particularly on assisted reproductive technologies such as surrogate motherhood. The study is based on interviews and field work conducted in the city of Hyderabad in India within the frame of the seminar on “Research Methodology” given by Dr. Rohan D´Souza at the Centre for Studies in Science Policy at the Jawaharlal Nehru University in India. The theoretical framework of this analysis focuses on exploring concepts such as cyborg (Haraway,19...

  2. Preparation and in vitro release of ketoprofen sustained-release pellet tablets%酮洛芬微丸缓释片的制备及体外释放度考察

    Institute of Scientific and Technical Information of China (English)

    李海刚; 袁中文; 关世侠; 周郁斌; 胡波; 叶小玲; 杨艳

    2011-01-01

    目的:制备一种酮洛芬缓释片剂.方法:采用挤出-滚圆法制备酮洛芬微丸,用Eudragit(R) RS 30D和Eudragit(R) RL30D包衣.再将包衣微丸与酮洛芬原药压片,最终制成酮洛芬缓释片.结果:体外释放度实验显示,制备的酮洛芬缓释片在2h内能释药30%,剩余70%药物在随后的10h内缓慢释放.结论:用本方法制备酮洛芬缓释片,工艺简便,易于操作.%OBJECTIVE To prepare detoprofen sustained-release tablets. METHODS Extrusion-spheronization technique was introduced to prepare ketoprofen pellets and Eudragir? RS 30D and Eudragit? RL 30D were used as coating materials. Even mix the coated pellets with ketoprofen to prepare ketoprofen sustained-release tablets. RESULTS The data obtained proved that the formulation was useful for a sustained-release of ketoprofen, due to the percentage released in two hours was 30% and in the later ten hours was 70%. CONCLUSION The preparation technology is reliable and easy to operate.

  3. In Situ Formed Phase Transited Drug Delivery System of Ketoprofen for Achieving Osmotic, Controlled and Level A In Vitro In Vivo Correlation

    Science.gov (United States)

    Philip, A. K.; Pathak, Kamla

    2008-01-01

    A dry process induced phase transited, non disintegrating, controlled release, in situ formed asymmetric membrane capsular system for poorly water soluble drug, ketoprofen, was developed and evaluated both in vitro and in vivo for osmotic and controlled release of the drug. In situ formed asymmetric membrane capsules were prepared using fabricated glass capsule holders via dry, phase inversion process. Effect of varying osmotic pressure of the dissolution medium on drug release was studied. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and an inner porous region for the prepared asymmetric membrane. In vitro release studies and statistical test for all the prepared and marketed formulation were done at P >0.05. The drug release was found to be independent of the pH, but dependent on the osmotic pressure of the dissolution medium. In vivo pharmacokinetic studies showed a level A correlation (R2>0.99) with 39.24 % relative bioavailability compared to immediate release tablet of ketoprofen. Excellent correlation achieved suggested that the in vivo performance of the phase transited in situ formed AMCs could be accurately predicted from their in vitro release profiles and could a means for controlled delivery of drugs with varying solubility. PMID:21369435

  4. Supercritical fluid precipitation of ketoprofen in novel structured lipid carriers for enhanced mucosal delivery--a comparison with solid lipid particles.

    Science.gov (United States)

    Gonçalves, V S S; Matias, A A; Rodríguez-Rojo, S; Nogueira, I D; Duarte, C M M

    2015-11-10

    Structured lipid carriers based on mixture of solid lipids with liquid lipids are the second generation of solid lipid particles, offering the advantage of improved drug loading capacity and higher storage stability. In this study, structured lipid carriers were successfully prepared for the first time by precipitation from gas saturated solutions. Glyceryl monooleate (GMO), a liquid glycerolipid, was selected in this work to be incorporated into three solid glycerolipids with hydrophilic-lipophilic balance (HLB) ranging from 1 to 13, namely Gelucire 43/01™, Geleol™ and Gelucire 50/13™. In general, microparticles with a irregular porous morphology and a wide particle size distribution were obtained. The HLB of the individual glycerolipids might be a relevant parameter to take into account during the processing of solid:liquid lipid blends. As expected, the addition of a liquid lipid into a solid lipid matrix led to increased stability of the lipid carriers, with no significant modifications in their melting enthalpy after 6 months of storage. Additionally, Gelucire 43/01™:GMO particles were produced with different mass ratios and loaded with ketoprofen. The drug loading capacity of the structured lipid carriers increased as the GMO content in the particles increased, achieving a maximum encapsulation efficiency of 97% for the 3:1 mass ratio. Moreover, structured lipid carriers presented an immediate release of ketoprofen from its matrix with higher permeation through a mucous-membrane model, while solid lipid particles present a controlled release of the drug with less permeation capacity.

  5. In situ formed phase transited drug delivery system of ketoprofen for achieving osmotic, controlled and level a in vitro in vivo correlation

    Directory of Open Access Journals (Sweden)

    Philip A

    2008-01-01

    Full Text Available A dry process induced phase transited, non disintegrating, controlled release, in situ formed asymmetric membrane capsular system for poorly water soluble drug, ketoprofen, was developed and evaluated both in vitro and in vivo for osmotic and controlled release of the drug. In situ formed asymmetric membrane capsules were prepared using fabricated glass capsule holders via dry, phase inversion process. Effect of varying osmotic pressure of the dissolution medium on drug release was studied. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and an inner porous region for the prepared asymmetric membrane. In vitro release studies and statistical test for all the prepared and marketed formulation were done at P > 0.05. The drug release was found to be independent of the pH, but dependent on the osmotic pressure of the dissolution medium. In vivo pharmacokinetic studies showed a level A correlation (R 2> 0.99 with 39.24 % relative bioavailability compared to immediate release tablet of ketoprofen. Excellent correlation achieved suggested that the in vivo performance of the phase transited in situ formed AMCs could be accurately predicted from their in vitro release profiles and could a means for controlled delivery of drugs with varying solubility.

  6. Liquid chromatographic enantioseparation of three beta-adrenolytics using new derivatizing reagents synthesized from (S)-ketoprofen and confirmation of configuration of diastereomers.

    Science.gov (United States)

    Alwera, Shiv; Bhushan, Ravi

    2016-11-01

    Diastereomers of racemic β-adrenolytic drugs [namely (RS)-propranolol, (RS)-metoprolol and (RS)-atenolol] were synthesized under microwave irradiation with (S)-ketoprofen based chiral derivatization reagents (CDRs) newly synthesized for this purpose. (S)-Ketoprofen was chosen for its high molar absorptivity (εo  ~ 40,000) and its availability as a pure (S)-enantiomer. Its -COOH group was activated with N-hydroxysuccinimide and N-hydroxybenzotriazole; these were easily introduced and also acted as good leaving groups during nucleophilic substitution by the amino group of the racemic β-adrenolytics. The CDRs were characterized by UV, IR, (1) H-NMR, HRMS and CHNS. Separation of diastereomers was achieved by RP HPLC and open column chromatography. Absolute configuration of the diastereomers was established with the help of (1) HNMR supported by developing their optimized lowest energy structures using Gaussian 09 Rev. A.02 program and hybrid density functional B3LYP with 6-31G* basis set (based on density functional theory), and elution order was established. RP HPLC conditions for separation were optimized and the separation method was validated. The limit of detection values were 0.308 and 0.302 ng mL(-1) . Copyright © 2016 John Wiley & Sons, Ltd.

  7. Novel binuclear μ-oxo diruthenium complexes combined with ibuprofen and ketoprofen: Interaction with relevant target biomolecules and anti-allergic potential.

    Science.gov (United States)

    Seuanes, Gabriela Campos; Moreira, Mariete Barbosa; Petta, Tânia; de Moraes Del Lama, Maria Perpétua Freire; de Moraes, Luiz Alberto Beraldo; de Oliveira, Anderson Rodrigo Moraes; Naal, Rose Mary Zumstein Georgetto; Nikolaou, Sofia

    2015-12-01

    This work presents the synthesis and characterization of two novel binuclear ruthenium compounds of general formula [Ru2O(carb)2(py)6](PF6)2, where py=pyridine and carb are the non-steroidal anti-inflammatory drugs ibuprofen (1) and ketoprofen (2). Both complexes were characterized by ESI-MS/MS spectrometry. The fragmentation patterns, which confirm the proposed structures, are presented. Besides that, compounds 1 and 2 present the charge transfer transitions within 325-330nm; and the intra-core transitions around 585nm, which is the typical spectra profile for [Ru2O] analogues. This suggests the carboxylate bridge has little influence in their electronic structure. The effects of the diruthenium complexes on Ig-E mediated mast cell activation were evaluated by measuring the enzyme β-hexosaminidase released by mast cells stimulated by antigen. The inhibitory potential of the ketoprofen complex against mast cell stimulation suggests its promising application as a therapeutic agent for treating or preventing IgE-mediated allergic diseases. In addition, in vitro metabolism assays had shown that the ibuprofen complex is metabolized by the cytochrome P450 enzymes.

  8. Diaphragm as an anatomic surrogate for lung tumor motion

    CERN Document Server

    Cervino, Laura I; Sandhu, Ajay; Jiang, Steve B

    2009-01-01

    Lung tumor motion due to respiration poses a challenge in the application of modern three-dimensional conformal radiotherapy. Direct tracking of the lung tumor during radiation therapy is very difficult without implanted fiducial markers. Indirect tracking relies on the correlation of the tumor's motion and the surrogate's motion. The present paper presents an analysis of the correlation between the tumor motion and the diaphragm motion in order to evaluate the potential use of diaphragm as a surrogate for tumor motion. We have analyzed the correlation between diaphragm motion and superior-inferior lung tumor motion in 32 fluoroscopic image sequences from 10 lung cancer patients. A simple linear model and a more complex linear model that accounts for phase delays between the two motions have been used. Results show that the diaphragm is a good surrogate for tumor motion prediction for most patients, resulting in an average correlation factor of 0.94 and 0.98 with each model respectively. The model that accoun...

  9. The Confucian bioethics of surrogate decision making: its communitarian roots.

    Science.gov (United States)

    Fan, Ruiping

    2011-10-01

    The family is the exemplar community of Chinese society. This essay explores how Chinese communitarian norms, expressed in thick commitments to the authority and autonomy of the family, are central to contemporary Chinese bioethics. In particular, it focuses on the issue of surrogate decision making to illustrate the Confucian family-grounded communitarian bioethics. The essay first describes the way in which the family, in Chinese bioethics, functions as a whole to provide consent for significant medical and surgical interventions when a patient has lost decision-making capacity. It is argued that the practice of not having an established order for surrogate decision makers (e.g., spouse, children, and then parents), as it is done in the United States, reflects the acknowledgment that the family as a social reality cannot be reduced to a stereotype of the appropriate order of default decision makers. This description of the family as being in authority to make surrogate decisions for an incompetent family member is enriched by an elaboration of the differences among the concepts of patient autonomy, family autonomy, and moral autonomy. The Chinese model, as well as the Confucian communitarian life of families, engages a family autonomy that is supported by a Confucian understanding of moral autonomy, rather than individual autonomy. Finally, the issue of possible conflicts between patient and family interests in relation to a patient's past wishes in the Chinese model is addressed in light of the role of the physician.

  10. Evaluation of bone surrogates for indirect and direct ballistic fractures.

    Science.gov (United States)

    Bir, Cynthia; Andrecovich, Chris; DeMaio, Marlene; Dougherty, Paul J

    2016-04-01

    The mechanism of injury for fractures to long bones has been studied for both direct ballistic loading as well as indirect. However, the majority of these studies have been conducted on both post-mortem human subjects (PMHS) and animal surrogates which have constraints in terms of storage, preparation and testing. The identification of a validated bone surrogate for use in forensic, medical and engineering testing would provide the ability to investigate ballistic loading without these constraints. Two specific bone surrogates, Sawbones and Synbone, were evaluated in comparison to PMHS for both direct and indirect ballistic loading. For the direct loading, the mean velocity to produce fracture was 121 ± 19 m/s for the PMHS, which was statistically different from the Sawbones (140 ± 7 m/s) and Synbone (146 ± 3 m/s). The average distance to fracture in the indirect loading was .70 cm for the PMHS. The Synbone had a statistically similar average distance to fracture (.61 cm, p=0.54) however the Sawbones average distance to fracture was statistically different (.41 cm, pballistic testing was not identified and future work is warranted.

  11. Surrogate Assisted Design Optimization of an Air Turbine

    Directory of Open Access Journals (Sweden)

    Rameez Badhurshah

    2014-01-01

    Full Text Available Surrogates are cheaper to evaluate and assist in designing systems with lesser time. On the other hand, the surrogates are problem dependent and they need evaluation for each problem to find a suitable surrogate. The Kriging variants such as ordinary, universal, and blind along with commonly used response surface approximation (RSA model were used in the present problem, to optimize the performance of an air impulse turbine used for ocean wave energy harvesting by CFD analysis. A three-level full factorial design was employed to find sample points in the design space for two design variables. A Reynolds-averaged Navier Stokes solver was used to evaluate the objective function responses, and these responses along with the design variables were used to construct the Kriging variants and RSA functions. A hybrid genetic algorithm was used to find the optimal point in the design space. It was found that the best optimal design was produced by the universal Kriging while the blind Kriging produced the worst. The present approach is suggested for renewable energy application.

  12. Effectiveness of biological surrogates for predicting patterns of marine biodiversity: a global meta-analysis.

    Directory of Open Access Journals (Sweden)

    Camille Mellin

    Full Text Available The use of biological surrogates as proxies for biodiversity patterns is gaining popularity, particularly in marine systems where field surveys can be expensive and species richness high. Yet, uncertainty regarding their applicability remains because of inconsistency of definitions, a lack of standard methods for estimating effectiveness, and variable spatial scales considered. We present a Bayesian meta-analysis of the effectiveness of biological surrogates in marine ecosystems. Surrogate effectiveness was defined both as the proportion of surrogacy tests where predictions based on surrogates were better than random (i.e., low probability of making a Type I error; P and as the predictability of targets using surrogates (R(2. A total of 264 published surrogacy tests combined with prior probabilities elicited from eight international experts demonstrated that the habitat, spatial scale, type of surrogate and statistical method used all influenced surrogate effectiveness, at least according to either P or R(2. The type of surrogate used (higher-taxa, cross-taxa or subset taxa was the best predictor of P, with the higher-taxa surrogates outperforming all others. The marine habitat was the best predictor of R(2, with particularly low predictability in tropical reefs. Surrogate effectiveness was greatest for higher-taxa surrogates at a <10-km spatial scale, in low-complexity marine habitats such as soft bottoms, and using multivariate-based methods. Comparisons with terrestrial studies in terms of the methods used to study surrogates revealed that marine applications still ignore some problems with several widely used statistical approaches to surrogacy. Our study provides a benchmark for the reliable use of biological surrogates in marine ecosystems, and highlights directions for future development of biological surrogates in predicting biodiversity.

  13. SU-E-J-73: Generation of Volumetric Images with a Respiratory Motion Model Based On An External Surrogate Signal

    Energy Technology Data Exchange (ETDEWEB)

    Hurwitz, M; Williams, C; Mishra, P; Dhou, S; Lewis, J [Brigham and Women' s Hospital, Dana-Farber Cancer Center, Harvard Medical School, Boston, MA, Boston, MA (United States)

    2014-06-01

    Purpose: Respiratory motion during radiotherapy treatment can differ significantly from motion observed during imaging for treatment planning. Our goal is to use an initial 4DCT scan and the trace of an external surrogate marker to generate 3D images of patient anatomy during treatment. Methods: Deformable image registration is performed on images from an initial 4DCT scan. The deformation vectors are used to develop a patient-specific linear relationship between the motion of each voxel and the trajectory of an external surrogate signal. Correlations in motion are taken into account with principal component analysis, reducing the number of free parameters. This model is tested with digital phantoms reproducing the breathing patterns of ten measured patient tumor trajectories, using five seconds of data to develop the model and the subsequent thirty seconds to test its predictions. The model is also tested with a breathing physical anthropomorphic phantom programmed to reproduce a patient breathing pattern. Results: The error (mean absolute, 95th percentile) over 30 seconds in the predicted tumor centroid position ranged from (0.8, 1.3) mm to (2.2, 4.3) mm for the ten patient breathing patterns. The model reproduced changes in both phase and amplitude of the breathing pattern. Agreement between prediction and truth over the entire image was confirmed by assessing the global voxel intensity RMS error. In the physical phantom, the error in the tumor centroid position was less than 1 mm for all images. Conclusion: We are able to reconstruct 3D images of patient anatomy with a model correlating internal respiratory motion with motion of an external surrogate marker, reproducing the expected tumor centroid position with an average accuracy of 1.4 mm. The images generated by this model could be used to improve dose calculations for treatment planning and delivered dose estimates. This work was partially funded by a research grant from Varian Medical Systems.

  14. Surrogate model based iterative ensemble smoother for subsurface flow data assimilation

    Science.gov (United States)

    Chang, Haibin; Liao, Qinzhuo; Zhang, Dongxiao

    2017-02-01

    Subsurface geological formation properties often involve some degree of uncertainty. Thus, for most conditions, uncertainty quantification and data assimilation are necessary for predicting subsurface flow. The surrogate model based method is one common type of uncertainty quantification method, in which a surrogate model is constructed for approximating the relationship between model output and model input. Based on the prediction ability, the constructed surrogate model can be utilized for performing data assimilation. In this work, we develop an algorithm for implementing an iterative ensemble smoother (ES) using the surrogate model. We first derive an iterative ES scheme using a regular routine. In order to utilize surrogate models, we then borrow the idea of Chen and Oliver (2013) to modify the Hessian, and further develop an independent parameter based iterative ES formula. Finally, we establish the algorithm for the implementation of iterative ES using surrogate models. Two surrogate models, the PCE surrogate and the interpolation surrogate, are introduced for illustration. The performances of the proposed algorithm are tested by synthetic cases. The results show that satisfactory data assimilation results can be obtained by using surrogate models that have sufficient accuracy.

  15. Immunomodulatory properties of gamithromycin and ketoprofen in lipopolysaccharide-challenged calves with emphasis on the acute-phase response.

    Science.gov (United States)

    Plessers, Elke; Wyns, Heidi; Watteyn, Anneleen; Pardon, Bart; De Baere, Siegrid; Sys, Stanislas U; De Backer, Patrick; Croubels, Siska

    2016-03-01

    Macrolide antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to be modulators of the innate immune response, irrespectively of their antimicrobial and anti-inflammatory actions. Therefore, it was our objective to evaluate whether the macrolide gamithromycin (GAM) and the NSAID ketoprofen (KETO) attenuate the acute-phase response in calves, and whether their combined administration is beneficial due to synergistic and/or additive effects. To this end, both drugs, as well as their combination, were studied in a previously developed inflammation model, i.e., the induction of an acute-phase response by an intravenous lipopolysaccharide (LPS) challenge (0.5 μg/kg body weight). Sixteen 4-week-old Holstein-Friesian calves were randomized into 4 groups: a positive control (+CONTR) group, receiving LPS but no pharmacological treatment (n=4) and a GAM (n=4), a KETO (n=4) and a GAM-KETO (n=4) group, receiving the respective drugs 1h prior to LPS administration. Clinical scoring and blood collection were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of the selected cytokines (tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6)), acute-phase protein (serum amyloid A (SAA)) and prostaglandin E2 (PGE2) were subsequently quantified. Pre-treatment with GAM had no effect in the inflammation model compared to the +CONTR group. KETO, on the other hand, completely inhibited depression, anorexia and fever. This remarkable influence was associated with a significant reduction of PGE2 synthesis by KETO, while the effect on TNF-α, IL-6 and SAA was not straightforward. The combined administration of GAM and KETO provided no synergistic or additive effects in this model, neither clinically nor regarding the studied inflammatory mediators. In conclusion, KETO entirely inhibited PGE2 synthesis, fever development and depression, while GAM did not exert any effect in this model. These results promote the concomitant

  16. The 13C-Glucose Breath Test for Insulin Resistance Assessment in Adolescents: Comparison with Fasting and Post-Glucose Stimulus Surrogate Markers of Insulin Resistance

    OpenAIRE

    Maldonado-Hernández, Jorge; Martínez-Basila, Azucena; Salas-Fernández, Alejandra; Navarro-Betancourt, José R.; Piña-Aguero, Mónica I.; Bernabe-García, Mariela

    2016-01-01

    Objective: To evaluate the use of the 13C-glucose breath test (13C-GBT) for insulin resistance (IR) detection in adolescents through comparison with fasting and post-glucose stimulus surrogates. Methods: One hundred thirty-three adolescents aged between 10 and 16 years received an oral glucose load of 1.75 g per kg of body weight dissolved in 150 mL of water followed by an oral dose of 1.5 mg/kg of U-13C-Glucose, without a specific maximum dose. Blood samples were drawn at baseline and 120 mi...

  17. Uncertainty quantification of squeal instability via surrogate modelling

    Science.gov (United States)

    Nobari, Amir; Ouyang, Huajiang; Bannister, Paul

    2015-08-01

    One of the major issues that car manufacturers are facing is the noise and vibration of brake systems. Of the different sorts of noise and vibration, which a brake system may generate, squeal as an irritating high-frequency noise costs the manufacturers significantly. Despite considerable research that has been conducted on brake squeal, the root cause of squeal is still not fully understood. The most common assumption, however, is mode-coupling. Complex eigenvalue analysis is the most widely used approach to the analysis of brake squeal problems. One of the major drawbacks of this technique, nevertheless, is that the effects of variability and uncertainty are not included in the results. Apparently, uncertainty and variability are two inseparable parts of any brake system. Uncertainty is mainly caused by friction, contact, wear and thermal effects while variability mostly stems from the manufacturing process, material properties and component geometries. Evaluating the effects of uncertainty and variability in the complex eigenvalue analysis improves the predictability of noise propensity and helps produce a more robust design. The biggest hurdle in the uncertainty analysis of brake systems is the computational cost and time. Most uncertainty analysis techniques rely on the results of many deterministic analyses. A full finite element model of a brake system typically consists of millions of degrees-of-freedom and many load cases. Running time of such models is so long that automotive industry is reluctant to do many deterministic analyses. This paper, instead, proposes an efficient method of uncertainty propagation via surrogate modelling. A surrogate model of a brake system is constructed in order to reproduce the outputs of the large-scale finite element model and overcome the issue of computational workloads. The probability distribution of the real part of an unstable mode can then be obtained by using the surrogate model with a massive saving of

  18. Compaction behavior of surrogate degraded emplaced WIPP waste.

    Energy Technology Data Exchange (ETDEWEB)

    Broome, Scott Thomas [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bronowski, David R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kuthakun, Souvanny James [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Herrick, Courtney Grant [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Pfeifle, Thomas W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-03-01

    The present study results are focused on laboratory testing of surrogate waste materials. The surrogate wastes correspond to a conservative estimate of degraded Waste Isolation Pilot Plant (WIPP) containers and TRU waste materials at the end of the 10,000 year regulatory period. Testing consists of hydrostatic, triaxial, and uniaxial strain tests performed on surrogate waste recipes that were previously developed by Hansen et al. (1997). These recipes can be divided into materials that simulate 50% and 100% degraded waste by weight. The percent degradation indicates the anticipated amount of iron corrosion, as well as the decomposition of cellulosics, plastics, and rubbers (CPR). Axial, lateral, and volumetric strain and axial, lateral, and pore stress measurements were made. Two unique testing techniques were developed during the course of the experimental program. The first involves the use of dilatometry to measure sample volumetric strain under a hydrostatic condition. Bulk moduli of the samples measured using this technique were consistent with those measured using more conventional methods. The second technique involved performing triaxial tests under lateral strain control. By limiting the lateral strain to zero by controlling the applied confining pressure while loading the specimen axially in compression, one can maintain a right-circular cylindrical geometry even under large deformations. This technique is preferred over standard triaxial testing methods which result in inhomogeneous deformation or (3z(Bbarreling(3y. (BManifestations of the inhomogeneous deformation included non-uniform stress states, as well as unrealistic Poissons ratios (> 0.5) or those that vary significantly along the length of the specimen. Zero lateral strain controlled tests yield a more uniform stress state, and admissible and uniform values of Poissons ratio.

  19. [Comparative enantioselectivity of the disposition of two non-steroidal anti-inflammatory agents, ketoprofen and carprofen, in man and animals].

    Science.gov (United States)

    Delatour, P; Benoit, E; Bourdin, M; Gobron, M; Moysan, F

    1993-03-01

    After the administration of racemic ketoprofen and carprofen to man, both enantiomers of each compound exhibit similar plasma profiles. This contrasts with the rat where the active S(+) enantiomer is predominant. For carprofen, regardless of the route of administration, the R(-) enantiomer is predominant in the plasma of all investigated animal species. The S(+)/R(-) ratio of the "areas under the curves" during the time course of the kinetics, is: 0.60 in dogs, 0.53 in Yucatan micro-pigs, 0.48 in mini-goats, 0.67 in calves and 0.19 in horses. For ketoprofen, the S(+) enantiomer is predominant in dogs, cats and horses, with ratios of 30.3, 5.3 and 1.5, respectively, while R(-) is the predominant enantiomer in sheep. The interpretation of these inter-species differences can be supported by experimental evidence, however some informations are lacking and additional investigation is required. In the case of ketoprofen where S(+) is predominant in rats, dogs and horses, the metabolic chiral inversion from R(-) to S(+), which has been demonstrated in rats, may also take place in the latter two species. In addition, the well documented stereoselective clearance of the glucuronides, possibly in favour of the enantiomer S(+), may explain the lower body clearance of the R(-) enantiomer in sheep. For carprofen, no metabolic chiral inversion was shown in rats and dogs after administration of each enantiomer individually, but for this compound, stereoselective clearance of glucuronides has been demonstrated which may support the idea of a plasma concentration shift of the enantiomeric proportions vs time in favour of the R(-) enantiomer. Regardless of the possible biological mechanisms which are responsible for these inter-species differences, the existence of these differences gives rise to at least two important issues: The choice of animal species which can be used in the research of drugs destined for human therapeutics: the most pertinent animal species will be the one

  20. Biopolicies and biotechnologies: reflections on surrogate maternity in India

    Directory of Open Access Journals (Sweden)

    Mónica Amador

    2010-07-01

    Full Text Available This article explores the impact of biotechnology, particularly on assisted reproductive technologies such as surrogate motherhood. The study is based on interviews and field work conducted in the city of Hyderabad in India within the frame of the seminar on “Research Methodology” given by Dr. Rohan D´Souza at the Centre for Studies in Science Policy at the Jawaharlal Nehru University in India. The theoretical framework of this analysis focuses on exploring concepts such as cyborg (Haraway,1991 and subaltern subject (Spivak, 1998 in the context of biotechnological production in India

  1. Surrogate based approaches to parameter inference in ocean models

    KAUST Repository

    Knio, Omar

    2016-01-06

    This talk discusses the inference of physical parameters using model surrogates. Attention is focused on the use of sampling schemes to build suitable representations of the dependence of the model response on uncertain input data. Non-intrusive spectral projections and regularized regressions are used for this purpose. A Bayesian inference formalism is then applied to update the uncertain inputs based on available measurements or observations. To perform the update, we consider two alternative approaches, based on the application of Markov Chain Monte Carlo methods or of adjoint-based optimization techniques. We outline the implementation of these techniques to infer dependence of wind drag, bottom drag, and internal mixing coefficients.

  2. 酮洛芬磺丁基醚-β-环糊精包合物的制备%Preparation of inclusion compound with ketoprofen and sulfobutyl ether-β-cyclodextrin

    Institute of Scientific and Technical Information of China (English)

    归银兰; 归小龙

    2012-01-01

    目的:制备酮洛芬磺丁基醚-β-环糊精包合物,以增加酮洛芬的溶出度和生物利用度.方法:通过研究酮洛芬与磺丁基醚-β-环糊精的平衡相溶解度,筛选主客分子的比例以及制备方法,以冷冻干燥法制备酮洛芬磺丁基醚-β-环糊精包合物.差示扫描热分析验证包合物的生成,测定包合物的包合率和含量,测定包合物中酮洛芬的溶出度和大鼠体内血药浓度并与原料酮洛芬做比较.结果:磺丁基醚-β-环糊精与酮洛芬的表观稳定常数为686.38 L·mol-1,两者是以摩尔比1∶1包合.包合物的包合率为(95.14±1.41)%,在0.1 mol·L-1盐酸中30 min的溶出度以达到90%,而酮洛芬只有35%,包合物在大鼠体内AUC0-∞为(28.6±8.54) μg·mL-1,而酮洛芬为(10.06±4.54)μg·mL-1.结论:使用磺丁基醚-β-环糊精制备包合物能增加酮洛芬的溶出度及提高生物利用度.%OBJECTIVE To prepare the inclusion compound with ketoprofen and sulfobutyl ether-β-cyclodextrin for improving the dissolution rate and bioavailability of ketoprofen. METHODS The ratio of ketoprofen and salfobutyl ether-β-cyclodextrin and preparation methods were screened by phase solubility studies. The inclusion compounds were prepared by lyophiliza-tion. The forming of inclusion compounds was validated by differential scanning calorimetry. The inclusion ratio and content of inclusion compounds were determined. In vitro dissolution rate and in vivo plasma drug concentration in rats were compared with those of bulk ketoprofen. RESULTS The stability constant (Kc) of phase solubility curve was 686. 38 L·mol-1. The ketoprofen was included in sulfobutyl ether-β-cyclodextrin with 1 : 1 molar ratio. The inclusion ratio of inclusion compounds were (95. 14 ± 1. 41)%. The ketoprofen in inclusion compound and bulk ketoprofen released after 30 min in 0. 1 mol·L-1 HCl were approximately 90% and 35%. AUCn0-∞, of inclusion compound and bulk ketoprofen were (28. 6

  3. Diesel Surrogate Fuels for Engine Testing and Chemical-Kinetic Modeling: Compositions and Properties

    Science.gov (United States)

    Mueller, Charles J.; Cannella, William J.; Bays, J. Timothy; Bruno, Thomas J.; DeFabio, Kathy; Dettman, Heather D.; Gieleciak, Rafal M.; Huber, Marcia L.; Kweon, Chol-Bum; McConnell, Steven S.; Pitz, William J.; Ratcliff, Matthew A.

    2016-01-01

    The primary objectives of this work were to formulate, blend, and characterize a set of four ultralow-sulfur diesel surrogate fuels in quantities sufficient to enable their study in single-cylinder-engine and combustion-vessel experiments. The surrogate fuels feature increasing levels of compositional accuracy (i.e., increasing exactness in matching hydrocarbon structural characteristics) relative to the single target diesel fuel upon which the surrogate fuels are based. This approach was taken to assist in determining the minimum level of surrogate-fuel compositional accuracy that is required to adequately emulate the performance characteristics of the target fuel under different combustion modes. For each of the four surrogate fuels, an approximately 30 L batch was blended, and a number of the physical and chemical properties were measured. This work documents the surrogate-fuel creation process and the results of the property measurements. PMID:27330248

  4. Fast and accurate prediction of numerical relativity waveforms from binary black hole mergers using surrogate models

    CERN Document Server

    Blackman, Jonathan; Galley, Chad R; Szilagyi, Bela; Scheel, Mark A; Tiglio, Manuel; Hemberger, Daniel A

    2015-01-01

    Simulating a binary black hole coalescence by solving Einstein's equations is computationally expensive, requiring days to months of supercomputing time. In this paper, we construct an accurate and fast-to-evaluate surrogate model for numerical relativity (NR) waveforms from non-spinning binary black hole coalescences with mass ratios from $1$ to $10$ and durations corresponding to about $15$ orbits before merger. Our surrogate, which is built using reduced order modeling techniques, is distinct from traditional modeling efforts. We find that the full multi-mode surrogate model agrees with waveforms generated by NR to within the numerical error of the NR code. In particular, we show that our modeling strategy produces surrogates which can correctly predict NR waveforms that were {\\em not} used for the surrogate's training. For all practical purposes, then, the surrogate waveform model is equivalent to the high-accuracy, large-scale simulation waveform but can be evaluated in a millisecond to a second dependin...

  5. Combining endangered plants and animals as surrogates to identify priority conservation areas in Yunnan, China

    OpenAIRE

    Feiling Yang; Jinming Hu; Ruidong Wu

    2016-01-01

    Suitable surrogates are critical for identifying optimal priority conservation areas (PCAs) to protect regional biodiversity. This study explored the efficiency of using endangered plants and animals as surrogates for identifying PCAs at the county level in Yunnan, southwest China. We ran the Dobson algorithm under three surrogate scenarios at 75% and 100% conservation levels and identified four types of PCAs. Assessment of the protection efficiencies of the four types of PCAs showed that end...

  6. Surrogate Mobility and Orientation Affect the Early Neurobehavioral Development of Infant Rhesus Macaques (Macaca mulatta)

    OpenAIRE

    Amanda M Dettmer; Ruggerio, Angela M.; Novak, Melinda A.; Meyer, Jerrold S.; Suomi, Stephen J.

    2008-01-01

    A biological mother’s movement appears necessary for optimal development in infant monkeys. However, nursery-reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard...

  7. Evaluation of the use of surrogate Laminaria digitata in eco-hydraulic laboratory experiments

    Institute of Scientific and Technical Information of China (English)

    PAUL Maike; HENRY Pierre-Yves T

    2014-01-01

    Inert surrogates can avoid husbandry and adaptation problems of live vegetation in laboratories. Surrogates are generally used for experiments on vegetation-hydrodynamics interactions, but it is unclear how well they replicate field conditions. Here, surrogates for the brown macroalgae Laminaria digitata were developed to reproduce its hydraulic roughness. Plant shape, stiffness and buoyancy of L. digitata were evaluated and compared to the properties of inert materials. Different surrogate materials and shapes were exposed to unidirectional flow. It is concluded that buoyancy is an important factor in low flow conditions and a basic shape might be sufficient to model complex shaped plants resulting in the same streamlined shape.

  8. The use of surrogate endpoints in regulating medicines for cardio-renal disease: opinions of stakeholders.

    Directory of Open Access Journals (Sweden)

    Bauke Schievink

    Full Text Available AIM: There is discussion whether medicines can be authorized on the market based on evidence from surrogate endpoints. We assessed opinions of different stakeholders on this topic. METHODS: We conducted an online questionnaire that targeted various stakeholder groups (regulatory agencies, pharmaceutical industry, academia, relevant public sector organisations and medical specialties (cardiology or nephrology vs. other. Participants were enrolled through purposeful sampling. We inquired for conditions under which surrogate endpoints can be used, the validity of various cardio-renal biomarkers and new approaches for biomarker use. RESULTS: Participants agreed that surrogate endpoints can be used when the surrogate is scientifically valid (5-point Likert response format, mean score: 4.3, SD: 0.9 or when there is an unmet clinical need (mean score: 3.8, SD: 1.2. Industry participants agreed to a greater extent than regulators and academics. However, out of four proposed surrogates (blood pressure (BP, HbA1c, albuminuria, CRP for cardiovascular outcomes or end-stage renal disease, only use of BP for cardiovascular outcomes was deemed moderately accurate (mean: 3.6, SD: 1.1. Specialists in cardiology or nephrology tended to be more positive about the use of surrogate endpoints. CONCLUSION: Stakeholders in drug development do not oppose to the use of surrogate endpoints in drug marketing authorization, but most surrogates are not considered valid. To solve this impasse, increased efforts are required to validate surrogate endpoints and to explore alternative ways to use them.

  9. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Herbinet, O; Pitz, W J; Westbrook, C K

    2007-09-20

    A detailed chemical kinetic mechanism has been developed and used to study the oxidation of methyl decanoate, a surrogate for biodiesel fuels. This model has been built by following the rules established by Curran et al. for the oxidation of n-heptane and it includes all the reactions known to be pertinent to both low and high temperatures. Computed results have been compared with methyl decanoate experiments in an engine and oxidation of rapeseed oil methyl esters in a jet stirred reactor. An important feature of this mechanism is its ability to reproduce the early formation of carbon dioxide that is unique to biofuels and due to the presence of the ester group in the reactant. The model also predicts ignition delay times and OH profiles very close to observed values in shock tube experiments fueled by n-decane. These model capabilities indicate that large n-alkanes can be good surrogates for large methyl esters and biodiesel fuels to predict overall reactivity, but some kinetic details, including early CO{sub 2} production from biodiesel fuels, can be predicted only by a detailed kinetic mechanism for a true methyl ester fuel. The present methyl decanoate mechanism provides a realistic kinetic tool for simulation of biodiesel fuels.

  10. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Herbinet, O; Pitz, W J; Westbrook, C K

    2007-09-17

    A detailed chemical kinetic mechanism has been developed and used to study the oxidation of methyl decanoate, a surrogate for biodiesel fuels. This model has been built by following the rules established by Curran et al. for the oxidation of n-heptane and it includes all the reactions known to be pertinent to both low and high temperatures. Computed results have been compared with methyl decanoate experiments in an engine and oxidation of rapeseed oil methyl esters in a jet stirred reactor. An important feature of this mechanism is its ability to reproduce the early formation of carbon dioxide that is unique to biofuels and due to the presence of the ester group in the reactant. The model also predicts ignition delay times and OH profiles very close to observed values in shock tube experiments fueled by n-decane. These model capabilities indicate that large n-alkanes can be good surrogates for large methyl esters and biodiesel fuels to predict overall reactivity, but some kinetic details, including early CO2 production from biodiesel fuels, can be predicted only by a detailed kinetic mechanism for a true methyl ester fuel. The present methyl decanoate mechanism provides a realistic kinetic tool for simulation of biodiesel fuels.

  11. Simultaneous Thermal Analysis of Remediated Nitrate Salt Surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Wayne, David Matthew [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-13

    The actinide engineering and science group (MET-1) have completed simultaneous thermal analysis and offgas analysis by mass spectrometry (STA-MS) of remediated nitrate salt (RNS) surrogates formulated by the high explosives science and technology group (M-7). The 1.0 to 1.5g surrogate samples were first analyzed as received, then a new set was analyzed with 100-200mL 10M HNO3 +0.3 MHF added, and a third set was analyzed after 200 mL of a concentrated Pu-AM spike (in 10M HNO3 +0.3 MHF) was added. The acid and spike solutions were formulated by the actinide analytical chemistry group (C-AAC) using reagent-grade HNO3 and HF, which was also used to dissolve a small quantity of mixed, high-fired PuO2/ AmO2 oxide.

  12. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Herbinet, O; Pitz, W J; Westbrook, C K

    2007-09-20

    A detailed chemical kinetic mechanism has been developed and used to study the oxidation of methyl decanoate, a surrogate for biodiesel fuels. This model has been built by following the rules established by Curran et al. for the oxidation of n-heptane and it includes all the reactions known to be pertinent to both low and high temperatures. Computed results have been compared with methyl decanoate experiments in an engine and oxidation of rapeseed oil methyl esters in a jet stirred reactor. An important feature of this mechanism is its ability to reproduce the early formation of carbon dioxide that is unique to biofuels and due to the presence of the ester group in the reactant. The model also predicts ignition delay times and OH profiles very close to observed values in shock tube experiments fueled by n-decane. These model capabilities indicate that large n-alkanes can be good surrogates for large methyl esters and biodiesel fuels to predict overall reactivity, but some kinetic details, including early CO{sub 2} production from biodiesel fuels, can be predicted only by a detailed kinetic mechanism for a true methyl ester fuel. The present methyl decanoate mechanism provides a realistic kinetic tool for simulation of biodiesel fuels.

  13. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Herbinet, O; Pitz, W J; Westbrook, C K

    2007-09-17

    A detailed chemical kinetic mechanism has been developed and used to study the oxidation of methyl decanoate, a surrogate for biodiesel fuels. This model has been built by following the rules established by Curran et al. for the oxidation of n-heptane and it includes all the reactions known to be pertinent to both low and high temperatures. Computed results have been compared with methyl decanoate experiments in an engine and oxidation of rapeseed oil methyl esters in a jet stirred reactor. An important feature of this mechanism is its ability to reproduce the early formation of carbon dioxide that is unique to biofuels and due to the presence of the ester group in the reactant. The model also predicts ignition delay times and OH profiles very close to observed values in shock tube experiments fueled by n-decane. These model capabilities indicate that large n-alkanes can be good surrogates for large methyl esters and biodiesel fuels to predict overall reactivity, but some kinetic details, including early CO2 production from biodiesel fuels, can be predicted only by a detailed kinetic mechanism for a true methyl ester fuel. The present methyl decanoate mechanism provides a realistic kinetic tool for simulation of biodiesel fuels.

  14. Premixed flame chemistry of a gasoline primary reference fuel surrogate

    KAUST Repository

    Selim, Hatem

    2017-03-10

    Investigating the combustion chemistry of gasoline surrogate fuels promises to improve detailed reaction mechanisms used for simulating their combustion. In this work, the combustion chemistry of one of the simplest, but most frequently used gasoline surrogates – primary reference fuel 84 (PRF 84, 84 vol% iso-octane and 16 vol% n-heptane), has been examined in a stoichiometric premixed laminar flame. Time-of-flight mass spectrometry coupled with a vacuum ultraviolet (VUV) synchrotron light source for species photoionization was used. Reactants, major end-products, stable intermediates, free radicals, and isomeric species were detected and quantified. Numerical simulations were conducted using a detailed chemical kinetic model with the most recently available high temperature sub-mechanisms for iso-octane and heptane, built on the top of an updated pentane isomers model and AramcoMech 2.0 (C0C4) base chemistry. A detailed interpretation of the major differences between the mechanistic pathways of both fuel components is given. A comparison between the experimental and numerical results is depicted and rate of production and sensitivity analyses are shown for the species with considerable disagreement between the experimental and numerical findings.

  15. Bayesian Calibration of the Community Land Model using Surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Ray, Jaideep; Hou, Zhangshuan; Huang, Maoyi; Sargsyan, K.; Swiler, Laura P.

    2015-01-01

    We present results from the Bayesian calibration of hydrological parameters of the Community Land Model (CLM), which is often used in climate simulations and Earth system models. A statistical inverse problem is formulated for three hydrological parameters, conditioned on observations of latent heat surface fluxes over 48 months. Our calibration method uses polynomial and Gaussian process surrogates of the CLM, and solves the parameter estimation problem using a Markov chain Monte Carlo sampler. Posterior probability densities for the parameters are developed for two sites with different soil and vegetation covers. Our method also allows us to examine the structural error in CLM under two error models. We find that accurate surrogate models can be created for CLM in most cases. The posterior distributions lead to better prediction than the default parameter values in CLM. Climatologically averaging the observations does not modify the parameters’ distributions significantly. The structural error model reveals a correlation time-scale which can potentially be used to identify physical processes that could be contributing to it. While the calibrated CLM has a higher predictive skill, the calibration is under-dispersive.

  16. Fractional flow reserve as a surrogate for inducible myocardial ischaemia.

    Science.gov (United States)

    van de Hoef, Tim P; Meuwissen, Martijn; Escaned, Javier; Davies, Justin E; Siebes, Maria; Spaan, Jos A E; Piek, Jan J

    2013-08-01

    Documentation of inducible myocardial ischaemia, related to the coronary stenosis of interest, is of increasing importance in lesion selection for percutaneous coronary intervention (PCI). Fractional flow reserve (FFR) is an easily understood, routine diagnostic modality that has become part of daily clinical practice, and is used as a surrogate technique for noninvasive assessment of myocardial ischaemia. However, the application of a single, discrete, cut-off value for FFR-guided lesion selection for PCI, and its adoption in contemporary revascularization guidelines, has limited the requirement for a thorough understanding of the physiological basis of FFR. This limitation constitutes an obstacle for the adequate use and interpretation of this technique, and also for the understanding of new and future modalities of physiological functional intracoronary testing. In this Review, we revisit the fundamental elements of coronary physiology in the absence or presence of coronary artery disease. We provide insight into three essential characteristics of FFR as a diagnostic tool in contemporary clinical practice--the theoretical framework of FFR and its associated limitations; the characteristics and role of FFR as a surrogate for noninvasively assessed myocardial ischaemia; and the requirement and associated caveats of potent vasodilatory drugs to induce maximal vasodilatation of the coronary vascular bed.

  17. The development of radioactive sample surrogates for training and exercises

    Energy Technology Data Exchange (ETDEWEB)

    Martha Finck; Bevin Brush; Dick Jansen; David Chamberlain; Don Dry; George Brooks; Margaret Goldberg

    2012-03-01

    The development of radioactive sample surrogates for training and exercises Source term information is required for to reconstruct a device used in a dispersed radiological dispersal device. Simulating a radioactive environment to train and exercise sampling and sample characterization methods with suitable sample materials is a continued challenge. The Idaho National Laboratory has developed and permitted a Radioactive Response Training Range (RRTR), an 800 acre test range that is approved for open air dispersal of activated KBr, for training first responders in the entry and exit from radioactively contaminated areas, and testing protocols for environmental sampling and field characterization. Members from the Department of Defense, Law Enforcement, and the Department of Energy participated in the first contamination exercise that was conducted at the RRTR in the July 2011. The range was contaminated using a short lived radioactive Br-82 isotope (activated KBr). Soil samples contaminated with KBr (dispersed as a solution) and glass particles containing activated potassium bromide that emulated dispersed radioactive materials (such as ceramic-based sealed source materials) were collected to assess environmental sampling and characterization techniques. This presentation summarizes the performance of a radioactive materials surrogate for use as a training aide for nuclear forensics.

  18. Pan masala advertisements are surrogate for tobacco products.

    Science.gov (United States)

    Sushma, C; Sharang, C

    2005-01-01

    Pan masala is a comparatively recent habit in India and is marketed with and without tobacco. Advertisements of tobacco products have been banned in India since 1st May 2004. The advertisements of plain pan masala, which continue in Indian media, have been suspected to be surrogate for tobacco products bearing the same name. The study was carried out to assess whether these advertisements were for the intended product, or for tobacco products with same brand name. The programme of a popular television Hindi news channel was watched for a 24-h period. Programmes on the same channel and its English counterpart were watched on different days to assess whether the advertisements were repeated. The total duration of telecast of a popular brand of plain pan masala (Pan Parag) was multiplied by the rate charged by the channel to provide the cost of advertisement of this product. The total sale value of the company was multiplied by the proportion of usage of plain pan masala out of gutka plus pan masala habit as observed from a different study, to provide the annual sale value of plain pan masala product under reference. The annual sale value of plain Pan Parag was estimated to be Rs. 67.1 million. The annual cost of the advertisement of the same product on two television channels was estimated at Rs. 244.6 million. The advertisements of plain pan masala seen on Indian television are a surrogate for the tobacco products bearing the same name.

  19. Defining useful surrogates for user participation in online medical learning.

    LENUS (Irish Health Repository)

    Beddy, Peter

    2012-02-01

    "School for Surgeons" is a web-based distance learning program which provides online clinical-based tutorials to surgical trainees. Our aim was to determine surrogates of active participation and to assess the efficacy of methods to improve usage. Server logs of the 82 participants in the "School for Surgeons" were assessed for the two terms of the first year of the program. Data collected included total time online, mean session time, page requests, numbers of sessions online and the total number of assignments. An intervention regarding comparative peer usage patterns was delivered to the cohort between terms one and two. Of the 82 trainees enrolled, 83% (85% second term) logged into the program. Of all participants 88% (97% second term) submitted at least one assignment. Median submissions were four (eight second term) per trainee. Assignment submission closely correlated with number of sessions, total time online, downloads and page requests. Peer-based comparative feedback resulted in a significant increase in the number of assignments submitted (p < 0.01). Despite its recent introduction, "School for Surgeons" has a good participation rate. Assignment submission is a valid surrogate for usage. Students can be encouraged to move from passive observation to active participation in a virtual learning environment by providing structured comparative feedback ranking their performance.

  20. Proper Orthogonal Decomposition as Surrogate Model for Aerodynamic Optimization

    Directory of Open Access Journals (Sweden)

    Valentina Dolci

    2016-01-01

    Full Text Available A surrogate model based on the proper orthogonal decomposition is developed in order to enable fast and reliable evaluations of aerodynamic fields. The proposed method is applied to subsonic turbulent flows and the proper orthogonal decomposition is based on an ensemble of high-fidelity computations. For the construction of the ensemble, fractional and full factorial planes together with central composite design-of-experiment strategies are applied. For the continuous representation of the projection coefficients in the parameter space, response surface methods are employed. Three case studies are presented. In the first case, the boundary shape of the problem is deformed and the flow past a backward facing step with variable step slope is studied. In the second case, a two-dimensional flow past a NACA 0012 airfoil is considered and the surrogate model is constructed in the (Mach, angle of attack parameter space. In the last case, the aerodynamic optimization of an automotive shape is considered. The results demonstrate how a reduced-order model based on the proper orthogonal decomposition applied to a small number of high-fidelity solutions can be used to generate aerodynamic data with good accuracy at a low cost.

  1. Bayesian calibration of the Community Land Model using surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Ray, Jaideep; Hou, Zhangshuan; Huang, Maoyi; Swiler, Laura Painton

    2014-02-01

    We present results from the Bayesian calibration of hydrological parameters of the Community Land Model (CLM), which is often used in climate simulations and Earth system models. A statistical inverse problem is formulated for three hydrological parameters, conditional on observations of latent heat surface fluxes over 48 months. Our calibration method uses polynomial and Gaussian process surrogates of the CLM, and solves the parameter estimation problem using a Markov chain Monte Carlo sampler. Posterior probability densities for the parameters are developed for two sites with different soil and vegetation covers. Our method also allows us to examine the structural error in CLM under two error models. We find that surrogate models can be created for CLM in most cases. The posterior distributions are more predictive than the default parameter values in CLM. Climatologically averaging the observations does not modify the parameters' distributions significantly. The structural error model reveals a correlation time-scale which can be used to identify the physical process that could be contributing to it. While the calibrated CLM has a higher predictive skill, the calibration is under-dispersive.

  2. In vitro release control of ketoprofen from pH-sensitive gels consisting of poly(acryloyl- L-proline methyl ester) and saturated fatty acid sodium salts

    Science.gov (United States)

    Negishi, M.; Hiroki, A.; Miyajima, M.; Yoshida, M.; Asano, M.; Katakai, R.

    1999-06-01

    The effect of saturated fatty acid sodium salts (C n), sodium laurate (C 12), sodium myristate (C 14), sodium palmitate (C 16), and sodium stearate (C 18), on the swelling of poly(acryloyl- L-proline methyl ester) (A-ProOMe) gel was investigated in different pH solutions. The C n-loaded gels collapsed in a buffer solution with pH 3.0, while they expanded in a buffer solution with pH 6.5. This effect was strongly influenced by the number of methylene units in C n, as the threshold for causing this sensitivity existed between C 12 and C 14. On the other hand, a pulsatile release of ketoprofen occurred when the gel was cycled in buffer solutions between pH 3.0 and pH 6.5. This behavior may be attributable to the surface-regulated mechanism.

  3. 苯胺法制酮基布洛芬工艺改进%IMPROVEMENT ON SYNTHESIS OF KETOPROFEN FROM ANILINE

    Institute of Scientific and Technical Information of China (English)

    姜胜斌; 廖桂英; 袁华; 喻宗沅; 佘万能

    2001-01-01

    以苯胺为起始原料,经过酰胺化、环合、苄基化、水解、脱胺基、氧化等几步反应,得到产物酮基布洛芬,总收率42.5%。该法原料易得,反应条件温和,操作简单,收率较高,适合于工业化生产。%Ketoprofen was synthesized from anline by amidation, cyclization, benzylation, hydrolysis, deamination and oxidation with an overall yield of 42.5 %. This method has advantages of easy accessible raw materials, mild reaction conditions, convenient procedures, high yield and suitable to industrialization.

  4. Vertical Flume Testing of WIPP Surrogate Waste Materials

    Science.gov (United States)

    Herrick, C. G.; Schuhen, M.; Kicker, D.

    2013-12-01

    The Waste Isolation Pilot Plant (WIPP) is a U.S. Department of Energy geological repository for the permanent disposal of defense-related transuranic (TRU) waste. The waste is emplaced in rooms excavated in the bedded Salado salt formation at a depth of 655 m below ground surface. After emplacement of the waste, the repository will be sealed and decommissioned. The DOE demonstrates compliance with 40 CFR 194 by means of performance assessment (PA) calculations conducted by Sandia National Laboratories. WIPP PA calculations estimate the probability and consequences of radionuclide releases for a 10,000 year regulatory period. Human intrusion scenarios include cases in which a future borehole is drilled through the repository. Drilling mud flowing up the borehole will apply a hydrodynamic shear stress to the borehole wall which could result in erosion of the waste and radionuclides being carried up the borehole. WIPP PA uses the parameter TAUFAIL to represent the shear strength of the degraded waste. The hydrodynamic shear strength can only be measured experimentally by flume testing. Flume testing is typically performed horizontally, mimicking stream or ocean currents. However, in a WIPP intrusion event, the drill bit would penetrate the degraded waste and drilling mud would flow up the borehole in a predominantly vertical direction. In order to simulate this, a flume was designed and built so that the eroding fluid enters an enclosed vertical channel from the bottom and flows up past a specimen of surrogate waste material. The sample is pushed into the current by a piston attached to a step motor. A qualified data acquisition system controls and monitors the fluid's flow rate, temperature, pressure, and conductivity and the step motor's operation. The surrogate materials used correspond to a conservative estimate of degraded TRU waste at the end of the regulatory period. The recipes were previously developed by SNL based on anticipated future states of the waste

  5. Generic Selection Criteria for Safety and Patient Benefit [IV] - Physicochemical and pharmaceutical properties of brand-name and generic ketoprofen tapes.

    Science.gov (United States)

    Wada, Yuko; Kihara, Maki; Nozawa, Mitsuru; Shimokawa, Ken-Ichi; Ishii, Fumiyoshi

    2015-06-01

    The physicochemical and pharmaceutical properties (pH, peel force, water-vapor permeability, and stretchability) of brand-name and generic ketoprofen products were evaluated and compared. The pHs of Mohrus as a brand-name product and Teikoku as a generic product were low (about 4). Among the other generic products, Patell and Nichi-Iko had a pH of about 4.3 while Frestol, Raynanon, BMD, and Touchron showed a pH of 4.6-5.2, which was in the pH range of normal healthy skin (4.5-6.5). The adhesive force was high (≥ 1.38) for Mohrus as a brand-name product as well as for Teikoku and Patell as generic products, but it was low (≤ 0.57) for the other 5 generic products. The water-vapor permeabilities of Mohrus as a brand-name product and Teikoku and Patell as generic products were low, being less than 1/6 of those for the other 5 generic products. Among the 5 generic products, BMD showed the highest water-vapor permeability (1,330 g/m²), and the other products also showed a value ≥ 1,100 g/m². The elongatedness of Mohrus was the lowest (15.5 cm), and that of Raynanon was the highest (24.5 cm); the difference was 9 cm. In this study, the physiochemical and pharmaceutical properties of ketoprofen tapes were clarified, which will allow pharmacists to provide products according to the needs of each patient when a brand-name product is changed to a generic one.

  6. Pharmacokinetics of ketoprofen absorption in rat intestines%酮洛芬大鼠在体肠吸收药物动力学研究

    Institute of Scientific and Technical Information of China (English)

    李彩艳; 任小军

    2016-01-01

    目的 考察酮洛芬在大鼠各肠段的吸收动力学特征.方法 采用大鼠在体单向灌流法进行肠吸收实验,利用高效液相色谱法(HPLC)测定酮洛芬的含量,从药物浓度、吸收部位、灌流速度3个方面考察酮洛芬的各肠段吸收动力学特征,利用质量法计算动力学参数.结果 酮洛芬浓度在1.4~9.8 mg/L范围内,吸收速率常数Ka和表观吸收系数Papp值差异无统计学意义(P>0.05);小肠段和结肠段的Ka和Papp值差异有统计学意义(P0.05);不同灌流速度下,Ka和Papp值差异有统计学意义(P0.05). The Ka and Papp were statistically different between small intestine and colon segments (P0.05). Different perfusion rates were associated with statistically different values of Ka and Papp (P<0.05). Conclusion Ketoprofen is absorbed into the systemic circulation mainly via passive diffusion. Good performance of ketoprofen absorption is found in whole intestinal segments. With increasing perfusion rate, Ka and Papp values are significantly increased.

  7. 酮洛芬对映异构体的计算机模拟%Computer Simulation Study on the Enantiomers of Ketoprofen

    Institute of Scientific and Technical Information of China (English)

    洪礼乐; 张文成; 任少伟; 李兵; 董秀丽

    2014-01-01

    The optimal geometry configurations, energies of Ketoprofenwere simulated by Hyperchem8.0 software, the results indicated that the energy of S-Ketoprofenslightly below the R-Ketoprofen energy. A molecular simulation method for molecularly imprinted polymerization system using S-Ketoprofen as template and 4-vinyl pyridine (4-VP),methacrylicacid (MAA) and acrylicamide (AM) as functional monomers was presented. The optimal geometry configuration, energy, reaction ratio and binding energy of thepre-polymerization systems were simulated by a semi-empirical method (PM3) and Amber MM methods with Hyperchem8.0 software. The results show that MAA gives stronger bonding interaction with S-Ketoprofethan other monomer molecules studied. The model with good stability and predictability, and it provided valuable basic data for designing and optimizing treatment process.%采用Hyperchem8.0计算酮洛芬对映异构体的分子结构及能量,证明(S)-布洛芬的能量比(R)-酮洛芬略低。以(S)-酮洛芬为模板分子,4-乙烯吡啶(4-VP)、丙烯酰胺(AM)及α-甲基丙烯酸(MAA)为功能单体,模拟及探讨不同功能单体对酮洛芬的结合能,结果显示4-VP与模板分子所形成复合物的结合能较AM略大,模型稳定性和预测能力俱佳,为混旋酮洛芬的拆分打下了理论基础。

  8. Comparison of the anti-inflammatory actions of flunixin and ketoprofen in horses applying PK/PD modelling.

    Science.gov (United States)

    Landoni, M F; Lees, P

    1995-07-01

    A comparative study in horses of the pharmacokinetics (PK) and pharmacodynamics (PD) of 2 extensively used nonsteroidal anti-inflammatory drugs (NSAIDs), flunixin (FXN) and ketoprofen (KTP), was carried out applying PK/PD modelling. To evaluate the anti-inflammatory properties of these drugs a model of acute inflammation, comprising surgically implanted subcutaneous tissue cages stimulated by intracaveal injection of carrageenan, was used. FXN elimination half-life (T1/2 beta) in plasma was 3.37 +/- 1.09 h. However, in exudate a much longer T1/2 beta was obtained (15.99 +/- 3.80 h). Apparent volume of distribution (Vdarea) for FXN was 0.317 +/- 0.126 l/kg and body clearance (ClB) was 0.058 +/- 0.004 l/kg/h. KTP displayed enantioselective pharmacokinetics, the S(+) enantiomer being predominant in plasma, exudate and transudate. T1/2 beta values for R(-) and S(+)KTP were, respectively, 1.09 +/- 0.19 h and 1.51 +/- 0.45 h (plasma) and 19.73 +/- 2.72 h and 22.64 +/- 4.34 h (exudate), respectively. R(-)KTP was cleared more rapidly than the S(+) enantiomer. ClB values were 0.277 +/- 0.035 l/kg/h and 0.202 +/- 0.022 l/kg/h, respectively. FXN and KTP pharmacodynamics was evaluated by determining their inhibitory effects on serum thromboxane (Tx)B2, exudate prostaglandin (PG)E2, leukotriene (LT)B4 and beta-glucuronidase (beta-glu) and intradermal bradykinin-induced swelling. Both drugs produced marked inhibition of serum TxB2 synthesis for up to 24 h, with no significant differences between the drugs. FXN was a more potent inhibitor of exudate PGE2, the EC50 for FXN being lower (P < 0.01) than that for KTP (0.019 +/- 0.010 microgram/ml and 0.057 +/- 0.009 microgram/ml, respectively). Neither drug had any effect on exudate LTB4 concentration. Differences between the 2 drugs were observed for the inhibition of beta-glu, the Emax for KTP being higher (P < 0.01) than for FXN. However, no differences were observed in other PD parameters. Both FXN and KTP inhibited bradykinin

  9. A review of selection-based tests of abiotic surrogates for species representation.

    Science.gov (United States)

    Beier, Paul; Sutcliffe, Patricia; Hjort, Jan; Faith, Daniel P; Pressey, Robert L; Albuquerque, Fabio

    2015-06-01

    Because conservation planners typically lack data on where species occur, environmental surrogates--including geophysical settings and climate types--have been used to prioritize sites within a planning area. We reviewed 622 evaluations of the effectiveness of abiotic surrogates in representing species in 19 study areas. Sites selected using abiotic surrogates represented more species than an equal number of randomly selected sites in 43% of tests (55% for plants) and on average improved on random selection of sites by about 8% (21% for plants). Environmental diversity (ED) (42% median improvement on random selection) and biotically informed clusters showed promising results and merit additional testing. We suggest 4 ways to improve performance of abiotic surrogates. First, analysts should consider a broad spectrum of candidate variables to define surrogates, including rarely used variables related to geographic separation, distance from coast, hydrology, and within-site abiotic diversity. Second, abiotic surrogates should be defined at fine thematic resolution. Third, sites (the landscape units prioritized within a planning area) should be small enough to ensure that surrogates reflect species' environments and to produce prioritizations that match the spatial resolution of conservation decisions. Fourth, if species inventories are available for some planning units, planners should define surrogates based on the abiotic variables that most influence species turnover in the planning area. Although species inventories increase the cost of using abiotic surrogates, a modest number of inventories could provide the data needed to select variables and evaluate surrogates. Additional tests of nonclimate abiotic surrogates are needed to evaluate the utility of conserving nature's stage as a strategy for conservation planning in the face of climate change. © 2015 Society for Conservation Biology.

  10. Single dose dipyrone for acute postoperative pain.

    Science.gov (United States)

    Edwards, Jayne; Meseguer, Fuensanta; Faura, Clara; Moore, R Andrew; McQuay, Henry J; Derry, Sheena

    2010-09-08

    Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought. To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain. The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010. Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs. Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected. Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls.Over 70% of participants experienced at least 50% pain relief over 4 to 6 hours with oral dipyrone 500 mg compared to 30

  11. Top predators: hot or not? A call for systematic assessment of biodiversity surrogates

    NARCIS (Netherlands)

    Cabeza, M.; Arponen, A.; Teeffelen, van A.J.A.

    2008-01-01

    argue that top predators are justified conservation surrogates based on a case study where raptor presence is associated with high species richness of birds, butterflies and trees. 2. We question the methodology as well as the applicability of their results, and clarify differences between surrogate

  12. Comparison of surrogate models with different methods in groundwater remediation process

    Indian Academy of Sciences (India)

    Jiannan Luo; Wenxi Lu

    2014-10-01

    Surrogate modelling is an effective tool for reducing computational burden of simulation optimization. In this article, polynomial regression (PR), radial basis function artificial neural network (RBFANN), and kriging methods were compared for building surrogate models of a multiphase flow simulation model in a simplified nitrobenzene contaminated aquifer remediation problem. In the model accuracy analysis process, a 10-fold cross validation method was adopted to evaluate the approximation accuracy of the three surrogate models. The results demonstrated that: RBFANN surrogate model and kriging surrogate model had acceptable approximation accuracy, and further that kriging model’s approximation accuracy was slightly higher than RBFANN model. However, the PR model demonstrated unacceptably poor approximation accuracy. Therefore, the RBFANN and kriging surrogates were selected and used in the optimization process to identify the most cost-effective remediation strategy at a nitrobenzene-contaminated site. The optimal remediation costs obtained with the two surrogate-based optimization models were similar, and had similar computational burden. These two surrogate-based optimization models are efficient tools for optimal groundwater remediation strategy identification.

  13. Someone to Lean on: Assessment and Implications of Social Surrogate Use in Childhood

    Science.gov (United States)

    Arbeau, Kimberley A.; Coplan, Robert J.; Matheson, Adrienne

    2012-01-01

    A social surrogate is a person who helps a shy individual deal with the stresses of a social situation. Previous research has only investigated social surrogate use in adults. The purpose of the current study was to develop and evaluate a new self-report measure of social surrogacy in middle childhood and to explore the implications of this…

  14. Critical review of norovirus surrogates in food safety research: rationale for considering volunteer studies

    Science.gov (United States)

    The inability to propagate human norovirus (NoV) or to clearly differentiate infectious from noninfectious virus particles have led to the use of surrogate viruses, like feline calicivirus (FCV) and murine norovirus-1 (MNV), which are propagatable in cell culture. The use of surrogates is predicate...

  15. Somatic coliphages as surrogates for enteroviruses in sludge hygienization treatments.

    Science.gov (United States)

    Martín-Díaz, Julia; Casas-Mangas, Raquel; García-Aljaro, Cristina; Blanch, Anicet R; Lucena, Francisco

    2016-01-01

    Conventional bacterial indicators present serious drawbacks giving information about viral pathogens persistence during sludge hygienization treatments. This calls for the search of alternative viral indicators. Somatic coliphages' (SOMCPH) ability for acting as surrogates for enteroviruses was assessed in 47 sludge samples subjected to novel treatment processes. SOMCPH, infectious enteroviruses and genome copies of enteroviruses were monitored. Only one of these groups, the bacteriophages, was present in the sludge at concentrations that allowed the evaluation of treatment's performance. An indicator/pathogen relationship of 4 log10 (PFU/g dw) was found between SOMCPH and infective enteroviruses and their detection accuracy was assessed. The obtained results and the existence of rapid and standardized methods encourage the inclusion of SOMCPH quantification in future sludge directives. In addition, an existing real-time quantitative polymerase chain reaction (RT-qPCR) for enteroviruses was adapted and applied.

  16. A Rigorous Framework for Optimization of Expensive Functions by Surrogates

    Science.gov (United States)

    Booker, Andrew J.; Dennis, J. E., Jr.; Frank, Paul D.; Serafini, David B.; Torczon, Virginia; Trosset, Michael W.

    1998-01-01

    The goal of the research reported here is to develop rigorous optimization algorithms to apply to some engineering design problems for which design application of traditional optimization approaches is not practical. This paper presents and analyzes a framework for generating a sequence of approximations to the objective function and managing the use of these approximations as surrogates for optimization. The result is to obtain convergence to a minimizer of an expensive objective function subject to simple constraints. The approach is widely applicable because it does not require, or even explicitly approximate, derivatives of the objective. Numerical results are presented for a 31-variable helicopter rotor blade design example and for a standard optimization test example.

  17. Sparse polynomial surrogates for aerodynamic computations with random inputs

    CERN Document Server

    Savin, Eric; Peter, Jacques

    2015-01-01

    This paper deals with some of the methodologies used to construct polynomial surrogate models based on generalized polynomial chaos (gPC) expansions for applications to uncertainty quantification (UQ) in aerodynamic computations. A core ingredient in gPC expansions is the choice of a dedicated sampling strategy, so as to define the most significant scenarios to be considered for the construction of such metamodels. A desirable feature of the proposed rules shall be their ability to handle several random inputs simultaneously. Methods to identify the relative "importance" of those variables or uncertain data shall be ideally considered as well. The present work is more particularly dedicated to the development of sampling strategies based on sparsity principles. Sparse multi-dimensional cubature rules based on general one-dimensional Gauss-Jacobi-type quadratures are first addressed. These sets are non nested, but they are well adapted to the probability density functions with compact support for the random in...

  18. High-Temperature Oxidation of Plutonium Surrogate Metals and Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Sparks, Joshua C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Krantz, Kelsie E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Christian, Jonathan H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Washington, II, Aaron L. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-07-27

    The Plutonium Management and Disposition Agreement (PMDA) is a nuclear non-proliferation agreement designed to remove 34 tons of weapons-grade plutonium from Russia and the United States. While several removal options have been proposed since the agreement was first signed in 2000, processing the weapons-grade plutonium to mixed-oxide (MOX) fuel has remained the leading candidate for achieving the goals of the PMDA. However, the MOX program has received its share of criticisms, which causes its future to be uncertain. One alternative pathway for plutonium disposition would involve oxidizing the metal followed by impurity down blending and burial in the Waste Isolation Pilot Plant (WIPP) in Carlsbad, New Mexico. This pathway was investigated by use of a hybrid microwave and a muffle furnace with Fe and Al as surrogate materials. Oxidation occurred similarly in the microwave and muffle furnace; however, the microwave process time was significantly faster.

  19. Protein prosthesis: β-peptides as reverse-turn surrogates.

    Science.gov (United States)

    Arnold, Ulrich; Huck, Bayard R; Gellman, Samuel H; Raines, Ronald T

    2013-03-01

    The introduction of non-natural modules could provide unprecedented control over folding/unfolding behavior, conformational stability, and biological function of proteins. Success requires the interrogation of candidate modules in natural contexts. Here, expressed protein ligation is used to replace a reverse turn in bovine pancreatic ribonuclease (RNase A) with a synthetic β-dipeptide: β²-homoalanine-β³-homoalanine. This segment is known to adopt an unnatural reverse-turn conformation that contains a 10-membered ring hydrogen bond, but one with a donor-acceptor pattern opposite to that in the 10-membered rings of natural reverse turns. The RNase A variant has intact enzymatic activity, but unfolds more quickly and has diminished conformational stability relative to native RNase A. These data indicate that hydrogen-bonding pattern merits careful consideration in the selection of beneficial reverse-turn surrogates. Copyright © 2012 The Protein Society.

  20. Argan oil improves surrogate markers of CVD in humans.

    Science.gov (United States)

    Sour, Souad; Belarbi, Meriem; Khaldi, Darine; Benmansour, Nassima; Sari, Nassima; Nani, Abdelhafid; Chemat, Farid; Visioli, Francesco

    2012-06-01

    Limited - though increasing - evidence suggests that argan oil might be endowed with potential healthful properties, mostly in the areas of CVD and prostate cancer. We sought to comprehensively determine the effects of argan oil supplementation on the plasma lipid profile and antioxidant status of a group of healthy Algerian subjects, compared with matched controls. A total of twenty healthy subjects consumed 15 g/d of argan oil - with toasted bread - for breakfast, during 4 weeks (intervention group), whereas twenty matched controls followed their habitual diet, but did not consume argan oil. The study lasted 30 d. At the end of the study, argan oil-supplemented subjects exhibited higher plasma vitamin E concentrations, lower total and LDL-cholesterol, lower TAG and improved plasma and cellular antioxidant profile, when compared with controls. In conclusion, we showed that Algerian argan oil is able to positively modulate some surrogate markers of CVD, through mechanisms which warrant further investigation.

  1. Cholesterol paradox: a correlate does not a surrogate make.

    Science.gov (United States)

    DuBroff, Robert

    2017-03-01

    The global campaign to lower cholesterol by diet and drugs has failed to thwart the developing pandemic of coronary heart disease around the world. Some experts believe this failure is due to the explosive rise in obesity and diabetes, but it is equally plausible that the cholesterol hypothesis, which posits that lowering cholesterol prevents cardiovascular disease, is incorrect. The recently presented ACCELERATE trial dumbfounded many experts by failing to demonstrate any cardiovascular benefit of evacetrapib despite dramatically lowering low-density lipoprotein cholesterol and raising high-density lipoprotein cholesterol in high-risk patients with coronary disease. This clinical trial adds to a growing volume of knowledge that challenges the validity of the cholesterol hypothesis and the utility of cholesterol as a surrogate end point. Inadvertently, the cholesterol hypothesis may have even contributed to this pandemic. This perspective critically reviews this evidence and our reluctance to acknowledge contradictory information.

  2. Technological advances in suspended-sediment surrogate monitoring

    Science.gov (United States)

    Gray, John R.; Gartner, Jeffrey W.

    2009-01-01

    Surrogate technologies to continuously monitor suspended sediment show promise toward supplanting traditional data collection methods requiring routine collection and analysis of water samples. Commercially available instruments operating on bulk optic (turbidity), laser optic, pressure difference, and acoustic backscatter principles are evaluated based on cost, reliability, robustness, accuracy, sample volume, susceptibility to biological fouling, and suitable range of mass concentration and particle size distribution. In situ turbidimeters are widely used. They provide reliable data where the point measurements can be reliably correlated to the river's mean cross section concentration value, effects of biological fouling can be minimized, and concentrations remain below the sensor's upper measurement limit. In situ laser diffraction instruments have similar limitations and can cost 6 times the approximate $5000 purchase price of a turbidimeter. However, laser diffraction instruments provide volumetric-concentration data in 32 size classes. Pressure differential instruments measure mass density in a water column, thus integrating substantially more streamflow than a point measurement. They are designed for monitoring medium-to-large concentrations, are generally unaffected by biological fouling, and cost about the same as a turbidimeter. However, their performance has been marginal in field applications. Acoustic Doppler profilers use acoustic backscatter to measure suspended sediment concentrations in orders of magnitude more streamflow than do instruments that rely on point measurements. The technology is relatively robust and generally immune to effects of biological fouling. Cost of a single-frequency device is about double that of a turbidimeter. Multifrequency arrays also provide the potential to resolve concentrations by clay silt versus sand size fractions. Multifrequency hydroacoustics shows the most promise for revolutionizing collection of continuous

  3. Effectiveness of chitosan on the inactivation of enteric viral surrogates.

    Science.gov (United States)

    Davis, Robert; Zivanovic, Svetlana; D'Souza, Doris H; Davidson, P Michael

    2012-10-01

    Chitosan is known to have bactericidal and antifungal activity. Although human noroviruses are the leading cause of non-bacterial gastroenteritis, information on the efficacy of chitosan against foodborne viruses is very limited. The objective of this work was to determine the effectiveness of different molecular weight chitosans against the cultivable human norovirus and enteric virus surrogates, feline calicivirus, FCV-F9, murine norovirus, MNV-1, and bacteriophages, MS2 and phiX174. Five purified chitosans (53, 222, 307, 421, ~1150 kDa) were dissolved in water, 1% acetic acid, or aqueous HCl pH = 4.3, sterilized by membrane filtration, and mixed with equal volume of virus to obtain a final concentration of 0.7% chitosan and 5 log(10) PFU/ml virus. Virus-chitosan suspensions were incubated for 3 h at 37 °C. Untreated viruses in PBS, in PBS with acetic acid, and in PBS with HCl were tested as controls. Each experiment was run in duplicate and replicated at least twice. Water-soluble chitosan (53 kDa) reduced phiX174, MS2, FCV-F9 and MNV-1 titers by 0.59, 2.44, 3.36, and 0.34 log(10) PFU/ml respectively. Chitosans in acetic acid decreased phiX174 by 1.19-1.29, MS2 by 1.88-5.37, FCV-F9 by 2.27-2.94, and MNV-1 by 0.09-0.28 log(10) PFU/ml, respectively. Increasing the MW of chitosan corresponded with an increasing antiviral effect on MS2, but did not appear to play a role for the other three tested viral surrogates. Overall, chitosan treatments showed the greatest reduction for FCV-F9, and MS2 followed by phiX174, and with no significant effect on MNV-1.

  4. Potential cryptosporidium surrogates and evaluation of compressible oocysts

    Energy Technology Data Exchange (ETDEWEB)

    Li, S.Y.; Goodrich, J.A.; Owens, J.H. [Environmental Protection Agency, Cincinnati, OH (United States)] [and others

    1995-10-01

    Cryptosporidium has been recognized as an important waterborne agent of gastroenteritis and a biological contaminant in drinking water. The widespread presence of Cryptosporidium in surface source water and either untreated or insufficiently treated drinking water has led to Cryptosporidium outbreaks in the United States and worldwide. Among the conventional control practices, filtration and high temperature distillation appear to be the potentially viable technologies for protection against Cryptosporidium in drinking water. As employed in many water plants, filtration is likely to be the most practical treatment technology utilized for Cryptosporidium removal in the near future. Consequently, accurate and reliable methods for evaluation of Cryptosporidium removal rates for filtration-based systems are necessary to assist States in determining drinking water quality and complying with the up-coming national standard for Cryptosporidium in drinking water. Furthermore, searching for reliable and non-hazardous surrogates for evaluation of treatment plant efficiency has been intensified because of the potential health risk associated with Cryptosporidium. Additionally, during the filtration procedure Cryptosporidium may squeeze and fold through pores size of the filtration systems that are smaller than the diameter of the organism; a fraction of these Cryptosporidium oocysts may still remain a certain degree of viability. These uncertainties are critical for the evaluation and optimization of filtration-based physical treatment systems. The in-house research studies described below consist of two parts. One is a potential surrogate study using bag filtration systems at the US EPA Test & Evaluation Facility in Cincinnati, Ohio. The second is Cryptosporidium compressibility and viability investigation.

  5. Surrogate-assisted feature extraction for high-throughput phenotyping.

    Science.gov (United States)

    Yu, Sheng; Chakrabortty, Abhishek; Liao, Katherine P; Cai, Tianrun; Ananthakrishnan, Ashwin N; Gainer, Vivian S; Churchill, Susanne E; Szolovits, Peter; Murphy, Shawn N; Kohane, Isaac S; Cai, Tianxi

    2017-04-01

    Phenotyping algorithms are capable of accurately identifying patients with specific phenotypes from within electronic medical records systems. However, developing phenotyping algorithms in a scalable way remains a challenge due to the extensive human resources required. This paper introduces a high-throughput unsupervised feature selection method, which improves the robustness and scalability of electronic medical record phenotyping without compromising its accuracy. The proposed Surrogate-Assisted Feature Extraction (SAFE) method selects candidate features from a pool of comprehensive medical concepts found in publicly available knowledge sources. The target phenotype's International Classification of Diseases, Ninth Revision and natural language processing counts, acting as noisy surrogates to the gold-standard labels, are used to create silver-standard labels. Candidate features highly predictive of the silver-standard labels are selected as the final features. Algorithms were trained to identify patients with coronary artery disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis using various numbers of labels to compare the performance of features selected by SAFE, a previously published automated feature extraction for phenotyping procedure, and domain experts. The out-of-sample area under the receiver operating characteristic curve and F -score from SAFE algorithms were remarkably higher than those from the other two, especially at small label sizes. SAFE advances high-throughput phenotyping methods by automatically selecting a succinct set of informative features for algorithm training, which in turn reduces overfitting and the needed number of gold-standard labels. SAFE also potentially identifies important features missed by automated feature extraction for phenotyping or experts.

  6. Pan masala advertisements are surrogate for tobacco products

    Directory of Open Access Journals (Sweden)

    Sushma C

    2005-01-01

    Full Text Available BACKGROUND: Pan masala is a comparatively recent habit in India and is marketed with and without tobacco. Advertisements of tobacco products have been banned in India since 1st May 2004. The advertisements of plain pan masala, which continue in Indian media, have been suspected to be surrogate for tobacco products bearing the same name. The study was carried out to assess whether these advertisements were for the intended product, or for tobacco products with same brand name. MATERIALS AND METHODS: The programme of a popular television Hindi news channel was watched for a 24-h period. Programmes on the same channel and its English counterpart were watched on different days to assess whether the advertisements were repeated. The total duration of telecast of a popular brand of plain pan masala (Pan Parag was multiplied by the rate charged by the channel to provide the cost of advertisement of this product. The total sale value of the company was multiplied by the proportion of usage of plain pan masala out of gutka plus pan masala habit as observed from a different study, to provide the annual sale value of plain pan masala product under reference. RESULTS: The annual sale value of plain Pan Parag was estimated to be Rs. 67.1 million. The annual cost of the advertisement of the same product on two television channels was estimated at Rs. 244.6 million. CONCLUSION: The advertisements of plain pan masala seen on Indian television are a surrogate for the tobacco products bearing the same name.

  7. Antiviral Effects of Lactococcus lactis on Feline Calicivirus, A Human Norovirus Surrogate.

    Science.gov (United States)

    Aboubakr, Hamada A; El-Banna, Amr A; Youssef, Mohammed M; Al-Sohaimy, Sobhy A A; Goyal, Sagar M

    2014-12-01

    Foodborne viruses, particularly human norovirus (NV) and hepatitis virus type A, are a cause of concern for public health making it necessary to explore novel and effective techniques for prevention of foodborne viral contamination, especially in minimally processed and ready-to-eat foods. This study aimed to determine the antiviral activity of a probiotic lactic acid bacterium (LAB) against feline calicivirus (FCV), a surrogate of human NV. Bacterial growth medium filtrate (BGMF) of Lactococcus lactis subsp. lactis LM0230 and its bacterial cell suspension (BCS) were evaluated separately for their antiviral activity against FCV grown in Crandell-Reese feline kidney (CRFK) cells. No significant antiviral effect was seen when CRFK cells were pre-treated with either BGMF (raw or pH 7-adjusted BGMF) or BCS. However, pre-treatment of FCV with BGMF and BCS resulted in a reduction in virus titers of 1.3 log10 tissue culture infectious dose (TCID)50 and 1.8 log10 TCID50, respectively. The highest reductions in FCV infectivity were obtained when CRFK cells were co-treated with FCV and pH 7-adjusted BGMF or with FCV and BCS (7.5 log10 TCID50 and 6.0 log10 TCID50, respectively). These preliminary results are encouraging and indicate the need for continued studies on the role of probiotics and LAB on inactivation of viruses in various types of foods.

  8. Learning image based surrogate relevance criterion for atlas selection in segmentation

    Science.gov (United States)

    Zhao, Tingting; Ruan, Dan

    2016-06-01

    Picking geometrically relevant atlases from the whole training set is crucial to multi-atlas based image segmentation, especially with extensive data of heterogeneous quality in the Big Data era. Unfortunately, there is very limited understanding of how currently used image similarity criteria reveal geometric relevance, let alone the optimization of them. This paper aims to develop a good image based surrogate relevance criterion to best reflect the underlying inaccessible geometric relevance in a learning context. We cast this surrogate learning problem into an optimization framework, by encouraging the image based surrogate to behave consistently with geometric relevance during training. In particular, we desire a criterion to be small for image pairs with similar geometry and large for those with significantly different segmentation geometry. Validation experiments on corpus callosum segmentation demonstrate the improved quality of the learned surrogate compared to benchmark surrogate candidates.

  9. A computational methodology for formulating gasoline surrogate fuels with accurate physical and chemical kinetic properties

    KAUST Repository

    Ahmed, Ahfaz

    2015-03-01

    Gasoline is the most widely used fuel for light duty automobile transportation, but its molecular complexity makes it intractable to experimentally and computationally study the fundamental combustion properties. Therefore, surrogate fuels with a simpler molecular composition that represent real fuel behavior in one or more aspects are needed to enable repeatable experimental and computational combustion investigations. This study presents a novel computational methodology for formulating surrogates for FACE (fuels for advanced combustion engines) gasolines A and C by combining regression modeling with physical and chemical kinetics simulations. The computational methodology integrates simulation tools executed across different software platforms. Initially, the palette of surrogate species and carbon types for the target fuels were determined from a detailed hydrocarbon analysis (DHA). A regression algorithm implemented in MATLAB was linked to REFPROP for simulation of distillation curves and calculation of physical properties of surrogate compositions. The MATLAB code generates a surrogate composition at each iteration, which is then used to automatically generate CHEMKIN input files that are submitted to homogeneous batch reactor simulations for prediction of research octane number (RON). The regression algorithm determines the optimal surrogate composition to match the fuel properties of FACE A and C gasoline, specifically hydrogen/carbon (H/C) ratio, density, distillation characteristics, carbon types, and RON. The optimal surrogate fuel compositions obtained using the present computational approach was compared to the real fuel properties, as well as with surrogate compositions available in the literature. Experiments were conducted within a Cooperative Fuels Research (CFR) engine operating under controlled autoignition (CAI) mode to compare the formulated surrogates against the real fuels. Carbon monoxide measurements indicated that the proposed surrogates

  10. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    DEFF Research Database (Denmark)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

    2007-01-01

    of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery...... endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation...

  11. Laboratory Testing of Waste Isolation Pilot Plant Surrogate Waste Materials

    Science.gov (United States)

    Broome, S.; Bronowski, D.; Pfeifle, T.; Herrick, C. G.

    2011-12-01

    The Waste Isolation Pilot Plant (WIPP) is a U.S. Department of Energy geological repository for the permanent disposal of defense-related transuranic (TRU) waste. The waste is emplaced in rooms excavated in the bedded Salado salt formation at a depth of 655 m below the ground surface. After emplacement of the waste, the repository will be sealed and decommissioned. WIPP Performance Assessment modeling of the underground material response requires a full and accurate understanding of coupled mechanical, hydrological, and geochemical processes and how they evolve with time. This study was part of a broader test program focused on room closure, specifically the compaction behavior of waste and the constitutive relations to model this behavior. The goal of this study was to develop an improved waste constitutive model. The model parameters are developed based on a well designed set of test data. The constitutive model will then be used to realistically model evolution of the underground and to better understand the impacts on repository performance. The present study results are focused on laboratory testing of surrogate waste materials. The surrogate wastes correspond to a conservative estimate of the degraded containers and TRU waste materials after the 10,000 year regulatory period. Testing consists of hydrostatic, uniaxial, and triaxial tests performed on surrogate waste recipes that were previously developed by Hansen et al. (1997). These recipes can be divided into materials that simulate 50% and 100% degraded waste by weight. The percent degradation indicates the anticipated amount of iron corrosion, as well as the decomposition of cellulosics, plastics, and rubbers. Axial, lateral, and volumetric strain and axial and lateral stress measurements were made. Two unique testing techniques were developed during the course of the experimental program. The first involves the use of dilatometry to measure sample volumetric strain under a hydrostatic condition. Bulk

  12. A general framework to learn surrogate relevance criterion for atlas based image segmentation

    Science.gov (United States)

    Zhao, Tingting; Ruan, Dan

    2016-09-01

    Multi-atlas based image segmentation sees great opportunities in the big data era but also faces unprecedented challenges in identifying positive contributors from extensive heterogeneous data. To assess data relevance, image similarity criteria based on various image features widely serve as surrogates for the inaccessible geometric agreement criteria. This paper proposes a general framework to learn image based surrogate relevance criteria to better mimic the behaviors of segmentation based oracle geometric relevance. The validity of its general rationale is verified in the specific context of fusion set selection for image segmentation. More specifically, we first present a unified formulation for surrogate relevance criteria and model the neighborhood relationship among atlases based on the oracle relevance knowledge. Surrogates are then trained to be small for geometrically relevant neighbors and large for irrelevant remotes to the given targets. The proposed surrogate learning framework is verified in corpus callosum segmentation. The learned surrogates demonstrate superiority in inferring the underlying oracle value and selecting relevant fusion set, compared to benchmark surrogates.

  13. Surrogate mobility and orientation affect the early neurobehavioral development of infant rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Dettmer, Amanda M; Ruggiero, Angela M; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J

    2008-05-01

    A biological mother's movement appears necessary for optimal development in infant monkeys. However, nursery-reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard stationary rocking surrogates (RS) and to 9-15 infants reared with their biological mothers (MR) for early developmental outcome. We predicted that MS infants would develop more similarly to MR infants than RS infants. In neonatal assessments conducted at Day 30, both MS and MR infants showed more highly developed motor activity than RS infants on measures of grasping (p = .009), coordination (p = .038), spontaneous crawl (p = .009), and balance (p = .003). At 2-3 months of age, both MS and MR infants displayed higher levels of exploration in the home cage than RS infants (p = .016). In a novel situation in which only MS and RS infants were tested, MS infants spent less time near their surrogates in the first five minutes of the test session than RS infants (p = .05), indicating a higher level of comfort. Collectively, these results suggest that when nursery-rearing of infant monkeys is necessary, a mobile hanging surrogate may encourage more normative development of gross motor skills and exploratory behavior and may serve as a useful alternative to stationary or rocking surrogates.

  14. A general framework to learn surrogate relevance criterion for atlas based image segmentation.

    Science.gov (United States)

    Zhao, Tingting; Ruan, Dan

    2016-09-07

    Multi-atlas based image segmentation sees great opportunities in the big data era but also faces unprecedented challenges in identifying positive contributors from extensive heterogeneous data. To assess data relevance, image similarity criteria based on various image features widely serve as surrogates for the inaccessible geometric agreement criteria. This paper proposes a general framework to learn image based surrogate relevance criteria to better mimic the behaviors of segmentation based oracle geometric relevance. The validity of its general rationale is verified in the specific context of fusion set selection for image segmentation. More specifically, we first present a unified formulation for surrogate relevance criteria and model the neighborhood relationship among atlases based on the oracle relevance knowledge. Surrogates are then trained to be small for geometrically relevant neighbors and large for irrelevant remotes to the given targets. The proposed surrogate learning framework is verified in corpus callosum segmentation. The learned surrogates demonstrate superiority in inferring the underlying oracle value and selecting relevant fusion set, compared to benchmark surrogates.

  15. A linear programming model for optimizing HDR brachytherapy dose distributions with respect to mean dose in the DVH-tail

    Energy Technology Data Exchange (ETDEWEB)

    Holm, Åsa; Larsson, Torbjörn [Department of Mathematics, Linköping University, SE-581 83 Linköping (Sweden); Tedgren, Åsa Carlsson [Department of Medical and Health Sciences, Radiation Physics, Linköping University, SE 581-83 Linköping, Sweden and Swedish Radiation Safety Authority, SE-171 16 Stockholm (Sweden)

    2013-08-15

    Purpose: Recent research has shown that the optimization model hitherto used in high-dose-rate (HDR) brachytherapy corresponds weakly to the dosimetric indices used to evaluate the quality of a dose distribution. Although alternative models that explicitly include such dosimetric indices have been presented, the inclusion of the dosimetric indices explicitly yields intractable models. The purpose of this paper is to develop a model for optimizing dosimetric indices that is easier to solve than those proposed earlier.Methods: In this paper, the authors present an alternative approach for optimizing dose distributions for HDR brachytherapy where dosimetric indices are taken into account through surrogates based on the conditional value-at-risk concept. This yields a linear optimization model that is easy to solve, and has the advantage that the constraints are easy to interpret and modify to obtain satisfactory dose distributions.Results: The authors show by experimental comparisons, carried out retrospectively for a set of prostate cancer patients, that their proposed model corresponds well with constraining dosimetric indices. All modifications of the parameters in the authors' model yield the expected result. The dose distributions generated are also comparable to those generated by the standard model with respect to the dosimetric indices that are used for evaluating quality.Conclusions: The authors' new model is a viable surrogate to optimizing dosimetric indices and quickly and easily yields high quality dose distributions.

  16. Results from Second Round of Remediated Nitrate Salt Surrogate Formulation and Testing

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Geoffrey Wayne [Los Alamos National Laboratory; Leonard, Philip [Los Alamos National Laboratory; Hartline, Ernest Leon [Los Alamos National Laboratory; Tian, Hongzhao [Los Alamos National Laboratory

    2016-04-04

    High Explosives and Technology (M-7) completed the second round of formulation and testing of Remediated Nitrate Salt (RNS) surrogates on March 17, 2016. This report summarizes the results of the work and also includes additional documentation required under test plan PLAN-TA9-2443 Rev B, "Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing Standard Procedure", released February 16, 2016. All formulation and testing was carried out according to PLAN-TA9-2443 Rev B. Results from the first round of formulation and testing were documented in memorandum M7-16-6042, "Results from First Round of Remediated Nitrate Salt Surrogate Formulation and Testing."

  17. Assessing the potential of surrogate EPS to mimic natural biofilm mechanical properties

    Science.gov (United States)

    Thom, Moritz; Schimmels, Stefan

    2017-04-01

    Biofilms growing on benthic sediments may increase the resistance towards erosion considerably by the sticky nature of extracellular polymeric substances (EPS). The EPS is a biopolymer which is secreted by the microorganisms inhabiting the biofilm matrix and may be regarded as natural glue. However, laboratory studies on the biostabilization effect mediated by biofilms are often hampered by the unavailability of "environmental" flumes in which light intensities, water temperature and nutrient content can be controlled. To allow investigations on biostabilization in "traditional" flume settings the use of surrogate materials is studied. Another advantage of using appropriate surrogates is the potential to reduce the experimental time, as compared to cultivating natural biofilms, the surrogates can readily be designed to mimic biofilms at different growth stages. Furthermore, the use of surrogates which are expected to have more homogeneous mechanical properties could facilitate fundamental studies to improve our knowledge on biostabilization. Even though a number of studies have already utilized EPS surrogates it is not clear how to mix them to correctly mimic natural EPS mechanical properties. In this study the adhesiveness (a measure of stickiness) on the surface of several EPS surrogates (e.g. Xanthan Gum, sodium alginate) is measured. These surrogates which are originally used in the food industry as rheology modifiers are mixed by adding water to a powder at a desired concentration (C). The measured surface adhesion of different surrogates at different concentrations ranged from 0.5 to 6.7 N/m2, which is well in line with values found for laboratory cultured biofilms. We found that the surrogate characteristics differed largely especially in regard to a) the response of the adhesiveness to increased concentrations (powder to water) and b) in their rheological characteristics. A seemingly promising surrogate for the use in biostabilization studies is Xanthan Gum

  18. Children of surrogate mothers: psychological well-being, family relationships and experiences of surrogacy.

    Science.gov (United States)

    Jadva, V; Imrie, S

    2014-01-01

    What impact does surrogacy have on the surrogates' own children? The children of surrogate mothers do not experience any negative consequences as a result of their mother's decision to be a surrogate, irrespective of whether or not the surrogate uses her own egg. Participants were recruited as part of a study of the long-term effects of surrogacy for surrogates and their family members. Data were collected from 36 children of surrogates at a single time point. Participants whose mother had been a surrogate 5-15 years prior to interview and who were aged over 12 years were eligible to take part. Thirty-six participants (14 male and 22 female) aged 12-25 years were interviewed (response rate = 52%). Questionnaires assessing psychological health and family functioning were administered. Forty-four per cent (15) of participants' mothers had undergone gestational surrogacy, 39% (14) had used their own egg (genetic surrogacy) and 19% (7) had completed both types of surrogacy. Most surrogates' children (86%, 31) had a positive view of their mother's surrogacy. Forty-seven per cent (17) of children were in contact with the surrogacy child and all reported good relationships with him/her. Forty per cent (14) of children referred to the child as a sibling or half-sibling and this did not differ between genetic and gestational surrogacy. Most children (89%, 32), reported a positive view of family life, with all enjoying spending time with their mother. Mean scores on the questionnaire assessments of psychological health and self-esteem were within the normal range and did not differ by surrogacy type. The sample size for this study was relatively small and not all children chose to take part, therefore their views cannot be known. Nevertheless, this is the first study to assess the experiences of surrogacy from the perspective of the surrogates' own children. There may be some bias from the inclusion of siblings from the same family. Findings of this study show that family

  19. Efficient Calibration of Computationally Intensive Groundwater Models through Surrogate Modelling with Lower Levels of Fidelity

    Science.gov (United States)

    Razavi, S.; Anderson, D.; Martin, P.; MacMillan, G.; Tolson, B.; Gabriel, C.; Zhang, B.

    2012-12-01

    Many sophisticated groundwater models tend to be computationally intensive as they rigorously represent detailed scientific knowledge about the groundwater systems. Calibration (model inversion), which is a vital step of groundwater model development, can require hundreds or thousands of model evaluations (runs) for different sets of parameters and as such demand prohibitively large computational time and resources. One common strategy to circumvent this computational burden is surrogate modelling which is concerned with developing and utilizing fast-to-run surrogates of the original computationally intensive models (also called fine models). Surrogates can be either based on statistical and data-driven models such as kriging and neural networks or simplified physically-based models with lower fidelity to the original system (also called coarse models). Fidelity in this context refers to the degree of the realism of a simulation model. This research initially investigates different strategies for developing lower-fidelity surrogates of a fine groundwater model and their combinations. These strategies include coarsening the fine model, relaxing the numerical convergence criteria, and simplifying the model geological conceptualisation. Trade-offs between model efficiency and fidelity (accuracy) are of special interest. A methodological framework is developed for coordinating the original fine model with its lower-fidelity surrogates with the objective of efficiently calibrating the parameters of the original model. This framework is capable of mapping the original model parameters to the corresponding surrogate model parameters and also mapping the surrogate model response for the given parameters to the original model response. This framework is general in that it can be used with different optimization and/or uncertainty analysis techniques available for groundwater model calibration and parameter/predictive uncertainty assessment. A real-world computationally

  20. Effectiveness of amphibians as biodiversity surrogates in pond conservation.

    Science.gov (United States)

    Ilg, Christiane; Oertli, Beat

    2017-04-01

    Amphibian decline has led to worldwide conservation efforts, including the identification and designation of sites for their protection. These sites could also play an important role in the conservation of other freshwater taxa. In 89 ponds in Switzerland, we assessed the effectiveness of amphibians as a surrogate for 4 taxonomic groups that occur in the same freshwater ecosystems as amphibians: dragonflies, aquatic beetles, aquatic gastropods, and aquatic plants. The ponds were all of high value for amphibian conservation. Cross-taxon correlations were tested for species richness and conservation value, and Mantel tests were used to investigate community congruence. Species richness, conservation value, and community composition of amphibians were weakly congruent with these measures for the other taxonomic groups. Paired comparisons for the 5 groups considered showed that for each metric, amphibians had the lowest degree of congruence. Our results imply that site designation for amphibian conservation will not necessarily provide protection for freshwater biodiversity as a whole. To provide adequate protection for freshwater species, we recommend other taxonomic groups be considered in addition to amphibians in the prioritization and site designation process. © 2016 Society for Conservation Biology.

  1. Numerical investigation for erratic behavior of Kriging surrogate model

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hyun Gil; Yi, Seul Gi [KAIST, Daejeon (Korea, Republic of); Choi, Seong Im [Virginia Polytechnic Institute and State University, Blacksburg (United States)

    2014-09-15

    Kriging model is one of popular spatial/temporal interpolation models in engineering field since it could reduce the time resources for the expensive analysis. But generation of the Kriging model is hardly a sinecure because internal semi-variogram structure of the Kriging often reveals numerically unstable or erratic behaviors. In present study, the issues in the maximum likelihood estimation which are the vital-parts of the construction of the Kriging model, is investigated. These issues are divided into two aspects; Issue I is for the erratic response of likelihood function itself, and Issue II is for numerically unstable behaviors in the correlation matrix. For both issues, studies for specific circumstances which might raise the issue, and the reason of that are conducted. Some practical ways further are suggested to cope with them. Furthermore, the issue is studied for practical problem; aerodynamic performance coefficients of two-dimensional airfoil predicted by CFD analysis. Result shows that such erratic behavior of Kriging surrogate model can be effectively resolved by proposed solution. In conclusion, it is expected this paper could be helpful to prevent such an erratic and unstable behavior.

  2. Protected Gold Nanoparticles with Thioethers and Amines As Surrogate Ligands

    Directory of Open Access Journals (Sweden)

    M. Rafiq H. Siddiqui

    2013-01-01

    Full Text Available Dodecyl sulfide, dodecyl amine, and hexylamine were shown to act as surrogate ligands (L via metastable gold nanoparticles. By collating analytical and spectroscopic data obtained simultaneously, empirical formula Au24L was assigned. These impurity-free nanoparticles obtained in near quantitative yields showing exceptional gold assays (up to 98%Au were prepared by a modification of the two-phase method. Replacement reactions on the Au24L showed that Au:L ratios may be increased (up to Au55:L (L= (H25C122S or decreased (Au12:L (L= H2NC12H25 and H2NC6H13 as desired. This work encompassing the role of analytical techniques used, that is, elemental analysis, variable temperature 1H NMR, FAB mass spectrometry, UV-Vis spectroscopy, thin film X-ray diffraction, and high-resolution electron microscopy (HREM has implications in the study of size control, purity, stability, and metal assays of gold nanoparticles.

  3. Investigation of ethosomes as surrogate carriers for bioactives

    Directory of Open Access Journals (Sweden)

    Devina Verma

    2016-01-01

    Full Text Available Background: Ethosomal vesicular system delivering a bioactive phytochemical, chrysin, was developed for transdermal delivery to increase its permeability and penetrability. Materials and Methods: Ethosomal system was optimized by keeping lecithin and ethanol concentration as independent variable while size and size distribution were taken as dependent variables. The optimized formulation was then subjected to various in vitro characterization parameters. Results: Ethosomal vesicle with an optimum size and polydispersity index of 134 ± 35 nm and 0.153, respectively, and entrapment efficiency of 80.05 ± 2.6% was considered as optimized and subjected to characterization. The scanning electron microscopy and transmission electron microscopy showed spherical entities with uniform surface whereas in vitro permeation and retention study showed the sustained mode of drug release and better skin retention as compared to hydroethanolic solution of the drug. The confocal laser scanning microscopy study reiterated high penetrability of vesicles into the skin. Histopathological and Fourier transform infrared spectroscopy analysis revealed its mechanism of penetration. Conclusion : The study thus demonstrated the ability of the ethosomal vesicles as surrogate carriers for delivery of bioactive agents through the skin for better amelioration of skin inflammation and other diseases.

  4. Midwest Surrogate Species and Prairie Reconstruction Funding Final Report, FY 2016

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Final report on funding received from the Natural Resources Program Center to support surrogate species planning and implementation and the Prairie Reconstruction...

  5. Surrogate Models for Online Monitoring and Process Troubleshooting of NBR Emulsion Copolymerization

    Directory of Open Access Journals (Sweden)

    Chandra Mouli R. Madhuranthakam

    2016-03-01

    Full Text Available Chemical processes with complex reaction mechanisms generally lead to dynamic models which, while beneficial for predicting and capturing the detailed process behavior, are not readily amenable for direct use in online applications related to process operation, optimisation, control, and troubleshooting. Surrogate models can help overcome this problem. In this research article, the first part focuses on obtaining surrogate models for emulsion copolymerization of nitrile butadiene rubber (NBR, which is usually produced in a train of continuous stirred tank reactors. The predictions and/or profiles for several performance characteristics such as conversion, number of polymer particles, copolymer composition, and weight-average molecular weight, obtained using surrogate models are compared with those obtained using the detailed mechanistic model. In the second part of this article, optimal flow profiles based on dynamic optimisation using the surrogate models are obtained for the production of NBR emulsions with the objective of minimising the off-specification product generated during grade transitions.

  6. An Efficient Constraint Boundary Sampling Method for Sequential RBDO Using Kriging Surrogate Model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jihoon; Jang, Junyong; Kim, Shinyu; Lee, Tae Hee [Hanyang Univ., Seoul (Korea, Republic of); Cho, Sugil; Kim, Hyung Woo; Hong, Sup [Korea Research Institute of Ships and Ocean Engineering, Busan (Korea, Republic of)

    2016-06-15

    Reliability-based design optimization (RBDO) requires a high computational cost owing to its reliability analysis. A surrogate model is introduced to reduce the computational cost in RBDO. The accuracy of the reliability depends on the accuracy of the surrogate model of constraint boundaries in the surrogated-model-based RBDO. In earlier researches, constraint boundary sampling (CBS) was proposed to approximate accurately the boundaries of constraints by locating sample points on the boundaries of constraints. However, because CBS uses sample points on all constraint boundaries, it creates superfluous sample points. In this paper, efficient constraint boundary sampling (ECBS) is proposed to enhance the efficiency of CBS. ECBS uses the statistical information of a kriging surrogate model to locate sample points on or near the RBDO solution. The efficiency of ECBS is verified by mathematical examples.

  7. Endospore surface properties of commonly used Bacillus anthracis surrogates vary in aqueous solution

    Science.gov (United States)

    The hydrophobic character and electrophoretic mobility of microorganisms are vital aspects of understanding their interactions with the environment. These properties are fundamental in fate-and-transport, physiological, and virulence studies, and thus integral in surrogate select...

  8. Trimethylsilylethynyl ketones as surrogates for ethynyl ketones in the double Michael reaction.

    Science.gov (United States)

    Holeman, Derrick S; Rasne, Ravindra M; Grossman, Robert B

    2002-05-01

    Trimethylsilylethynyl ketones can be desilylated in the presence of a tethered carbon diacid and induced to undergo a double Michael reaction in situ. The trimethylsilylethynyl ketones can serve as surrogates of ethynyl ketones that are difficult to prepare or isolate.

  9. Novel pH-sensitive interpenetrating network hydrogel beads of carboxymethylcellulose-(polyacrylamide-grafted-alginate) for controlled release of ketoprofen: preparation and characterization.

    Science.gov (United States)

    Kulkarni, Raghavendra V; Sa, Biswanath

    2008-10-01

    Novel pH-sensitive carboxymethylcellulose-(polyacrylamide-grafted-sodium alginate) interpenetrating network (IPN) hydrogel beads loaded with ketoprofen were prepared using ionotropic gelation and covalent crosslinking method. Polyacrylamide-grafted-sodium alginate (PAAm-g-SA) copolymer was synthesized by free radical polymerization using ammonium persulfate (APS) as free radical initiator under the nitrogen atmosphere followed by hydrolysis using sodium hydroxide. The grafting, alkaline hydrolysis and crosslinking reactions were confirmed by Fourier transform infrared spectroscopy (FTIR). Beads were characterized by differential scanning calorimetric (DSC) analysis, thermogravimetric analysis (TGA), X-ray diffractometry (XRD) and scanning electron microscopy (SEM). The mechanical properties of the prepared IPNs were investigated. The erosion was observed with the beads containing only ionic crosslinks whereas it was negligible with the beads containing both ionic and covalent crosslinks. The swelling of the beads and drug release was significantly increased when pH of the medium was changed from acidic to alkaline (P<0.05). The swelling and release data were fitted to an empirical equation to determine the transport mechanism. Drug release followed case II transport mechanism in acidic medium whereas anomalous/non-Fickian transport mechanism was observed in alkaline medium.

  10. Effects of flunixin meglumine and ketoprofen on mediator production in ex vivo and in vitro models of inflammation in healthy dairy cows.

    Science.gov (United States)

    Donalisio, C; Barbero, R; Cuniberti, B; Vercelli, C; Casalone, M; Re, G

    2013-04-01

    In this study, ex vivo assays were carried out in dairy cows to evaluate the anti-inflammatory effects of two nonsteroidal anti-inflammatory drugs: ketoprofen (KETO) and flunixin meglumine (FM). Twelve healthy Holstein dairy cattle were randomly allocated to two groups (n=6): group 1 received FM and group 2 received KETO at recommended therapeutic dosages. The anti-inflammatory effects of both drugs were determined by measuring the production of coagulation-induced thromboxane B2 (TXB2 ), lipopolysaccharides (LPS) (10 μg/mL)-induced prostaglandin E2 (PGE2 ), and calcium ionophore (60 μm)-induced leukotrien B4 (LTB4 ). Cytokine production was assessed by measuring tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-8 (CXCL8) concentrations after incubation in the presence of 10 μg/mL LPS. The IC50 of FM and KETO was determined in vitro by determining the concentration of TXB2 and PGE2 in the presence of scalar drug concentrations (10(-9) -10(-3) m). Both FM and KETO inhibited the two COX isoforms in vitro, but showed a preference for COX-1. FM and KETO showed similar anti-inflammatory effects in the cow.

  11. Improved activity of lipase immobilized in microemulsion-based organogels for (R, S-ketoprofen ester resolution: Long-term stability and reusability

    Directory of Open Access Journals (Sweden)

    Wei-Wei Zhang

    2015-09-01

    Full Text Available Microemulsion-based organogels (MBGs were effectively employed for the immobilization of four commonly used lipases. During the asymmetric hydrolysis of ketoprofen vinyl ester at 30 °C for 24 h, lipase from Rhizomucor miehei and Mucor javanicus immobilized in microemulsion-based organogels (RML MBGs and MJL MBGs maintained good enantioselectivities (eep were 86.2% and 99.2%, respectively, and their activities increased 12.8-fold and 7.8-fold, respectively, compared with their free forms. They gave higher yields compared with other lipase MBGs and exhibited better enantioselectivity than commercial immobilized lipases. Immobilization considerably increased the tolerance to organic solvents and high temperature. Both MJL MBGs and RML MBGs showed excellent reusability during 30 cycles of repeated 24 h reactions at 30 °C (over 40 days. The system maintained yields of greater than 50%, while the ees values of RML MBGs and MJL MBGs remained nearly constant at 95% and 88%, respectively.

  12. Allergic and photoallergic contact dermatitis from ketoprofen: evaluation of cross-reactivities by a combination of photopatch testing and computerized conformational analysis.

    Science.gov (United States)

    Foti, C; Bonamonte, D; Conserva, A; Stingeni, L; Lisi, P; Lionetti, N; Rigano, L; Angelini, G

    2008-01-01

    Allergic contact dermatitis (ACD) and photo-ACD are cell-mediated delayed hypersensitivity reactions of the skin caused by a wide range of substances. Topical ketoprofen (KP), a nonsteroidal anti-inflammatory drug (NSAID), can induce ACD and photo-ACD. Patients with ACD and/or photo-ACD to KP frequently show concomitant sensitization to other substances. The aim of this study was to identify the substances most frequently associated with sensitization to KP, and to evaluate, by means of computerized conformational analysis, whether this association could be due to cross-allergy. 15 subjects with ACD and photo-ACD to KP were tested with the SIDAPA (Società Italiana di Dermatologia Allergologica Professionale ed Ambientale) patch test standard series, including fragrance mix and its components (eugenol, isoeugenol, oak moss, geraniol, hydroxycitronellal, amylcinnamaldehyde, cinnamyl alcohol and cinnamaldehyde) and with the SIDAPA photopatch test series. Allergic reactions to cinnamyl alcohol were noted in all patients, whereas some patients also showed positive reactions to fenticlor, octocrylene and benzophenone-10. Computerized conformational analysis demonstrated that the structure of cinnamyl alcohol is similar to that of KP, whereas the structures of benzophenone-10, octocrylene and fenticlor are completely different. These results suggest that in patients with contact allergy to KP, concomitant positive reactions to cinnamyl alcohol are due to cross-sensitization, whereas simultaneous allergic reactions to fenticlor, octocrylene and benzophenone-10 should be regarded as co-sensitizations.

  13. Significance of Including a Surrogate Arousal for Sleep Apnea-Hypopnea Syndrome Diagnosis by Respiratory Polygraphy

    Science.gov (United States)

    Masa, Juan F.; Corral, Jaime; Gomez de Terreros, Javier; Duran-Cantolla, Joaquin; Cabello, Marta; Hernández-Blasco, Luis; Monasterio, Carmen; Alonso, Alberto; Chiner, Eusebi; Aizpuru, Felipe; Zamorano, Jose; Cano, Ricardo; Montserrat, Jose M.; Garcia-Ledesma, Estefania; Pereira, Ricardo; Cancelo, Laura; Martinez, Angeles; Sacristan, Lirios; Salord, Neus; Carrera, Miguel; Sancho-Chust, José N.; Embid, Cristina

    2013-01-01

    Rationale: Respiratory polygraphy is an accepted alternative to polysomnography (PSG) for sleep apnea/hypopnea syndrome (SAHS) diagnosis, although it underestimates the apnea-hypopnea index (AHI) because respiratory polygraphy cannot identify arousals. Objectives: We performed a multicentric, randomized, blinded crossover study to determine the agreement between home respiratory polygraphy (HRP) and PSG, and between simultaneous respiratory polygraphy (respiratory polygraphy with PSG) (SimultRP) and PSG by means of 2 AHI scoring protocols with or without hyperventilation following flow reduction considered as a surrogate arousal. Methods: We included suspected SAHS patients from 8 hospitals. They were assigned to home and hospital protocols at random. We determined the agreement between respiratory polygraphy AHI and PSG AHI scorings using Bland and Altman plots and diagnostic agreement using receiver operating characteristic (ROC) curves. The agreement in therapeutic decisions (continuous positive airway pressure treatment or not) between HRP and PSG scorings was done with likelihood ratios and post-test probability calculations. Results: Of 366 randomized patients, 342 completed the protocol. AHI from HRP scorings (with and without surrogate arousal) had similar agreement with PSG. AHI from SimultRP with surrogate arousal scoring had better agreement with PSG than AHI from SimultRP without surrogate arousal. HRP with surrogate arousal scoring had slightly worse ROC curves than HRP without surrogate arousal, and the opposite was true for SimultRP scorings. HRP with surrogate arousal showed slightly better agreement with PSG in therapeutic decisions than for HRP without surrogate arousal. Conclusion: Incorporating a surrogate arousal measure into HRP did not substantially increase its agreement with PSG when compared with the usual procedure (HRP without surrogate arousal). Citation: Masa JF; Corral J; Gomez de Terreros J; Duran-Cantolla J; Cabello M; Hern

  14. Using multiscale spatial models to assess potential surrogate habitat for an imperiled reptile.

    Directory of Open Access Journals (Sweden)

    Jennifer M Fill

    Full Text Available In evaluating conservation and management options for species, practitioners might consider surrogate habitats at multiple scales when estimating available habitat or modeling species' potential distributions based on suitable habitats, especially when native environments are rare. Species' dependence on surrogates likely increases as optimal habitat is degraded and lost due to anthropogenic landscape change, and thus surrogate habitats may be vital for an imperiled species' survival in highly modified landscapes. We used spatial habitat models to examine a potential surrogate habitat for an imperiled ambush predator (eastern diamondback rattlesnake, Crotalus adamanteus; EDB at two scales. The EDB is an apex predator indigenous to imperiled longleaf pine ecosystems (Pinus palustris of the southeastern United States. Loss of native open-canopy pine savannas and woodlands has been suggested as the principal cause of the species' extensive decline. We examined EDB habitat selection in the Coastal Plain tidewater region to evaluate the role of marsh as a potential surrogate habitat and to further quantify the species' habitat requirements at two scales: home range (HR and within the home range (WHR. We studied EDBs using radiotelemetry and employed an information-theoretic approach and logistic regression to model habitat selection as use vs.We failed to detect a positive association with marsh as a surrogate habitat at the HR scale; rather, EDBs exhibited significantly negative associations with all landscape patches except pine savanna. Within home range selection was characterized by a negative association with forest and a positive association with ground cover, which suggests that EDBs may use surrogate habitats of similar structure, including marsh, within their home ranges. While our HR analysis did not support tidal marsh as a surrogate habitat, marsh may still provide resources for EDBs at smaller scales.

  15. Surrogate end points in women's health research: science, protoscience, and pseudoscience.

    Science.gov (United States)

    Grimes, David A; Schulz, Kenneth F; Raymond, Elizabeth G

    2010-04-01

    A surrogate end point (e.g., a laboratory test or image) serves as a proxy for a clinical end point of importance (e.g., fracture, thrombosis, or death). Adoption and use of surrogate end points lacking validation, especially in cardiovascular medicine, have caused thousands of patients' deaths, a serious violation of the ethical principle of beneficence. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Postharvest Survival of Porcine Sapovirus, a Human Norovirus Surrogate, on Phytopathogen-Infected Leafy Greens.

    Science.gov (United States)

    Esseili, Malak A; Chin, Ashlina; Saif, Linda; Miller, Sally A; Qu, Feng; Lewis Ivey, Melanie L; Wang, Qiuhong

    2015-08-01

    Leafy greens are increasingly being recognized as an important vehicle for human noroviruses (HuNoV), which cause recurring gastroenteritis outbreaks. Leafy greens often become infected by phytopathogens in the field, which may cause symptoms on the edible parts. Whether plant pathogen infections enhance the survival of HuNoV on leafy greens is unknown. Lettuce and spinach plants were infected with a bacterium, Xanthomonas campestris pv. vitians strain 701a, and with Cucumber mosaic virus strain Fny, respectively. The survival rate of porcine sapovirus (SaV), a HuNoV surrogate, on infected and noninfected postharvest leaves was then assessed. In addition, acibenzolar-S-methyl, a commercial chemical elicitor of plant systemic defense, was used to assess whether stimulating the plant host defense affects the postharvest survival of SaV. Leaves harvested from control and treated plants were inoculated with SaV and incubated for 7 days at 4°C. The infectivity (tissue culture infectious dose affecting 50% of the culture [TCID50]/ml) and RNA (genomic equivalent/ml) titers of SaV were assayed using immunohistochemistry staining and SaV-specific TaqMan real-time reverse transcription PCR. Our results showed that cucumber mosaic virus Fny induced mild, nonnecrotic symptoms on spinach leaves and had no effect on SaV survival. In contrast, X. campestris pv. vitians 701a induced small localized necrotic lesions and significantly enhanced SaV survival on lettuce leaves. Treatment with acibenzolar-S-methyl was effective in reducing X. campestris pv. vitians 701a-induced lesions on infected lettuce plants but had no direct effect on SaV survival when used on healthy lettuce plants. These findings indicate that phytopathogen-induced necrotic lesions may enhance the postharvest survival of HuNoV on lettuce leaves. Therefore, preventive measures aiming to maintain healthy plants and minimize preharvest biological damage are expected to improve the safety of leafy greens.

  17. Measurement of Antioxidant Effects on the Auto-oxidation Kinetics of Methyl Oleate – Methyl Laurate Blend as a Surrogate Biodiesel System

    Directory of Open Access Journals (Sweden)

    Tjokorde Walmiki Samadhi

    2017-05-01

    Full Text Available This research investigates the feasibility of methyl oleate-methyl laurate blend as a surrogate biodiesel system which represents jatropha-coconut oil biodiesel, a potentially suitable formulation for tropical climate, to quantify the efficacy of antioxidant additives in terms of their kinetic parameters. This blend was tested by the Rancimat EN14112 standard method. The Rancimat tests results were used to determine the primary oxidation induction period (OIP and first-order rate constants and activation energies. Addition of BHT and EcotiveTM antioxidants reduces the rate constants (k, h-1 between 15 to 90% in the 50-200 ppm dose range, with EcotiveTM producing significantly lower k values. Higher dose reduces the rate constant, while oleate/laurate ratio produces no significant impact. Antioxidants increase the oxidation activation energy (Ea, kJ/mol by 180 to almost 400% relative to the non-antioxidant value of 27.0 kJ/mol. EcotiveTM exhibits lower Ea, implying that its higher efficacy stems from a better steric hindrance as apparent from its higher pre-exponential factors. The ability to quantify oxidation kinetic parameters is indicative of the usefulness of methyl oleate-laurate pure FAME blend as a biodiesel surrogate offering better measurement accuracy due to the absence of pre-existing antioxidants in the test samples. Copyright © 2017 BCREC GROUP. All rights reserved Received: 6th July 2016; Revised: 7th December 2016; Accepted: 30th January 2017 How to Cite: Samadhi, T.W., Hirotsu, T., Goto, S. (2017. Measurement of Antioxidant Effects on the Auto-oxidation Kinetics of Methyl Oleate-Methyl Laurate Blend as a Surrogate Biodiesel System. Bulletin of Chemical Reaction Engineering & Catalysis, 12 (2: 157-166 (doi:10.9767/bcrec.12.2.861.157-166 Permalink/DOI: http://dx.doi.org/10.9767/bcrec.12.2.861.157-166

  18. Survival of norovirus surrogate on various food-contact surfaces.

    Science.gov (United States)

    Kim, An-Na; Park, Shin Young; Bae, San-Cheong; Oh, Mi-Hwa; Ha, Sang-Do

    2014-09-01

    Norovirus (NoV) is an environmental threat to humans, which spreads easily from one infected person to another, causing foodborne and waterborne diseases. Therefore, precautions against NoV infection are important in the preparation of food. The aim of this study was to investigate the survival of murine norovirus (MNV), as a NoV surrogate, on six different food-contact surfaces: ceramic, wood, rubber, glass, stainless steel, and plastic. We inoculated 10(5) PFU of MNV onto the six different surface coupons that were then kept at room temperature for 28 days. On the food-contact surfaces, the greatest reduction in MNV was 2.28 log10 PFU/coupon, observed on stainless steel, while the lowest MNV reduction was 1.29 log10 PFU/coupon, observed on wood. The rank order of MNV reduction, from highest to lowest, was stainless steel, plastic, rubber, glass, ceramic, and wood. The values of d R (time required to reduce the virus by 90%) on survival plots of MNV determined by a modified Weibull model were 277.60 h (R(2) = 0.99) on ceramic, 492.59 h (R(2) = 0.98) on wood, 173.56 h on rubber (R(2) = 0.98), 97.18 h (R(2) = 0.94) on glass, 91.76 h (R(2) = 0.97) on stainless steel, and 137.74 h (R(2) = 0.97) on plastic. The infectivity of MNV on all food-contact surfaces remained after 28 days. These results show that MNV persists in an infective state on various food-contact surfaces for long periods. This study may provide valuable information for the control of NoV on various food-contact surfaces, in order to prevent foodborne disease.

  19. Composite Sampling Approaches for Bacillus anthracis Surrogate Extracted from Soil.

    Directory of Open Access Journals (Sweden)

    Brian France

    Full Text Available Any release of anthrax spores in the U.S. would require action to decontaminate the site and restore its use and operations as rapidly as possible. The remediation activity would require environmental sampling, both initially to determine the extent of contamination (hazard mapping and post-decon to determine that the site is free of contamination (clearance sampling. Whether the spore contamination is within a building or outdoors, collecting and analyzing what could be thousands of samples can become the factor that limits the pace of restoring operations. To address this sampling and analysis bottleneck and decrease the time needed to recover from an anthrax contamination event, this study investigates the use of composite sampling. Pooling or compositing of samples is an established technique to reduce the number of analyses required, and its use for anthrax spore sampling has recently been investigated. However, use of composite sampling in an anthrax spore remediation event will require well-documented and accepted methods. In particular, previous composite sampling studies have focused on sampling from hard surfaces; data on soil sampling are required to extend the procedure to outdoor use. Further, we must consider whether combining liquid samples, thus increasing the volume, lowers the sensitivity of detection and produces false negatives. In this study, methods to composite bacterial spore samples from soil are demonstrated. B. subtilis spore suspensions were used as a surrogate for anthrax spores. Two soils (Arizona Test Dust and sterilized potting soil were contaminated and spore recovery with composites was shown to match individual sample performance. Results show that dilution can be overcome by concentrating bacterial spores using standard filtration methods. This study shows that composite sampling can be a viable method of pooling samples to reduce the number of analysis that must be performed during anthrax spore remediation.

  20. Composite Sampling Approaches for Bacillus anthracis Surrogate Extracted from Soil

    Science.gov (United States)

    France, Brian; Bell, William; Chang, Emily; Scholten, Trudy

    2015-01-01

    Any release of anthrax spores in the U.S. would require action to decontaminate the site and restore its use and operations as rapidly as possible. The remediation activity would require environmental sampling, both initially to determine the extent of contamination (hazard mapping) and post-decon to determine that the site is free of contamination (clearance sampling). Whether the spore contamination is within a building or outdoors, collecting and analyzing what could be thousands of samples can become the factor that limits the pace of restoring operations. To address this sampling and analysis bottleneck and decrease the time needed to recover from an anthrax contamination event, this study investigates the use of composite sampling. Pooling or compositing of samples is an established technique to reduce the number of analyses required, and its use for anthrax spore sampling has recently been investigated. However, use of composite sampling in an anthrax spore remediation event will require well-documented and accepted methods. In particular, previous composite sampling studies have focused on sampling from hard surfaces; data on soil sampling are required to extend the procedure to outdoor use. Further, we must consider whether combining liquid samples, thus increasing the volume, lowers the sensitivity of detection and produces false negatives. In this study, methods to composite bacterial spore samples from soil are demonstrated. B. subtilis spore suspensions were used as a surrogate for anthrax spores. Two soils (Arizona Test Dust and sterilized potting soil) were contaminated and spore recovery with composites was shown to match individual sample performance. Results show that dilution can be overcome by concentrating bacterial spores using standard filtration methods. This study shows that composite sampling can be a viable method of pooling samples to reduce the number of analysis that must be performed during anthrax spore remediation. PMID:26714315

  1. Composite Sampling Approaches for Bacillus anthracis Surrogate Extracted from Soil.

    Science.gov (United States)

    France, Brian; Bell, William; Chang, Emily; Scholten, Trudy

    2015-01-01

    Any release of anthrax spores in the U.S. would require action to decontaminate the site and restore its use and operations as rapidly as possible. The remediation activity would require environmental sampling, both initially to determine the extent of contamination (hazard mapping) and post-decon to determine that the site is free of contamination (clearance sampling). Whether the spore contamination is within a building or outdoors, collecting and analyzing what could be thousands of samples can become the factor that limits the pace of restoring operations. To address this sampling and analysis bottleneck and decrease the time needed to recover from an anthrax contamination event, this study investigates the use of composite sampling. Pooling or compositing of samples is an established technique to reduce the number of analyses required, and its use for anthrax spore sampling has recently been investigated. However, use of composite sampling in an anthrax spore remediation event will require well-documented and accepted methods. In particular, previous composite sampling studies have focused on sampling from hard surfaces; data on soil sampling are required to extend the procedure to outdoor use. Further, we must consider whether combining liquid samples, thus increasing the volume, lowers the sensitivity of detection and produces false negatives. In this study, methods to composite bacterial spore samples from soil are demonstrated. B. subtilis spore suspensions were used as a surrogate for anthrax spores. Two soils (Arizona Test Dust and sterilized potting soil) were contaminated and spore recovery with composites was shown to match individual sample performance. Results show that dilution can be overcome by concentrating bacterial spores using standard filtration methods. This study shows that composite sampling can be a viable method of pooling samples to reduce the number of analysis that must be performed during anthrax spore remediation.

  2. Interactions between Human Norovirus Surrogates and Acanthamoeba spp.

    Science.gov (United States)

    Hsueh, Tun-Yun; Gibson, Kristen E

    2015-06-15

    Human noroviruses (HuNoVs) are the most common cause of food-borne disease outbreaks, as well as virus-related waterborne disease outbreaks in the United States. Here, we hypothesize that common free-living amoebae (FLA)-ubiquitous in the environment, known to interact with pathogens, and frequently isolated from water and fresh produce-could potentially act as reservoirs of HuNoV and facilitate the environmental transmission of HuNoVs. To investigate FLA as reservoirs for HuNoV, the interactions between two Acanthamoeba species, A. castellanii and A. polyphaga, as well as two HuNoV surrogates, murine norovirus type 1 (MNV-1) and feline calicivirus (FCV), were evaluated. The results showed that after 1 h of amoeba-virus incubation at 25°C, 490 and 337 PFU of MNV-1/ml were recovered from A. castellanii and A. polyphaga, respectively, while only few or no FCVs were detected. In addition, prolonged interaction of MNV-1 with amoebae was investigated for a period of 8 days, and MNV-1 was demonstrated to remain stable at around 200 PFU/ml from day 2 to day 8 after virus inoculation in A. castellanii. Moreover, after a complete amoeba life cycle (i.e., encystment and excystment), infectious viruses could still be detected. To determine the location of virus associated with amoebae, immunofluorescence experiments were performed and showed MNV-1 transitioning from the amoeba surface to inside the amoeba over a 24-h period. These results are significant to the understanding of how HuNoVs may interact with other microorganisms in the environment in order to aid in its persistence and survival, as well as potential transmission in water and to vulnerable food products such as fresh produce.

  3. Design, development, and analysis of a surrogate for pulmonary injury prediction.

    Science.gov (United States)

    Danelson, Kerry A; Gayzik, F Scott; Stern, Amber Rath; Hoth, J Jason; Stitzel, Joel D

    2011-10-01

    Current anthropomorphic test devices (ATDs) measure chest acceleration and deflection to assess risk of injury to the thorax. This study presents a lung surrogate prototype designed to expand the injury assessment capabilities of ATDs to include a risk measure for pulmonary contusion (PC). The surrogate augments these existing measures by providing pressure data specific to the lung and its lobes. The prototype was created from a rendering of a 50th percentile male lung inflated to normal inspiration, obtained from clinical CT data. Surrogate size, lobe volume, and airway cross sections were selected to match the morphology of the lung. Elastomeric urethane was molded via rapid prototyping to create a functional prototype. Pressure sensors in each of the five terminal airways independently monitored pressure traces in the lobes during impacts to the surrogate. Software was created to analyze the surrogate impact pressure data, determine the lobe with the greatest pressure rise for a particular impact, and estimate the initial speed of surface deformation. Calibration testing indicates an approximately linear relationship between peak lobe pressure and surface impact speed. No type I or II errors were demonstrated during lobe detection testing. During repeatability testing, the standard deviation was between 2 and 4% of the mean peak pressure. Ongoing research will focus on correlating surrogate data, pressure pulses, or surface deformation, to risk functions for PC.

  4. Adaptive surrogate model based multi-objective transfer trajectory optimization between different libration points

    Science.gov (United States)

    Peng, Haijun; Wang, Wei

    2016-10-01

    An adaptive surrogate model-based multi-objective optimization strategy that combines the benefits of invariant manifolds and low-thrust control toward developing a low-computational-cost transfer trajectory between libration orbits around the L1 and L2 libration points in the Sun-Earth system has been proposed in this paper. A new structure for a multi-objective transfer trajectory optimization model that divides the transfer trajectory into several segments and gives the dominations for invariant manifolds and low-thrust control in different segments has been established. To reduce the computational cost of multi-objective transfer trajectory optimization, a mixed sampling strategy-based adaptive surrogate model has been proposed. Numerical simulations show that the results obtained from the adaptive surrogate-based multi-objective optimization are in agreement with the results obtained using direct multi-objective optimization methods, and the computational workload of the adaptive surrogate-based multi-objective optimization is only approximately 10% of that of direct multi-objective optimization. Furthermore, the generating efficiency of the Pareto points of the adaptive surrogate-based multi-objective optimization is approximately 8 times that of the direct multi-objective optimization. Therefore, the proposed adaptive surrogate-based multi-objective optimization provides obvious advantages over direct multi-objective optimization methods.

  5. Modeling of Heating and Evaporation of FACE I Gasoline Fuel and its Surrogates

    KAUST Repository

    Elwardani, Ahmed Elsaid

    2016-04-05

    The US Department of Energy has formulated different gasoline fuels called \\'\\'Fuels for Advanced Combustion Engines (FACE)\\'\\' to standardize their compositions. FACE I is a low octane number gasoline fuel with research octane number (RON) of approximately 70. The detailed hydrocarbon analysis (DHA) of FACE I shows that it contains 33 components. This large number of components cannot be handled in fuel spray simulation where thousands of droplets are directly injected in combustion chamber. These droplets are to be heated, broken-up, collided and evaporated simultaneously. Heating and evaporation of single droplet FACE I fuel was investigated. The heating and evaporation model accounts for the effects of finite thermal conductivity, finite liquid diffusivity and recirculation inside the droplet, referred to as the effective thermal conductivity/effective diffusivity (ETC/ED) model. The temporal variations of the liquid mass fractions of the droplet components were used to characterize the evaporation process. Components with similar evaporation characteristics were merged together. A representative component was initially chosen based on the highest initial mass fraction. Three 6 components surrogates, Surrogate 1-3, that match evaporation characteristics of FACE I have been formulated without keeping same mass fractions of different hydrocarbon types. Another two surrogates (Surrogate 4 and 5) were considered keeping same hydrocarbon type concentrations. A distillation based surrogate that matches measured distillation profile was proposed. The calculated molar mass, hydrogen-to-carbon (H/C) ratio and RON of Surrogate 4 and distillation based one are close to those of FACE I.

  6. Band-phase-randomized Surrogates to assess nonlinearity in non-stationary time series

    CERN Document Server

    Guarin, Diego; Orozco, Alvaro

    2011-01-01

    Testing for nonlinearity is one of the most important preprocessing steps in nonlinear time series analysis. Typically, this is done by means of the linear surrogate data methods. But it is a known fact that the validity of the results heavily depends on the stationarity of the time series. Since most physiological signals are non-stationary, it is easy to falsely detect nonlinearity using the linear surrogate data methods. In this document, we propose a methodology to extend the procedure for generating constrained surrogate time series in order to assess nonlinearity in non-stationary data. The method is based on the band-phase-randomized surrogates, which consists (contrary to the linear surrogate data methods) in randomizing only a portion of the Fourier phases in the high frequency band. Analysis of simulated time series showed that in comparison to the linear surrogate data method, our method is able to discriminate between linear stationarity, linear non-stationary and nonlinear time series. When apply...

  7. Errors and Uncertainties in Dose Reconstruction for Radiation Effects Research

    Energy Technology Data Exchange (ETDEWEB)

    Strom, Daniel J.

    2008-04-14

    Dose reconstruction for studies of the health effects of ionizing radiation have been carried out for many decades. Major studies have included Japanese bomb survivors, atomic veterans, downwinders of the Nevada Test Site and Hanford, underground uranium miners, and populations of nuclear workers. For such studies to be credible, significant effort must be put into applying the best science to reconstructing unbiased absorbed doses to tissues and organs as a function of time. In many cases, more and more sophisticated dose reconstruction methods have been developed as studies progressed. For the example of the Japanese bomb survivors, the dose surrogate “distance from the hypocenter” was replaced by slant range, and then by TD65 doses, DS86 doses, and more recently DS02 doses. Over the years, it has become increasingly clear that an equal level of effort must be expended on the quantitative assessment of uncertainty in such doses, and to reducing and managing uncertainty. In this context, this paper reviews difficulties in terminology, explores the nature of Berkson and classical uncertainties in dose reconstruction through examples, and proposes a path forward for Joint Coordinating Committee for Radiation Effects Research (JCCRER) Project 2.4 that requires a reasonably small level of effort for DOSES-2008.

  8. Estudo comparativo entre cetorolaco e cetoprofeno no controle da dor pós-operatória de uvulopalatofaringoplastia A comparative study between Ketorolac and Ketoprofen in postoperative pain after uvulopalatopharyngoplasty

    Directory of Open Access Journals (Sweden)

    Lucas Gomes Patrocínio

    2007-06-01

    Full Text Available A dor no pós-operatório imediato apresenta-se como um grave problema, requerendo do médico uma adequada assistência. Na Otorrinolaringologia, merece atenção especial a dor após uvulopalatofaringoplastia (UPFP. OBJETIVO: Comparar a eficácia na analgesia pós-operatória do cetorolaco com o cetoprofeno em UPFP. PACIENTES E MÉTODOS: Estudo prospectivo, randomizado, duplo-cego com 24 pacientes submetidos à UPFP, divididos em 2 grupos, sendo que 14 receberam cetorolaco e 10 cetoprofeno. Avaliação da intensidade da dor através de escala visual analógica e necessidade do uso associado de opióide (tramadol. RESULTADOS: Dos 14 pacientes que receberam cetorolaco, apenas 3 (21% necessitaram uso complementar de opióide, enquanto que 7 (70% do grupo do cetoprofeno o fizeram. Após 12 horas de cirurgia, houve um predomínio de 71% dos pacientes que receberam cetorolaco, com dor leve ou até ausência desta, enquanto 70% dos do cetoprofeno referiram dor moderada ou incômoda. Após 24 horas de cirurgia, 60% dos pacientes que fizeram uso de cetoprofeno referiam dor moderada a incômoda, ao passo que 86% dos do cetorolaco referiram dor leve à ausência. CONCLUSÃO: Conclui-se que o cetorolaco é mais eficaz em relação ao cetoprofeno no tratamento da dor pós-operatória imediata de UPFP, pois houve dor de menor intensidade e menor uso de opióide.Postoperative pain is a serious problem, requiring an appropriate response from the medical doctor. In otolaryngology special attention is needed after uvulopalatopharyngoplasty (UP3. AIM: To compare the efficacy of postoperative analgesia using ketorolac and ketoprofen after UP3. PATIENTS AND METHODS: A prospective, randomized, double-blind study was made of 24 patients that were divided into 2 groups (14 received ketorolac and 10 received ketoprofen. Pain intensity was based on an analog visual scale and the need for opioids (tramadol. RESULTS: Of the 13 patients that received ketorolac, 3 (21

  9. Ethanol Does Not Promote MeIQx-initiated Rat Colon Carcinogenesis Based on Evidence from Analysis of a Colon Cancer Surrogate Marker.

    Science.gov (United States)

    Kushida, Masahiko; Wanibuchi, Hideki; Wei, Min; Kakehashi, Anna; Ozaki, Keisuke; Sukata, Tokuo; Miyata, Kaori; Ogata, Keiko; Uwagawa, Satoshi; Fukushima, Shoji

    2009-03-01

    Epidemiological studies suggest that alcohol consumption increases the risk of developing colorectal cancer. However, the data are confounded by numerous cosegregating variables. To cast further light on the relationships between alcohol intake and colon cancer development, 21-day-old male F344/DuCrj rats were fed 200 ppm 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in their diet for 8 weeks and doses of 0, 0.1, 0.3, 1, 3, 10 and 20% of ethanol in their drinking water ad libitum for 16 weeks thereafter. The rats were sacrificed after 24 weeks of experiment, and aberrant crypt foci (ACF), surrogate lesions for colon cancer, were examined under a light microscope at low magnification. Ethanol was found not to affect the ACF formation at any dose compared with the initiated-controls. Furthermore, ethanol did not alter colon epithelial cell proliferation. These data, obtained by analysis of a colon cancer surrogate marker lesion, indicate that ethanol lacks promotion activity for MeIQx-initiated rat colon carcinogenesis.

  10. Antiviral Effect of Korean Red Ginseng Extract and Ginsenosides on Murine Norovirus and Feline Calicivirus as Surrogates for Human Norovirus

    Science.gov (United States)

    Lee, Min Hwa; Lee, Bog-Hieu; Jung, Ji-Youn; Cheon, Doo-Sung; Kim, Kyung-Tack; Choi, Changsun

    2011-01-01

    Korean red ginseng has been studied various biological activities such as immune, anti-oxidative, anti-microbial, and anticancer activities but antiviral mechanism needs further studies. In this study, we aimed to examine the antiviral effects of Korea red ginseng extract and ginsenosides on norovirus surrogate, including murine norovirus (MNV) and feline calicivirus (FCV). We evaluated the pre-, co-, and post-treatment effects of Korean red ginseng (KRG), ginsenosides Rb1 and Rg1. To measure the antiviral effect and cytotoxicity of KRG extract, and ginsenosides Rb1 and Rg1, we treated Crandell-Reese Feline Kidney for FCV or RAW264.7 cells for MNV with concentrations of 0, 5, 6.7, 10, 20 ug/mL total saponin. There was cytotoxic effect in the highest concentration 20 ug/mL of KRG extract so this concentration was excluded in this study. The FCV titer was significantly reduced to 0.23-0.83 log10 50% tissue culture infectious dose (TCID50)/mL in groups pre-treated with red ginseng extract or ginsenosides. The titer of MNV was significantly reduced to 0.37-1.48 log10 TCID50/mL in groups pre-treated with red ginseng extract or ginsenosides. However, there was no observed antiviral effect in groups co-treated or post-treated with KRG and its constituents. Our data suggest that KRG extract has an antiviral effect against norovirus surrogates. The antiviral mechanisms of KRG and ginsenosides should be addressed in future studies. PMID:23717088

  11. Organ dose conversions from ESR measurements using tooth enamel of atomic bomb survivors.

    Science.gov (United States)

    Takahashi, Fumiaki; Sato, Kaoru

    2012-03-01

    Dose conversions were studied for dosimetry of atomic bomb survivors based upon electron spin resonance (ESR) measurements of tooth enamel. Previously analysed data had clarified that the tooth enamel dose could be much larger than other organ doses from a low-energy photon exposure. The radiation doses to other organs or whole-body doses, however, are assumed to be near the tooth enamel dose for photon energies which are dominant in the leakage spectrum of the Hiroshima atomic bomb assumed in DS02. In addition, the thyroid can be a candidate for a surrogate organ in cases where the tooth enamel dose is not available in organ dosimetry. This paper also suggests the application of new Japanese voxel phantoms to derive tooth enamel doses by numerical analyses.

  12. Coastal aquifer management under parameter uncertainty: Ensemble surrogate modeling based simulation-optimization

    Science.gov (United States)

    Janardhanan, S.; Datta, B.

    2011-12-01

    Surrogate models are widely used to develop computationally efficient simulation-optimization models to solve complex groundwater management problems. Artificial intelligence based models are most often used for this purpose where they are trained using predictor-predictand data obtained from a numerical simulation model. Most often this is implemented with the assumption that the parameters and boundary conditions used in the numerical simulation model are perfectly known. However, in most practical situations these values are uncertain. Under these circumstances the application of such approximation surrogates becomes limited. In our study we develop a surrogate model based coupled simulation optimization methodology for determining optimal pumping strategies for coastal aquifers considering parameter uncertainty. An ensemble surrogate modeling approach is used along with multiple realization optimization. The methodology is used to solve a multi-objective coastal aquifer management problem considering two conflicting objectives. Hydraulic conductivity and the aquifer recharge are considered as uncertain values. Three dimensional coupled flow and transport simulation model FEMWATER is used to simulate the aquifer responses for a number of scenarios corresponding to Latin hypercube samples of pumping and uncertain parameters to generate input-output patterns for training the surrogate models. Non-parametric bootstrap sampling of this original data set is used to generate multiple data sets which belong to different regions in the multi-dimensional decision and parameter space. These data sets are used to train and test multiple surrogate models based on genetic programming. The ensemble of surrogate models is then linked to a multi-objective genetic algorithm to solve the pumping optimization problem. Two conflicting objectives, viz, maximizing total pumping from beneficial wells and minimizing the total pumping from barrier wells for hydraulic control of

  13. Biomedically assisted reproduction and child birth: Surrogate motherhood in comparative European law and Serbia

    Directory of Open Access Journals (Sweden)

    Kovaček-Stanić Gordana

    2013-01-01

    Full Text Available Surrogate motherhood is an arrangement in which a woman agrees to carry and deliver a child for another couple who ordered the pregnancy. This procedure is applied today in Great Britain, Holland (although without legal regulations, Israel, Greece, Ukraine, Armenia, Georgia, the USA and Australia, and it is forbidden in France, Austria, Spain, Germany, Switzerland and Slovenia. There are two types of surrogacy, one when the woman gives birth to a child who is genetically her own ("partial", genetic surrogacy, and the other where the surrogate mother only carries and gives birth to a child, whereby the child is genetically from the couple that wanted the child, or the fertilized egg is from a third woman (donor, or the embryo was donated ("full", "total", gestational surrogacy. In these cases two women take part in conception and birth of the child while in the last case there is a third woman who will raise the child. Biologically observed, the woman whose egg has been fertilized may be called the genetic mother, while the woman who carried the pregnancy and gave birth to the child - the gestational carrier. Taking into consideration that the Preliminary Draft of the Serbian Civil Law anticipates the introduction of surrogate motherhood into domestic law, we believe restrictive solutions should first be taken into consideration. This would mean that only full surrogating should be allowed, namely the egg should be from the woman who wants the child and not the surrogate mother. In domestic conditions, genetic surrogation should not be allowed as it leads to confusion in family relations, and kinships still have an important social and legal significance in our country. The surrogate mother should be a woman who has already given birth, because in that way any possible shocks which might arise after birth when the woman who has to handover the child to the intended couple would be avoided. The next condition would be that persons involved in this

  14. Comparison of morphine, ketoprofen and Arnica montana 6x and 30x per oral transmucosal or subcutaneous route for control of postoperative pain in cats subjected to hysterectomy with bilateral salpingo-oophorectomy

    Directory of Open Access Journals (Sweden)

    Denise de Fátima Rodrigues

    2016-02-01

    Full Text Available ABSTRACT: The postoperative analgesic effect of Arnica montana (Arnica was compared to morphine and ketoprofen in 50 cats following hysterectomy with bilateral salpingo-oophorectomy (HSO. Cats were randomly allocated to five groups (n=10 and were treated 30 minutes before surgery and over 72 hours with 1ml of Arnica 30x per subcutaneous (SC route (GA30SC; Arnica 30x per oral transmucosal route (P.O. (GA30PO; Arnica 6x P.O. (GA6PO; morphine 0.1mg kg-1 SC (GM SID or ketoprofen 2mg kg-1 SC (GK before and 1mg kg-1 after surgery. Sedation and postoperative pain were assessed by means of a dynamic and interactive visual analogue scale (DIVAS and variable count scale (VCS and hyperalgesia using an esthesiometer. Whenever the VAS and VCS scores attained 33% of the maximum value, rescue analgesia was performed with morphine 0.3mg kg-1 per the intramuscular (IM route. Other variables assessed were vomiting, defecation, urination, body weight and wound healing. Vomiting only occurred in animals treated with morphine. The groups did not differ in defecation, urination, body weight or wound healing. Hyperalgesia was detected only on the occasions that the criterion for rescue analgesia was met. One animal in GK and one in GM required rescue analgesia, differing from groups GA30SC, GA30PO and GA6PO, in which 4, 4 and 5 animals, respectively, required rescue analgesia. It can be concluded that ketoprofen and morphine were more efficacious than Arnica and that there was no difference among the various potencies and routes of administration of Arnica for postoperative analgesia in cats undergoing HSO.

  15. Clinical study on Ketoprofen gel and manipulation in treatment of osteoarthritis%酮洛芬凝胶配合手法治疗膝骨关节炎的临床研究

    Institute of Scientific and Technical Information of China (English)

    李永龙; 黄培炯; 洪笃瑞; 庄鹏; 郑炼生; 朱育雄; 黄明镇

    2011-01-01

    Objective To observe the clinical results of ketoprofen gel and manipulation in the treatment of osteoarthritis of the knee. Methods Totally 98 patients with knee osteoarthritis were randomly divided into manipulation and ketoprofen gel group and manipulation with voltaren group therapy , course of 20 days. Observed two groups before and after the treatment patients indexes, therapeutic effect. Results Two groups of patients after treatment were satisfactory efficacy, efficiency of the treatment group display 81. 63% , efficient 87. 76% ; Control group display efficiency 75. 51% , efficient 79. 59%. The comparison has statistical significance in the two group. Conclusions Ketoprofen gel and manipulation in the treatment of osteoarthritis is efficacy, less side effects.%目的 观察酮洛芬凝胶配合手法治疗膝关节骨关节炎的临床疗效.方法 98例膝关节骨关节炎患者随机分为手法加酮洛芬凝胶组和手法加扶他林组进行治疗,疗程20d.观察治疗前后两组患者病情指标变化、临床疗效.结果 两组患者治疗后均获得满意的临床疗效,治疗组显效率为81.63%,有效率为87.76%;对照组显效率为75.51%,有效率为79.59%.2组对比(P<0.05)有统计学意义.结论 酮洛芬凝胶配合手法治疗膝骨关节炎疗效确切,不良反应少.

  16. L-酒石酸正丁酯萃取拆分酮洛芬外消旋体%Separation of ketoprofen enantiomers by extraction with L-n-butyl tartaric ester

    Institute of Scientific and Technical Information of China (English)

    周丹; 刘佳佳

    2012-01-01

    研究了酮洛芬对映体在含疏水性手性选择体L-酒石酸正丁酯的1,2-二氯乙烷和甲醇水两相体系中的萃取分配行为.考察了酒石酸酯的种类、L-酒石酸正丁酯的浓度、有机溶剂的种类及甲醇溶液的浓度对分配系数K和分离因子α的影响.L-酒石酸正丁酯与S-酮洛芬对映体比L-酒石酸正丁酯与R-酮洛芬对映体形成更稳定的非对映体复合物;以0.2mol/L L-酒石酸正丁酯为手性选择体,以1,2-二氯乙烷为有机溶剂,甲醇浓度为10%时,萃取分离效果最好.%Distribution behavior of ketoprofen enantiomers was examined in the methanol aqueous and organic solvent mixture containing I-n-butyl tartaric ester. The kinds of tartaric esters, the concentration of L-n-butyl tartaric ester and the methanol aqueous,the kinds of organic solvent on the distribution behavior were investigated. The results show that L-n-butyl tartaric ester form more stable diastereomeric complexes with 5-enantiomer than that with R-enantiomer. The best en-antioselectivity for ketoprofen enantiomers was in the separation system consisted of 0. 20 mol/L L-n-butyl tartaric ester as chiral selector, 1, 2-dichloroethane as organic solvent and 10% methanol aqueous as solvent for ketoprofen.

  17. Myotonometry as a Surrogate Measure of Muscle Strength

    Science.gov (United States)

    Ang, B. S.; Feeback, D. L.; Leonard, C. T.; Sykes, J.; Kruger, E.; Clarke, M. S. F.

    2007-01-01

    be significantly (p less than 0.01) correlated with contemporaneous myotonometer measurements made on the rectis femoris muscle in a total of 16 healthy subjects (8 males, 8 females). Further-more, this device has been operationally tested during parabolic flight demonstrating its suitability for use in a microgravity environment. Our data indicates that the Myotonometer is a viable surrogate measure of muscle contractile state/tone and of muscle strength/force production. Additional studies are required to assess the suitability of this technique for assessing these measures in de-conditioned subjects such as crew-members.

  18. Is Diaphragm Motion a Good Surrogate for Liver Tumor Motion?

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Juan [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); School of Information Science and Engineering, Shandong University, Jinan, Shandong (China); Cai, Jing [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Wang, Hongjun [School of Information Science and Engineering, Shandong University, Jinan, Shandong (China); Chang, Zheng; Czito, Brian G. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Bashir, Mustafa R. [Department of Radiology, Duke University Medical Center, Durham, North Carolina (United States); Palta, Manisha [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Yin, Fang-Fang, E-mail: fangfang.yin@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2014-11-15

    Purpose: To evaluate the relationship between liver tumor motion and diaphragm motion. Methods and Materials: Fourteen patients with hepatocellular carcinoma (10 of 14) or liver metastases (4 of 14) undergoing radiation therapy were included in this study. All patients underwent single-slice cine–magnetic resonance imaging simulations across the center of the tumor in 3 orthogonal planes. Tumor and diaphragm motion trajectories in the superior–inferior (SI), anterior–posterior (AP), and medial–lateral (ML) directions were obtained using an in-house-developed normalized cross-correlation–based tracking technique. Agreement between the tumor and diaphragm motion was assessed by calculating phase difference percentage, intraclass correlation coefficient, and Bland-Altman analysis (Diff). The distance between the tumor and tracked diaphragm area was analyzed to understand its impact on the correlation between the 2 motions. Results: Of all patients, the mean (±standard deviation) phase difference percentage values were 7.1% ± 1.1%, 4.5% ± 0.5%, and 17.5% ± 4.5% in the SI, AP, and ML directions, respectively. The mean intraclass correlation coefficient values were 0.98 ± 0.02, 0.97 ± 0.02, and 0.08 ± 0.06 in the SI, AP, and ML directions, respectively. The mean Diff values were 2.8 ± 1.4 mm, 2.4 ± 1.1 mm, and 2.2 ± 0.5 mm in the SI, AP, and ML directions, respectively. Tumor and diaphragm motions had high concordance when the distance between the tumor and tracked diaphragm area was small. Conclusions: This study showed that liver tumor motion had good correlation with diaphragm motion in the SI and AP directions, indicating diaphragm motion in the SI and AP directions could potentially be used as a reliable surrogate for liver tumor motion.

  19. A Development of a Human Cranial Bone Surrogate for Impact Studies

    Directory of Open Access Journals (Sweden)

    Jack C Roberts

    2013-10-01

    Full Text Available In order to replicate the fracture behavior of the intact human skull under impact it becomes necessary to develop a material having the mechanical properties of cranial bone. The most important properties to replicate in a surrogate human skull were found to be the fracture toughness and tensile strength of the cranial tables as well as the bending strength of the 3-layer (inner table-diplöe-outer table architecture of the human skull. The materials selected to represent the surrogate cranial tables consisted of two different epoxy resins systems with random milled glass fiber to enhance the strength and stiffness and the materials to represent the surrogate diplöe consisted of three low density foams. Forty-one three-point bending fracture toughness tests were performed on nine material combinations. The materials that best represented the fracture toughness of cranial tables were then selected and formed into tensile samples and tested. These materials were then used with the two surrogate diplöe foam materials to create the three layer surrogate cranial bone samples for three point bending tests. Drop tower tests were performed on flat samples created from these materials and the fracture patterns were very similar to the linear fractures seen in pendulum impacts of intact human skulls. The surrogate cranial tables had the quasi-static fracture toughness and tensile strength of 2.5 MPa√m and 53 ± 4.9 MPa, respectively, while the same properties of human compact bone were 3.1 ± 1.8 MPa√m and 68 ± 18 MPa, respectively. The cranial surrogate had a quasi-static bending strength of 68 ± 5.7 MPa, while that of cranial bone was 82 ± 26 MPa. This material/design is currently being used to construct spherical shell samples for drop tower and ballistic tests.

  20. Observing Migration and Burial of Unexploded Ordnance in the Nearshore Environment with Instrumented Surrogates

    Science.gov (United States)

    Bruder, B. L.; Cristaudo, D.; Puleo, J. A.

    2016-12-01

    Prior to 1972, it was legal and common practice to unload unexploded ordnance (UXO) into the ocean. Only 60-100 miles off the US coast alone there are 72 dumping sites where it is estimated 31 million pounds of UXO lie. As recently as 2015, UXO have been found not only in the nearshore environment, but on populated beaches. Thus, understanding the migration and burial of these objects is not only of oceanographic interest, but a matter of public safety. The presented project evaluates the efficacy of instrumented UXO surrogates for observing munition migration and burial. Instrumented surrogates were exposed to near prototype scale wave conditions over a mobile bed at the Littoral Warfare Environment at Aberdeen Test Center, MD. Surrogates were deployed in the swash zone, inner and outer surf zones. Dependent on munition size, surrogates housed multiple suites of self-logging sensors. Sensor suites included different combinations of inertial motion units, ultra-wideband tracking tags, pressure transducers, shock recorders, and photocells. Preliminary results show sensor suites can resolve various types of surrogate movement. Pressure transducers accurately record ambient wave conditions as well as changes in mean depth due to surrogate migration. Inertial motion units resolve munition accelerations for rolling and translational motion. Inertial motion unit data is used to estimate trajectory as well when coupled with mean depth and bathymetric data. Photocells, which measure ambient light, resolve munition burial as well as serve as proxies for surrounding environmental conditions such as suspended sediment and water depth. The presented project will continue to utilize and couple surrogate sensor data to resolve munition movement and burial under different conditions. Knowledge of munition migration helps focus UXO detection and recovery, conserving US military and coastal resources.

  1. Primary Reference Fuels (PRFs) as Surrogates for Low Sensitivity Gasoline Fuels

    KAUST Repository

    Bhavani Shankar, Vijai Shankar

    2016-04-05

    Primary Reference Fuels (PRFs) - binary mixtures of n-heptane and iso-octane based on Research Octane Number (RON) - are popular gasoline surrogates for modeling combustion in spark ignition engines. The use of these two component surrogates to represent real gasoline fuels for simulations of HCCI/PCCI engines needs further consideration, as the mode of combustion is very different in these engines (i.e. the combustion process is mainly controlled by the reactivity of the fuel). This study presents an experimental evaluation of PRF surrogates for four real gasoline fuels termed FACE (Fuels for Advanced Combustion Engines) A, C, I, and J in a motored CFR (Cooperative Fuels Research) engine. This approach enables the surrogate mixtures to be evaluated purely from a chemical kinetic perspective. The gasoline fuels considered in this study have very low sensitivities, S (RON-MON), and also exhibit two-stage ignition behavior. The first stage heat release, which is termed Low Temperature Heat Release (LTHR), controls the combustion phasing in this operating mode. As a result, the performance of the PRF surrogates was evaluated by its ability to mimic the low temperature chemical reactivity of the real gasoline fuels. This was achieved by comparing the LTHR from the engine pressure histories. The PRF surrogates were able to consistently reproduce the amount of LTHR, closely match the phasing of LTHR, and the compression ratio for the start of hot ignition of the real gasoline fuels. This suggests that the octane quality of a surrogate fuel is a good indicator of the fuel’s reactivity across low (LTC), negative temperature coefficient (NTC), and high temperature chemical (HTC) reactivity regimes.

  2. Ovulation Statuses of Surrogate Gilts Are Associated with the Efficiency of Excellent Pig Cloning.

    Directory of Open Access Journals (Sweden)

    Yanjun Huan

    Full Text Available Somatic cell nuclear transfer (SCNT is an assisted reproductive technique that can produce multiple copies of excellent livestock. However, low cloning efficiency limits the application of SCNT. In this study, we systematically investigated the major influencing factors related to the overall cloning efficiency in pigs. Here, 13620 cloned embryos derived from excellent pigs were transferred into 79 surrogate gilts, and 119 live cloned piglets were eventually generated. During cloning, group of cloned embryos derived from excellent Landrace or Large white pigs presented no significant differences of cleavage and blastocyst rates, blastocyst cell numbers, surrogate pregnancy and delivery rates, average numbers of piglets born and alive and cloning efficiencies, and group of 101-150, 151-200 or 201-250 cloned embryos transferred per surrogate also displayed a similar developmental efficiency. When estrus stage of surrogate gilts was compared, group of embryo transfer on Day 2 of estrus showed significantly higher pregnancy rate, delivery rate, average number of piglets born, average alive piglet number or cloning efficiency than group on Day 1, Day 3, Day 4 or Day 5, respectively (P<0.05. And, in comparison with the preovulation and postovulation groups, group of surrogate gilts during periovulation displayed a significantly higher overall cloning efficiency (P<0.05. Further investigation of surrogate estrus stage and ovulation status displayed that ovulation status was the real factor underlying estrus stage to determine the overall cloning efficiency. And more, follicle puncture for preovulation, not transfer position shallowed for preovulation or deepened for postovulation, significantly improved the average number of piglets alive and cloning efficiency (P<0.05. In conclusion, our results demonstrated that ovulation status of surrogate gilts was the fundamental factor determining the overall cloning efficiency of excellent pigs, and follicle

  3. Real-time characterization of partially observed epidemics using surrogate models.

    Energy Technology Data Exchange (ETDEWEB)

    Safta, Cosmin; Ray, Jaideep; Lefantzi, Sophia; Crary, David (Applied Research Associates, Arlington, VA); Sargsyan, Khachik; Cheng, Karen (Applied Research Associates, Arlington, VA)

    2011-09-01

    We present a statistical method, predicated on the use of surrogate models, for the 'real-time' characterization of partially observed epidemics. Observations consist of counts of symptomatic patients, diagnosed with the disease, that may be available in the early epoch of an ongoing outbreak. Characterization, in this context, refers to estimation of epidemiological parameters that can be used to provide short-term forecasts of the ongoing epidemic, as well as to provide gross information on the dynamics of the etiologic agent in the affected population e.g., the time-dependent infection rate. The characterization problem is formulated as a Bayesian inverse problem, and epidemiological parameters are estimated as distributions using a Markov chain Monte Carlo (MCMC) method, thus quantifying the uncertainty in the estimates. In some cases, the inverse problem can be computationally expensive, primarily due to the epidemic simulator used inside the inversion algorithm. We present a method, based on replacing the epidemiological model with computationally inexpensive surrogates, that can reduce the computational time to minutes, without a significant loss of accuracy. The surrogates are created by projecting the output of an epidemiological model on a set of polynomial chaos bases; thereafter, computations involving the surrogate model reduce to evaluations of a polynomial. We find that the epidemic characterizations obtained with the surrogate models is very close to that obtained with the original model. We also find that the number of projections required to construct a surrogate model is O(10)-O(10{sup 2}) less than the number of samples required by the MCMC to construct a stationary posterior distribution; thus, depending upon the epidemiological models in question, it may be possible to omit the offline creation and caching of surrogate models, prior to their use in an inverse problem. The technique is demonstrated on synthetic data as well as

  4. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    DEFF Research Database (Denmark)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

    2007-01-01

    to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders. METHODS: After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate...... endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation...... of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery...

  5. Determination on ketoprofen in plasma by HPLC%高效液相色谱法测定血浆中酮洛芬的浓度

    Institute of Scientific and Technical Information of China (English)

    吴万征

    2001-01-01

    目的:建立血浆中酮洛芬的HPLC测定法。方法:色谱柱为SpherisorbC18柱,流动相为5mmol·L-1磷酸盐缓冲液(pH6.8)-甲醇(28∶72),流速1ml·min-1,内标物为萘普生,在UV262nm波长处检测。结果:在此分析条件下酮洛芬和内标分离完全且无其他干扰,保留时间分别为12.3和9.5min。在0.01~5.0μg·ml-1浓度范围内酮洛芬峰面积比与其浓度间呈良好的线性关系,r=0.9990,血浆中酮洛芬最低检测浓度为3μg·ml-1,回收率85.9%~90.9%,日内、日间RSD分别为1.4%~4.9%和2.5%~6.2%。结论:本法简便、灵敏,可用于临床血药浓度监测。%OBJECTIVE To establish an HPLC determination method forketoprofen in plasma. METHODS Column: Spherisorb C18 (100 mm×4.6 mm, 3 μm), Mobile phase:5 mmol·L-1 of phosphate buffer(pH 6.8)-methanol(28∶72, v/v), with flow rate of 1 ml·min-1, and detection wavelength of 262 nm. The sensitivity was 0.005 auf, and the internal standard naproxen. 1 ml of plasma sample was taken for the preparation of testing sample.RESULTS Ketoprofen was completely separated from the internal standard, and no interference was found. The retention time was 12.3 and 9.5 min, respectively. The peak areas of ketoprofen within the concentration range between 0.01~5.0 μg·ml-1 showed good linearity to the concentrations, r=0.9990. The detection limit of keteprofen in plasma was 3 μg·ml-1. The recovery was 85.9%~90.9%, the variation within one day was 1.4%~4.9%, and that between days was 2.5%~6.2%. CONCLUSIONS This method is simple, sensitive.

  6. Skin Safety Studies on Ketoprofen Ethosomal Gels%酮洛芬醇质体凝胶的皮肤安全性实验

    Institute of Scientific and Technical Information of China (English)

    罗丽萍; 韩瑞玲; 王军; 何文

    2013-01-01

    Objective:To study the toxicology of ketoprofen ethosomal (KPFE) gels to evaluate the bio-safety.Method:Guineapigs as the test animals,the toxicity in the complete and damaged skin treated by KPFE gels in a short time was observed,and the local irritation in the complete and damaged skin treated by KPFE gels with single or multiple dosage was studied.The general toxicity was also investigated after treated by KPFE gels for many times.Result:None of the tests showed the significant toxicity,local irritation or general toxicity.Conclusion:KPFE gels with promising skin application safety is valuable to be studied further.%目的:对酮洛芬醇质体(KPFE)凝胶的毒理进行研究,以评价其生物安全性.方法:以豚鼠为实验动物,分别观察其完整皮肤及破损皮肤短时间接触KPFE凝胶后所产生的毒性反应,完整皮肤及破损皮肤单次与多次接触KPFE凝胶后的局部刺激反应,并观察皮肤多次接触KPFE凝胶后机体免疫系统在皮肤上的反应.结果:KPFE凝胶在豚鼠完整或破损皮肤局部均无明显刺激性及毒性反应,多次使用后,未见明显的其他毒性反应.结论:KPFE凝胶具有较高的皮肤应用安全性,值得进一步研究.

  7. The influence of dissolved H2O content in supercritical carbon dioxide to the inclusion complexes formation of ketoprofen/β-cyclodextrin

    Science.gov (United States)

    Goenawan, Joshua; Trisanti, P. N.; Sumarno

    2015-12-01

    This work studies the relation between dissolved H2O content in supercritical carbon dioxide (SC-CO2) with the formation of ketoprofen (KP)/β-cyclodextrin(CD) inclusion complexes. The process involves a physical mixture of these two compounds into contact with the supercritical carbon dioxide which had been previously saturated with H2O over a certain duration. The pressure used for saturation process is 130 bar and saturation temperature was ranged between 30 °C to 50 °C. The inclusion process was achieved by keeping it for 2 hours at 160 bar and 200 bar with inclusion temperature of 50 °C. The results enable us to suggest explanations for the inclusion formation. The inclusion complexes can be formed by contacting the dissolved H2O in SC-CO2 to the physical mixture of KP and CD. An increase in the temperature of saturation process resulted in an increase of dissolved H2O content in the supercritical carbon dioxide. The increasing levels of this water soluble resulted an increase in the inclusion complexes that has been formed. The formation of inclusion complexes includes the water molecules enhancing the emptying of the CD cavities and being replaced by KP, towards a more stable energy state. The drug release used for analyzing the dissolution rate of the KP/CD complexes. The results vary from 79,85% to 99,98% after 45 minutes which is above the rate that has been assigned by Farmakope Indonesia at 70% dissolution rate for KP. The use of SC-CO2 offers a new methods for increasing the rate of dissolution of drugs that are hydrophobic such as KP. CO2 used as a supercritical fluid because of its relatively low cost, easily obtainable supercritical conditions, and lack of toxicity. The material samples were characterized by DSC and Spectrophotometer UV-vis technique.

  8. In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

    Science.gov (United States)

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L

    2012-10-01

    The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard.

  9. Development of a multi-objective optimization algorithm using surrogate models for coastal aquifer management

    Science.gov (United States)

    Kourakos, George; Mantoglou, Aristotelis

    2013-02-01

    SummaryThe demand for fresh water in coastal areas and islands can be very high due to increased local needs and tourism. A multi-objective optimization methodology is developed, involving minimization of economic and environmental costs while satisfying water demand. The methodology considers desalinization of pumped water and injection of treated water into the aquifer. Variable density aquifer models are computationally intractable when integrated in optimization algorithms. In order to alleviate this problem, a multi-objective optimization algorithm is developed combining surrogate models based on Modular Neural Networks [MOSA(MNNs)]. The surrogate models are trained adaptively during optimization based on a genetic algorithm. In the crossover step, each pair of parents generates a pool of offspring which are evaluated using the fast surrogate model. Then, the most promising offspring are evaluated using the exact numerical model. This procedure eliminates errors in Pareto solution due to imprecise predictions of the surrogate model. The method has important advancements compared to previous methods such as precise evaluation of the Pareto set and alleviation of propagation of errors due to surrogate model approximations. The method is applied to an aquifer in the Greek island of Santorini. The results show that the new MOSA(MNN) algorithm offers significant reduction in computational time compared to previous methods (in the case study it requires only 5% of the time required by other methods). Further, the Pareto solution is better than the solution obtained by alternative algorithms.

  10. Combining endangered plants and animals as surrogates to identify priority conservation areas in Yunnan, China

    Science.gov (United States)

    Yang, Feiling; Hu, Jinming; Wu, Ruidong

    2016-08-01

    Suitable surrogates are critical for identifying optimal priority conservation areas (PCAs) to protect regional biodiversity. This study explored the efficiency of using endangered plants and animals as surrogates for identifying PCAs at the county level in Yunnan, southwest China. We ran the Dobson algorithm under three surrogate scenarios at 75% and 100% conservation levels and identified four types of PCAs. Assessment of the protection efficiencies of the four types of PCAs showed that endangered plants had higher surrogacy values than endangered animals but that the two were not substitutable; coupled endangered plants and animals as surrogates yielded a higher surrogacy value than endangered plants or animals as surrogates; the plant-animal priority areas (PAPAs) was the optimal among the four types of PCAs for conserving both endangered plants and animals in Yunnan. PAPAs could well represent overall species diversity distribution patterns and overlap with critical biogeographical regions in Yunnan. Fourteen priority units in PAPAs should be urgently considered as optimizing Yunnan’s protected area system. The spatial pattern of PAPAs at the 100% conservation level could be conceptualized into three connected conservation belts, providing a valuable reference for optimizing the layout of the in situ protected area system in Yunnan.

  11. Combining endangered plants and animals as surrogates to identify priority conservation areas in Yunnan, China.

    Science.gov (United States)

    Yang, Feiling; Hu, Jinming; Wu, Ruidong

    2016-08-19

    Suitable surrogates are critical for identifying optimal priority conservation areas (PCAs) to protect regional biodiversity. This study explored the efficiency of using endangered plants and animals as surrogates for identifying PCAs at the county level in Yunnan, southwest China. We ran the Dobson algorithm under three surrogate scenarios at 75% and 100% conservation levels and identified four types of PCAs. Assessment of the protection efficiencies of the four types of PCAs showed that endangered plants had higher surrogacy values than endangered animals but that the two were not substitutable; coupled endangered plants and animals as surrogates yielded a higher surrogacy value than endangered plants or animals as surrogates; the plant-animal priority areas (PAPAs) was the optimal among the four types of PCAs for conserving both endangered plants and animals in Yunnan. PAPAs could well represent overall species diversity distribution patterns and overlap with critical biogeographical regions in Yunnan. Fourteen priority units in PAPAs should be urgently considered as optimizing Yunnan's protected area system. The spatial pattern of PAPAs at the 100% conservation level could be conceptualized into three connected conservation belts, providing a valuable reference for optimizing the layout of the in situ protected area system in Yunnan.

  12. Surrogate utility estimation by long-term partners and unfamiliar dyads

    Directory of Open Access Journals (Sweden)

    Richard J Tunney

    2015-03-01

    Full Text Available To what extent are people able to make predictions about other people’s preferences and values? We report two experiments that present a novel method assessing some of the basic processes in surrogate decision-making, namely surrogate-utility estimation. In each experiment participants formed dyads who were asked to assign utilities to health related items and commodity items, and to predict their partner’s utility judgments for the same items. In experiment one we showed that older adults in long-term relationships were able to accurately predict their partner’s wishes. In experiment two we showed that younger adults who were relatively unfamiliar with one another were also able to predict other people’s wishes. Crucially we demonstrated that these judgments were accurate even after partialling out each participant’s own preferences indicating that in order to make surrogate utility estimations people engage in perspective-taking rather than simple anchoring and adjustment, suggesting that utility estimation is not the cause of inaccuracy in surrogate decision-making. The data and implications are discussed with respect to theories of surrogate decision-making.

  13. Surrogate POD models for building forming limit diagrams of parameterized sheet metal forming applications

    Science.gov (United States)

    Hamdaoui, M.; Le Quilliec, Guénhaël; Breitkopf, Piotr; Villon, Pierre

    2013-05-01

    The aim of this work is to present a surrogate POD (Proper Orthogonal Decomposition) approach for building forming limit diagrams at minimum cost for parameterized sheet metal formed work-pieces. First, a Latin Hypercube Sampling is performed on the design parameter space. Then, at each design site, displacement fields are computed using the popular open-source finite element software Code_Aster. Then, the method of snapshots is used for POD mode determination. POD coefficients are interpolated using kriging. Furthermore, an error analysis of the surrogate POD model is performed on a validation set. It is shown that on the considered use case the accuracy of the surrogate POD model is excellent for the representation of finite element displacement fields. The validated surrogate POD model is then used to build forming limit diagrams (FLD) for any design parameter to assess the quality of stamped metal sheets. Using the surrogate POD model, the Green-Lagrange strain tensor is derived, then major and minor principal deformations are determined at Gauss points for each mesh element. Furthermore, a signed distance between the forming limit curve in rupture and the obtained cloud of points in the plane (ɛ2, ɛ1) is computed to assess the quality of the formed workpiece. The minimization of this signed distance allows determining the safest design for the chosen use case.

  14. Stochastic structural optimization using particle swarm optimization, surrogate models and Bayesian statistics

    Institute of Scientific and Technical Information of China (English)

    Jongbin Im; Jungsun Park

    2013-01-01

    This paper focuses on a method to solve structural optimization problems using particle swarm optimization (PSO),surrogate models and Bayesian statistics.PSO is a random/stochastic search algorithm designed to find the global optimum.However,PSO needs many evaluations compared to gradient-based optimization.This means PSO increases the analysis costs of structural optimization.One of the methods to reduce computing costs in stochastic optimization is to use approximation techniques.In this work,surrogate models are used,including the response surface method (RSM) and Kriging.When surrogate models are used,there are some errors between exact values and approximated values.These errors decrease the reliability of the optimum values and discard the realistic approximation of using surrogate models.In this paper,Bayesian statistics is used to obtain more reliable results.To verify and confirm the efficiency of the proposed method using surrogate models and Bayesian statistics for stochastic structural optimization,two numerical examples are optimized,and the optimization of a hub sleeve is demonstrated as a practical problem.

  15. Time-varying surrogate data to assess nonlinearity in nonstationary time series: application to heart rate variability.

    Science.gov (United States)

    Faes, Luca; Zhao, He; Chon, Ki H; Nollo, Giandomenico

    2009-03-01

    We propose a method to extend to time-varying (TV) systems the procedure for generating typical surrogate time series, in order to test the presence of nonlinear dynamics in potentially nonstationary signals. The method is based on fitting a TV autoregressive (AR) model to the original series and then regressing the model coefficients with random replacements of the model residuals to generate TV AR surrogate series. The proposed surrogate series were used in combination with a TV sample entropy (SE) discriminating statistic to assess nonlinearity in both simulated and experimental time series, in comparison with traditional time-invariant (TIV) surrogates combined with the TIV SE discriminating statistic. Analysis of simulated time series showed that using TIV surrogates, linear nonstationary time series may be erroneously regarded as nonlinear and weak TV nonlinearities may remain unrevealed, while the use of TV AR surrogates markedly increases the probability of a correct interpretation. Application to short (500 beats) heart rate variability (HRV) time series recorded at rest (R), after head-up tilt (T), and during paced breathing (PB) showed: 1) modifications of the SE statistic that were well interpretable with the known cardiovascular physiology; 2) significant contribution of nonlinear dynamics to HRV in all conditions, with significant increase during PB at 0.2 Hz respiration rate; and 3) a disagreement between TV AR surrogates and TIV surrogates in about a quarter of the series, suggesting that nonstationarity may affect HRV recordings and bias the outcome of the traditional surrogate-based nonlinearity test.

  16. Weanling piglet cerebellum: a surrogate for tolerance to MRT (microbeam radiation therapy) in pediatric neuro-oncology

    Science.gov (United States)

    Laissue, Jean A.; Blattmann, Hans; Di Michiel, Marco; Slatkin, Daniel N.; Lyubimova, Nadia; Guzman, Raphael; Zimmermann, Werner; Birrer, Stephan; Bley, Tim; Kircher, Patrick; Stettler, Regina; Fatzer, Rosmarie; Jaggy, Andre; Smilowitz, Henry; Brauer, Elke; Bravin, Alberto; Le Duc, Geraldine; Nemoz, Christian; Renier, Michel; Thomlinson, William C.; Stepanek, Jiri; Wagner, Hans-Peter

    2001-12-01

    The cerebellum of the weanling piglet (Yorkshire) was used as a surrogate for the radiosensitive human infant cerebellum in a Swiss-led program of experimental microbeam radiation therapy (MRT) at the ESRF. Five weanlings in a 47 day old litter of seven, and eight weanlings in a 40 day old litter of eleven were irradiated in November, 1999 and June, 2000, respectively. A 1.5 cm-wide x 1.5 xm-high array of equally space approximately equals 20-30 micrometers wide, upright microbeams spaced at 210 micrometers intervals was propagated horizontally, left to right, through the cerebella of the prone, anesthetized piglets. Skin-entrance intra-microbeam peak adsorbed doses were uniform, either 150, 300, 425, or 600 gray (Gy). Peak and inter-microbeam (valley) absorbed doses in the cerebellum were computed with the PSI version of the Monte Carlo code GEANT and benchmarked using Gafchromic and radiochromic film microdosimetry. For approximately equals 66 weeks [first litter; until euthanasia], or approximately equals 57 weeks [second litter; until July 30, 2001] after irradiation, the littermates were developmentally, behaviorally, neurologically and radiologically normal as observed and tested by experienced farmers and veterinary scientists unaware of which piglets were irradiated or sham-irradiated. Morever, MRT implemented at the ESRF with a similar array of microbeams and a uniform skin-entrance peak dose of 625 Gy, followed by immunoprophylaxis, was shown to be palliative or curative in young adult rats bearing intracerebral gliosarcomas. These observations give further credence to MRT's potential as an adjunct therapy for brain tumors in infancy, when seamless therapeutic irradiation of the brain is hazardous.

  17. Neutron-induced cross sections of actinides via the surrogate-reaction method

    Directory of Open Access Journals (Sweden)

    Ducasse Q.

    2013-12-01

    Full Text Available The surrogate-reaction method is an indirect way of determining cross sections for reactions that proceed through a compound nucleus. This technique may enable neutron-induced cross sections to be extracted for short-lived nuclei that otherwise cannot be measured. However, the validity of the surrogate method has to be investigated. In particular, the absence of a compound nucleus formation and the Jπ dependence of the decay probabilities may question the method. In this work we study the reactions 238U(d,p239U, 238U(3He,t238Np, 238U(3He,4He237U as surrogates for neutron-induced reactions on 238U, 237Np and 236U, respectively, for which good quality data exist. The experimental set-up enabled the measurement of fission and gamma-decay probabilities. The first results are hereby presented.

  18. Surrogate fuel formulation for light naphtha combustion in advanced combustion engines

    KAUST Repository

    Ahmed, Ahfaz

    2015-03-30

    Crude oil once recovered is further separated in to several distinct fractions to produce a range of energy and chemical products. One of the less processed fractions is light naphtha (LN), hence they are more economical to produce than their gasoline and diesel counterparts. Recent efforts have demonstrated usage of LN as transportation fuel for internal combustion engines with slight modifications. In this study, a multicomponent surrogate fuel has been developed for light naphtha fuel using a multi-variable nonlinear constrained optimization scheme. The surrogate, consisting of palette species n-pentane, 2-methylhexane, 2-methylbutane, n-heptane and toluene, was validated against the LN using ignition quality tester following ASTM D6890 methodology. Comparison of LN and the surrogate fuel demonstrated satisfactory agreement.

  19. Enhanced CRISPR/Cas9-mediated biallelic genome targeting with dual surrogate reporter-integrated donors.

    Science.gov (United States)

    Wu, Yun; Xu, Kun; Ren, Chonghua; Li, Xinyi; Lv, Huijiao; Han, Furong; Wei, Zehui; Wang, Xin; Zhang, Zhiying

    2017-03-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has recently emerged as a simple, yet powerful genome engineering tool, which has been widely used for genome modification in various organisms and cell types. However, screening biallelic genome-modified cells is often time-consuming and technically challenging. In this study, we incorporated two different surrogate reporter cassettes into paired donor plasmids, which were used as both the surrogate reporters and the knock-in donors. By applying our dual surrogate reporter-integrated donor system, we demonstrate high frequency of CRISPR/Cas9-mediated biallelic genome integration in both human HEK293T and porcine PK15 cells (34.09% and 18.18%, respectively). Our work provides a powerful genetic tool for assisting the selection and enrichment of cells with targeted biallelic genome modification. © 2017 Federation of European Biochemical Societies.

  20. Two-step nuclear reactions: The Surrogate Method, the Trojan Horse Method and their common foundations

    Energy Technology Data Exchange (ETDEWEB)

    Hussein, Mahir S. [DCTA, Instituto Tecnologico de Aeronautica, Sao Jose dos Campos, SP (Brazil); Universidade de Sao Paulo, Instituto de Estudos Avancados, C. P. 72012, Sao Paulo, SP (Brazil); Universidade de Sao Paulo, Instituto de Fisica, C. P. 66318, Sao Paulo, SP (Brazil)

    2017-05-15

    In this Letter I argue that the Surrogate Method, used to extract the fast neutron capture cross section on actinide target nuclei, which has important practical application for the next generation of breeder reactors, and the Trojan Horse Method employed to extract reactions of importance to nuclear astrophysics, have a common foundation, the Inclusive Non-Elastic Breakup (INEB) Theory. Whereas the Surrogate Method relies on the premise that the extracted neutron cross section in a (d, p) reaction is predominantly a compound-nucleus one, the Trojan Horse Method assumes a predominantly direct process for the secondary reaction induced by the surrogate fragment. In general, both methods contain both direct and compound contributions, and I show how these seemingly distinct methods are in fact the same but at different energies and different kinematic regions. The unifying theory is the rather well developed INEB theory. (orig.)

  1. Validating (d,pγ as a Surrogate for Neutron Capture

    Directory of Open Access Journals (Sweden)

    Ratkiewicz A.

    2015-01-01

    Full Text Available The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the r-process may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,pγ reaction at low energies was identified as a promising surrogate for the (n,γ reaction, as both reactions share many characteristics. We report on a program to validate (d,pγ as a surrogate for (n,γ using 95Mo as a target. The experimental campaign includes direct measurements of the γ-ray intensities from the decay of excited states populated in the 95Mo(n,γ and 95Mo(d,pγ reactions.

  2. Analytical approximations for temperature dependent thermophysical properties of supercritical diesel fuel surrogates used in combustion modeling

    Science.gov (United States)

    Kumar, Abhinav; Saini, Vishnu; Dondapati, Raja Sekhar; Usurumarti, Preeti Rao

    2017-07-01

    Supercritical fluid technology is introduced to combat the critical challenges related with emissions, incomplete and clean diesel fuel combustion. The chemical kinetics of diesel fuel is a strong function of temperature. As surrogate fuels have a potential to represent a real diesel fuel, thermophysical properties of such fuels have been studied in this present work as a function of temperature. Further, two diesel surrogate fuels which have been identified as the components of actual diesel fuel for jet engines are studied and thermophysical properties of these two surrogates are evaluated as a function of temperature at critical pressure. In addition, the accuracy and reliability of the developed correlations is estimated using two statistical parameters such as Absolute Average of Relative Error (AARE) and Sum of Average Residues (SAR). Results show an excellent agreement between the standard data and the correlated property values.

  3. Validating (d,pγ) as a surrogate for neutron capture

    Energy Technology Data Exchange (ETDEWEB)

    Ratkiewicz, A. [Rutgers Univ., New Brunswick, NJ (United States); Cizewski, J. A. [Rutgers Univ., New Brunswick, NJ (United States); Pain, S. D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Adekola, A. S. [Rutgers Univ., New Brunswick, NJ (United States); Burke, J. T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Casperson, R. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Fotiadis, Nikolaos [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); McCleskey, M. [Texas A & M Univ., College Station, TX (United States); Burcher, S. [Rutgers Univ., New Brunswick, NJ (United States); Shand, C. M [Rutgers Univ., New Brunswick, NJ (United States); Austin, R. A. E. [Saint Mary' s Univ., Halifax (Canada); Baugher, T. [Rutgers Univ., New Brunswick, NJ (United States); Carpenter, M. P. [Argonne National Lab. (ANL), Argonne, IL (United States); Devlin, Matthew James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Escher, J. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hardy, S. [Rutgers Univ., New Brunswick, NJ (United States); Hatarik, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Howard, M. E. [Rutgers Univ., New Brunswick, NJ (United States); Hughes, R. O. [Univ. of Richmond, VA (United States); Jones, K. L. [Univ. of Tennessee, Knoxville, TN (United States); Kozub, R. L. [Tennessee Technological Univ., Cookeville, TN (United States); Lister, C. J. [Univ. of Massachusetts, Lowell, MA (United States); Manning, B. [Rutgers Univ., New Brunswick, NJ (United States); O' Donnell, John M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Peters, W. A. [oak ridge associated Univ., TN (United States); Ross, T. J. [Univ. of Richmond, VA (United States); Scielzo, N. D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Seweryniak, D. [Argonne National Lab. (ANL), Argonne, IL (United States); Zhu, S. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-02-13

    The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the r-process may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,pγ) reaction at low energies was identified as a promising surrogate for the (n,γ) reaction, as both reactions share many characteristics. We report on a program to validate (d,pγ) as a surrogate for (n,γ) using 95Mo as a target. The experimental campaign includes direct measurements of the γ-ray intensities from the decay of excited states populated in the 95Mo(n,γ) and 95Mo(d,pγ) reactions.

  4. Kinetic Modeling of Gasoline Surrogate Components and Mixtures under Engine Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Mehl, M; Pitz, W J; Westbrook, C K; Curran, H J

    2010-01-11

    Real fuels are complex mixtures of thousands of hydrocarbon compounds including linear and branched paraffins, naphthenes, olefins and aromatics. It is generally agreed that their behavior can be effectively reproduced by simpler fuel surrogates containing a limited number of components. In this work, an improved version of the kinetic model by the authors is used to analyze the combustion behavior of several components relevant to gasoline surrogate formulation. Particular attention is devoted to linear and branched saturated hydrocarbons (PRF mixtures), olefins (1-hexene) and aromatics (toluene). Model predictions for pure components, binary mixtures and multicomponent gasoline surrogates are compared with recent experimental information collected in rapid compression machine, shock tube and jet stirred reactors covering a wide range of conditions pertinent to internal combustion engines (3-50 atm, 650-1200K, stoichiometric fuel/air mixtures). Simulation results are discussed focusing attention on the mixing effects of the fuel components.

  5. Two-step nuclear reactions: The Surrogate Method, the Trojan Horse Method and their common foundations

    Science.gov (United States)

    Hussein, Mahir S.

    2017-05-01

    In this Letter I argue that the Surrogate Method, used to extract the fast neutron capture cross section on actinide target nuclei, which has important practical application for the next generation of breeder reactors, and the Trojan Horse Method employed to extract reactions of importance to nuclear astrophysics, have a common foundation, the Inclusive Non-Elastic Breakup (INEB) Theory. Whereas the Surrogate Method relies on the premise that the extracted neutron cross section in a ( d, p) reaction is predominantly a compound-nucleus one, the Trojan Horse Method assumes a predominantly direct process for the secondary reaction induced by the surrogate fragment. In general, both methods contain both direct and compound contributions, and I show how these seemingly distinct methods are in fact the same but at different energies and different kinematic regions. The unifying theory is the rather well developed INEB theory.

  6. Neutron-induced cross sections of actinides via the surrogate-reaction method

    Directory of Open Access Journals (Sweden)

    Tveten G. M.

    2013-03-01

    Full Text Available The surrogate-reaction method is an indirect way of determining cross sections for reactions that proceed through a compound nucleus. This technique may enable neutron-induced cross sections to be extracted for short-lived nuclei that otherwise cannot be measured. However, the validity of the surrogate method for extracting capture cross sections has to be investigated. In this work we study the reactions 238U(d,p239U, 238U(3He,t238Np, 238U(3He,4He237U as surrogates for neutroninduced reactions on 238U, 237Np and 236U, respectively, for which good quality data exist. The experimental set-up enabled the measurement of fission and gamma-decay probabilities. First results are presented and discussed.

  7. Validating (d,p gamma) as a Surrogate for Neutron Capture

    Energy Technology Data Exchange (ETDEWEB)

    Ratkiewicz, A. [Rutgers University; Cizewski, J. A. [Rutgers University; Pain, S. [Oak Ridge National Laboratory (ORNL); Adekola, A. S. [Rutgers University; Burke, J. T. [Lawrence Livermore National Laboratory (LLNL); Casperson, R.J. [Lawrence Livermore National Laboratory (LLNL); Fotiades, N. [Los Alamos National Laboratory (LANL); McCleskey, M. [Texas A& M University; Burcher, S. [Rutgers University; Shand, C. M. [Rutgers Univ./Univ. of Surrey, UK; Austin, R. A. E. [Saint Mary’s University, Halifa, Canada; Baugher, T. [Rutgers University; Carpenter, M. P. [Argonne National Laboratory (ANL); Devlin, M. [Los Alamos National Laboratory (LANL); Escher, J. E. [Lawrence Livermore National Laboratory (LLNL); Hardy, S. [Rutgers Univ./Univ. of Surrey, UK; Hatarik, R. [Lawrence Livermore National Laboratory (LLNL); Howard, M. [Rutgers University; Hughes, R. [University of Richmond, VA; Jones, K. L. [University of Tennessee, Knoxville (UTK); Kozub, R. L. [Tennessee Technological University (TTU); Lister, C. J. [University of Massachusetts, Lowell; Manning, B. [Rutgers University; O' Donnell, J. M. [Los Alamos National Laboratory (LANL); Peters, W. A. [Oak Ridge Associated Universities (ORAU); Ross, T.J. [University of Richmond, VA; Scielzo, N.D. [Lawrence Livermore National Laboratory (LLNL); Seweryniak, D. [Argonne National Laboratory (ANL); Zhu, S. [Argonne National Laboratory (ANL)

    2015-01-01

    The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the rprocess may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,py) reaction at low energies was identified as a promising surrogate for the (n,y) reaction, as both reactions share many characteristics. We report on a program to validate (d,py) as a surrogate for (n,y) using 95Mo as a target. The experimental campaign includes direct measurements of the y-ray intensities from the decay of excited states populated in the 95Mo(n,y) and 95Mo(d,py) reactions.

  8. Adaptive surrogate modeling for response surface approximations with application to bayesian inference

    KAUST Repository

    Prudhomme, Serge

    2015-09-17

    Parameter estimation for complex models using Bayesian inference is usually a very costly process as it requires a large number of solves of the forward problem. We show here how the construction of adaptive surrogate models using a posteriori error estimates for quantities of interest can significantly reduce the computational cost in problems of statistical inference. As surrogate models provide only approximations of the true solutions of the forward problem, it is nevertheless necessary to control these errors in order to construct an accurate reduced model with respect to the observables utilized in the identification of the model parameters. Effectiveness of the proposed approach is demonstrated on a numerical example dealing with the Spalart–Allmaras model for the simulation of turbulent channel flows. In particular, we illustrate how Bayesian model selection using the adapted surrogate model in place of solving the coupled nonlinear equations leads to the same quality of results while requiring fewer nonlinear PDE solves.

  9. Low-dose spinal neostigmine further enhances the analgesic effect of spinal bupivacaine combined with epidural dexamethasone, following orthopedic surgery

    Directory of Open Access Journals (Sweden)

    Gabriela Rocha Lauretti

    2014-01-01

    Full Text Available Background: Opioids are considered mainstream for combined spinal-epidural anesthesia, but frequently limited by adverse effects. The aim of this study was to examine whether low-dose spinal neostigmine, epidural dexamethasone or their combination enhances analgesia from spinal bupivacaine without adverse effects. Materials and Methods : A total of 60 patients undergoing orthopedic surgery were randomized to one of four groups and evaluated for 24-h after surgery for analgesia (time to first rescue analgesic and rescue analgesic consumption. Patients received 15 mg bupivacaine plus the test drug intrathecally (saline or 1 microgram (μg neostigmine. The epidural test drug was either saline or 10 mg dexamethasone. The Control group (CG received spinal and epidural saline. The Neostigmine group (NG, spinal neostigmine and epidural saline; the Dexamethasone group (DG, spinal saline and epidural dexamethasone; and the Neostigmine-dexamethasone group (NDG, spinal neostigmine and epidural dexamethasone. Results: The CG (282 ± 163 min and NG (524 ± 142 min were similar in their times to first rescue analgesic and analgesic consumption. The time to first rescue analgesic was longer for the DG (966 ± 397 min compared with CG and NG (P < 0.0002, and the DG had less ketoprofen consumption and lower overall visual analogue scale-pain sores compared with CG and NG (P < 0.0005. Addition of 1 mg-neostigmine (NDG resulted in longer time to rescue analgesic (1205 ± 303 min; P < 0.02 and lower ketoprofen consumption (P < 0.05 compared to DG. Sporadic cases of vesical catheterization and emesis were observed, however adverse effects were similar among groups. Conclusion: Spinal 1 microgram (μg neostigmine further enhanced analgesia from spinal bupivacaine combined with epidural dexamethasone, without increasing the incidence of adverse effects.

  10. Testing Pairwise Association between Spatially Autocorrelated Variables: A New Approach Using Surrogate Lattice Data

    Science.gov (United States)

    Deblauwe, Vincent; Kennel, Pol; Couteron, Pierre

    2012-01-01

    Background Independence between observations is a standard prerequisite of traditional statistical tests of association. This condition is, however, violated when autocorrelation is present within the data. In the case of variables that are regularly sampled in space (i.e. lattice data or images), such as those provided by remote-sensing or geographical databases, this problem is particularly acute. Because analytic derivation of the null probability distribution of the test statistic (e.g. Pearson's r) is not always possible when autocorrelation is present, we propose instead the use of a Monte Carlo simulation with surrogate data. Methodology/Principal Findings The null hypothesis that two observed mapped variables are the result of independent pattern generating processes is tested here by generating sets of random image data while preserving the autocorrelation function of the original images. Surrogates are generated by matching the dual-tree complex wavelet spectra (and hence the autocorrelation functions) of white noise images with the spectra of the original images. The generated images can then be used to build the probability distribution function of any statistic of association under the null hypothesis. We demonstrate the validity of a statistical test of association based on these surrogates with both actual and synthetic data and compare it with a corrected parametric test and three existing methods that generate surrogates (randomization, random rotations and shifts, and iterative amplitude adjusted Fourier transform). Type I error control was excellent, even with strong and long-range autocorrelation, which is not the case for alternative methods. Conclusions/Significance The wavelet-based surrogates are particularly appropriate in cases where autocorrelation appears at all scales or is direction-dependent (anisotropy). We explore the potential of the method for association tests involving a lattice of binary data and discuss its potential for

  11. Calibration of an agricultural-hydrological model (RZWQM2) using surrogate global optimization

    Science.gov (United States)

    Xi, Maolong; Lu, Dan; Gui, Dongwei; Qi, Zhiming; Zhang, Guannan

    2017-01-01

    Robust calibration of an agricultural-hydrological model is critical for simulating crop yield and water quality and making reasonable agricultural management. However, calibration of the agricultural-hydrological system models is challenging because of model complexity, the existence of strong parameter correlation, and significant computational requirements. Therefore, only a limited number of simulations can be allowed in any attempt to find a near-optimal solution within an affordable time, which greatly restricts the successful application of the model. The goal of this study is to locate the optimal solution of the Root Zone Water Quality Model (RZWQM2) given a limited simulation time, so as to improve the model simulation and help make rational and effective agricultural-hydrological decisions. To this end, we propose a computationally efficient global optimization procedure using sparse-grid based surrogates. We first used advanced sparse grid (SG) interpolation to construct a surrogate system of the actual RZWQM2, and then we calibrate the surrogate model using the global optimization algorithm, Quantum-behaved Particle Swarm Optimization (QPSO). As the surrogate model is a polynomial with fast evaluation, it can be efficiently evaluated with a sufficiently large number of times during the optimization, which facilitates the global search. We calibrate seven model parameters against five years of yield, drain flow, and NO3-N loss data from a subsurface-drained corn-soybean field in Iowa. Results indicate that an accurate surrogate model can be created for the RZWQM2 with a relatively small number of SG points (i.e., RZWQM2 runs). Compared to the conventional QPSO algorithm, our surrogate-based optimization method can achieve a smaller objective function value and better calibration performance using a fewer number of expensive RZWQM2 executions, which greatly improves computational efficiency.

  12. Multimission Fuel-Burn Minimization in Aircraft Design: A Surrogate-Modeling Approach

    Science.gov (United States)

    Liem, Rhea Patricia

    Aerodynamic shape and aerostructural design optimizations that maximize the performance at a single flight condition result in designs with unacceptable off-design performance. While considering multiple flight conditions in the optimization improves the robustness of the designs, there is a need to develop a rational strategy for choosing the flight conditions and their relative emphases such that multipoint optimizations reflect the true objective function. In addition, there is a need to consider uncertain missions and flight conditions. In this thesis, the strategies to formulate the multipoint objective functions for aerodynamic shape and aerostructural optimization are presented. To determine the flight conditions and their corresponding weights, a novel surrogate-based mission analysis is developed to efficiently analyze hundreds of actual mission data to emulate their flight condition distribution. Using accurate and reliable surrogate models to approximate the aerodynamic coefficients used in the analysis makes this procedure computationally tractable. A mixture of experts (ME) approach is developed to overcome the limitations of conventional surrogate models in modeling the complex transonic drag profile. The ME approach combines multiple surrogate models probabilistically based on the divide-andconquer strategy. Using this model in the mission analysis significantly improves the range estimation accuracy, as compared to other conventional surrogate models. As expected, the multipoint aerodynamic shape and aerostructural optimizations demonstrate a consistent drag reduction, instead of the localized improvement by the single-point optimizations. The improved robustness in the multipoint optimized designs was also observed in terms of the improved range performance and more consistent fuel-burn reduction across the different missions. The results presented in this thesis show that the surrogate-model-assisted multipoint optimization produces a robust

  13. Two-dimensional surrogate contact modeling for computationally efficient dynamic simulation of total knee replacements.

    Science.gov (United States)

    Lin, Yi-Chung; Haftka, Raphael T; Queipo, Nestor V; Fregly, Benjamin J

    2009-04-01

    Computational speed is a major limiting factor for performing design sensitivity and optimization studies of total knee replacements. Much of this limitation arises from extensive geometry calculations required by contact analyses. This study presents a novel surrogate contact modeling approach to address this limitation. The approach involves fitting contact forces from a computationally expensive contact model (e.g., a finite element model) as a function of the relative pose between the contacting bodies. Because contact forces are much more sensitive to displacements in some directions than others, standard surrogate sampling and modeling techniques do not work well, necessitating the development of special techniques for contact problems. We present a computational evaluation and practical application of the approach using dynamic wear simulation of a total knee replacement constrained to planar motion in a Stanmore machine. The sample points needed for surrogate model fitting were generated by an elastic foundation (EF) contact model. For the computational evaluation, we performed nine different dynamic wear simulations with both the surrogate contact model and the EF contact model. In all cases, the surrogate contact model accurately reproduced the contact force, motion, and wear volume results from the EF model, with computation time being reduced from 13 min to 13 s. For the practical application, we performed a series of Monte Carlo analyses to determine the sensitivity of predicted wear volume to Stanmore machine setup issues. Wear volume was highly sensitive to small variations in motion and load inputs, especially femoral flexion angle, but not to small variations in component placements. Computational speed was reduced from an estimated 230 h to 4 h per analysis. Surrogate contact modeling can significantly improve the computational speed of dynamic contact and wear simulations of total knee replacements and is appropriate for use in design sensitivity

  14. Testing pairwise association between spatially autocorrelated variables: a new approach using surrogate lattice data.

    Directory of Open Access Journals (Sweden)

    Vincent Deblauwe

    Full Text Available BACKGROUND: Independence between observations is a standard prerequisite of traditional statistical tests of association. This condition is, however, violated when autocorrelation is present within the data. In the case of variables that are regularly sampled in space (i.e. lattice data or images, such as those provided by remote-sensing or geographical databases, this problem is particularly acute. Because analytic derivation of the null probability distribution of the test statistic (e.g. Pearson's r is not always possible when autocorrelation is present, we propose instead the use of a Monte Carlo simulation with surrogate data. METHODOLOGY/PRINCIPAL FINDINGS: The null hypothesis that two observed mapped variables are the result of independent pattern generating processes is tested here by generating sets of random image data while preserving the autocorrelation function of the original images. Surrogates are generated by matching the dual-tree complex wavelet spectra (and hence the autocorrelation functions of white noise images with the spectra of the original images. The generated images can then be used to build the probability distribution function of any statistic of association under the null hypothesis. We demonstrate the validity of a statistical test of association based on these surrogates with both actual and synthetic data and compare it with a corrected parametric test and three existing methods that generate surrogates (randomization, random rotations and shifts, and iterative amplitude adjusted Fourier transform. Type I error control was excellent, even with strong and long-range autocorrelation, which is not the case for alternative methods. CONCLUSIONS/SIGNIFICANCE: The wavelet-based surrogates are particularly appropriate in cases where autocorrelation appears at all scales or is direction-dependent (anisotropy. We explore the potential of the method for association tests involving a lattice of binary data and discuss its

  15. Surrogate analysis and index developer (SAID) tool and real-time data dissemination utilities

    Science.gov (United States)

    Domanski, Marian M.; Straub, Timothy D.; Wood, Molly S.; Landers, Mark N.; Wall, Gary R.; Brady, Steven J.

    2015-01-01

    The use of acoustic and other parameters as surrogates for suspended-sediment concentrations (SSC) in rivers has been successful in multiple applications across the Nation. Critical to advancing the operational use of surrogates are tools to process and evaluate the data along with the subsequent development of regression models from which real-time sediment concentrations can be made available to the public. Recent developments in both areas are having an immediate impact on surrogate research, and on surrogate monitoring sites currently in operation. The Surrogate Analysis and Index Developer (SAID) standalone tool, under development by the U.S. Geological Survey (USGS), assists in the creation of regression models that relate response and explanatory variables by providing visual and quantitative diagnostics to the user. SAID also processes acoustic parameters to be used as explanatory variables for suspended-sediment concentrations. The sediment acoustic method utilizes acoustic parameters from fixed-mount stationary equipment. The background theory and method used by the tool have been described in recent publications, and the tool also serves to support sediment-acoustic-index methods being drafted by the multi-agency Sediment Acoustic Leadership Team (SALT), and other surrogate guidelines like USGS Techniques and Methods 3-C4 for turbidity and SSC. The regression models in SAID can be used in utilities that have been developed to work with the USGS National Water Information System (NWIS) and for the USGS National Real-Time Water Quality (NRTWQ) Web site. The real-time dissemination of predicted SSC and prediction intervals for each time step has substantial potential to improve understanding of sediment-related water-quality and associated engineering and ecological management decisions.

  16. 柱前衍生化 RP-HPLC 拆分酮洛芬对映异构体的研究%Study on the Separation of Ketoprofen Enantiomer by Pre-column Derivation RP-HPLC

    Institute of Scientific and Technical Information of China (English)

    林晓燕; 江洁怡; 胥爱丽; 陈昭; 李素梅

    2016-01-01

    Objective:To establish a method for the separation and determination of ketoprofen enantiomer .Methods:A pre-col-umn derivation RP-HPLC method was used with L-alanine-β-naphthylamine ( L-Ala-β-NA) as the derivation reagent .The RP-HPLC conditions were as follows: a Hypersil ODS-2 column (250 mm ×4.6 mm,5 μm) was applied, the mobile phase was acetonitrile-0.025 mol· L-1 phosphate buffer solution (40∶60, v/v) and the flow rate was 1.0 ml· min-1 , the detection wavelength was set at 245 nm and the column temperature was 25℃.The injection volume was 10μl.Results:Base line separation was achieved for the sep-aration of enantiomer from ketoprofen , and the retention time for S-(+) -ketoprofen and the R-(-) -ketoprofen was 24.2 min and 26.0 min, respectively.Dexketoprofen within the range of 0.025-0.125 mg had a good linear relationship (r=0.998 1) and the aver-age recovery was 90.93%(RSD =4.10%, n=9 ).Conclusion:The method is simple, accurate and reliable, which can be applied in the separation and determination of ketoprofen .%目的:建立酮洛芬对映异构体的拆分方法。方法:采用柱前衍生化RP-HPLC法,以L-丙氨酸-β-萘胺( L-Ala-β-NA)为手性衍生化试剂,色谱柱:Hypersil ODS-2柱(250 mm ×4.6 mm,5μm),流动相:乙腈-0.025 mol· L -1磷酸二氢钾溶液(40∶60,v/v),流速:1.0 ml· min-1,检测波长:245 nm,柱温:25℃,进样量:10μl。结果:酮洛芬对映体衍生物获得较好的基线分离,S-(+)-对映体和 R-(-)-对映体衍生物的色谱峰保留时间分别在24.2 min和26.0 min处。右旋酮洛芬在0.025~0.125 mg质量范围内线性关系良好(r=0.9981),平均回收率为90.93%(RSD=4.10%,n=9)。结论:该方法简便、准确、快速,为酮洛芬的光学异构体的测定提供了参考依据。

  17. The 13C-Glucose Breath Test for Insulin Resistance Assessment in Adolescents: Comparison with Fasting and Post-Glucose Stimulus Surrogate Markers of Insulin Resistance

    Science.gov (United States)

    Maldonado-Hernández, Jorge; Martínez-Basila, Azucena; Salas-Fernández, Alejandra; Navarro-Betancourt, José R.; Piña-Aguero, Mónica I.; Bernabe-García, Mariela

    2016-01-01

    Objective: To evaluate the use of the 13C-glucose breath test (13C-GBT) for insulin resistance (IR) detection in adolescents through comparison with fasting and post-glucose stimulus surrogates. Methods: One hundred thirty-three adolescents aged between 10 and 16 years received an oral glucose load of 1.75 g per kg of body weight dissolved in 150 mL of water followed by an oral dose of 1.5 mg/kg of U-13C-Glucose, without a specific maximum dose. Blood samples were drawn at baseline and 120 minutes, while breath samples were obtained at baseline and at 30, 60, 90, 120, 150, and 180 minutes. The 13C-GBT was compared to homeostasis model assessment (HOMA) IR (≥p95 adjusted by gender and age), fasting plasma insulin (≥p90 adjusted by gender and Tanner stage), results of 2-h oral glucose tolerance test (OGTT), insulin levels (≥65 μU/mL) in order to determine the optimal cut-off point for IR diagnosis. Results: 13C-GBT data, expressed as adjusted cumulative percentage of oxidized dose (A% OD), correlated inversely with fasting and post-load IR surrogates. Sexual development alters A% OD results, therefore individuals were stratified into pubescent and post-pubescent. The optimal cut-off point for the 13C-GBT in pubescent individuals was 16.3% (sensitivity=82.8% & specificity=60.6%) and 13.0% in post-pubescents (sensitivity=87.5% & specificity=63.6%), when compared to fasting plasma insulin. Similar results were observed against HOMA and 2-h OGTT insulin. Conclusion: The 13C-GBT is a practical and non-invasive method to screen for IR in adolescents with reasonable sensitivity and specificity. PMID:27354200

  18. Effectiveness of external respiratory surrogates for in vivo liver motion estimation

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Kai-Hsiang; Ho, Ming-Chih; Yeh, Chi-Chuan; Chen, Yu-Chien; Lian, Feng-Li; Lin, Win-Li; Yen, Jia-Yush; Chen, Yung-Yaw [Department of Electrical Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10041, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan (China); Department of Electrical Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Institute of Biomedical Engineering, National Taiwan University, Taipei 10041, Taiwan (China); Department of Mechanical Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Department of Electrical Engineering and Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan (China)

    2012-08-15

    Purpose: Due to low frame rate of MRI and high radiation damage from fluoroscopy and CT, liver motion estimation using external respiratory surrogate signals seems to be a better approach to track liver motion in real-time for liver tumor treatments in radiotherapy and thermotherapy. This work proposes a liver motion estimation method based on external respiratory surrogate signals. Animal experiments are also conducted to investigate related issues, such as the sensor arrangement, multisensor fusion, and the effective time period. Methods: Liver motion and abdominal motion are both induced by respiration and are proved to be highly correlated. Contrary to the difficult direct measurement of the liver motion, the abdominal motion can be easily accessed. Based on this idea, our study is split into the model-fitting stage and the motion estimation stage. In the first stage, the correlation between the surrogates and the liver motion is studied and established via linear regression method. In the second stage, the liver motion is estimated by the surrogate signals with the correlation model. Animal experiments on cases of single surrogate signal, multisurrogate signals, and long-term surrogate signals are conducted and discussed to verify the practical use of this approach. Results: The results show that the best single sensor location is at the middle of the upper abdomen, while multisurrogate models are generally better than the single ones. The estimation error is reduced from 0.6 mm for the single surrogate models to 0.4 mm for the multisurrogate models. The long-term validity of the estimation models is quite satisfactory within the period of 10 min with the estimation error less than 1.4 mm. Conclusions: External respiratory surrogate signals from the abdomen motion produces good performance for liver motion estimation in real-time. Multisurrogate signals enhance estimation accuracy, and the estimation model can maintain its accuracy for at least 10 min. This

  19. Religion and Spirituality in Surrogate Decision Making for Hospitalized Older Adults.

    Science.gov (United States)

    Geros-Willfond, Kristin N; Ivy, Steven S; Montz, Kianna; Bohan, Sara E; Torke, Alexia M

    2016-06-01

    We conducted semi-structured interviews with 46 surrogate decision makers for hospitalized older adults to characterize the role of spirituality and religion in decision making. Three themes emerged: (1) religion as a guide to decision making, (2) control, and (3) faith, death and dying. For religious surrogates, religion played a central role in end of life decisions. There was variability regarding whether God or humans were perceived to be in control; however, beliefs about control led to varying perspectives on acceptance of comfort-focused treatment. We conclude that clinicians should attend to religious considerations due to their impact on decision making.

  20. A Bayesian Surrogate Model for Rapid Time Series Analysis and Application to Exoplanet Observations

    CERN Document Server

    Ford, Eric B; Veras, Dimitri

    2011-01-01

    We present a Bayesian surrogate model for the analysis of periodic or quasi-periodic time series data. We describe a computationally efficient implementation that enables Bayesian model comparison. We apply this model to simulated and real exoplanet observations. We discuss the results and demonstrate some of the challenges for applying our surrogate model to realistic exoplanet data sets. In particular, we find that analyses of real world data should pay careful attention to the effects of uneven spacing of observations and the choice of prior for the "jitter" parameter.

  1. Surrogate pregnancy in a patient who underwent radical hysterectomy and bilateral transposition of ovaries.

    Science.gov (United States)

    Azem, Foad; Yovel, Israel; Wagman, Israel; Kapostiansky, Rita; Lessing, Joseph B; Amit, Ami

    2003-05-01

    To evaluate IVF-surrogate pregnancy in a patient with ovarian transposition after radical hysterectomy for carcinoma of the cervix. Case report. A maternity hospital in Tel Aviv that is a major tertiary care and referral center. A 29-year-old woman who underwent Wertheim's hysterectomy for carcinoma of the uterine cervix and ovarian transposition before total pelvic irradiation. Standard IVF treatment, transabdominal oocyte retrieval, and transfer to surrogate mother. Outcome of IVF cycle. A twin pregnancy in the first cycle. This is the second reported case of controlled ovarian stimulation and oocyte retrieval performed on a transposed ovary.

  2. Initial Results from the Third Round of Remediated Nitrate Salt Surrogate Formulation and Testing

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Geoffrey Wayne [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Leonard, Philip [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hartline, Ernest Leon [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Tian, Hongzhao [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-04-20

    High explosives science and technology (M-7) is currently working on the third round of formulation and testing of Remediated nitrate salt (RNS) surrogates. This report summarizes the calorimetry results from the 15% sWheat mixtures. All formulation and testing was carried out according to PLAN-TA9-2443 Rev B, "Remediated Nitrate Salt (RNS) surrogate formulation and testing standard procedure", released February 16, 2016. Results from the first and second rounds of formulation and testing were documented in memoranda M7-16-6042 and M7-16-6053.

  3. Using serum urate as a validated surrogate end point for flares in patients with gout

    DEFF Research Database (Denmark)

    Morillon, Melanie B; Stamp, Lisa; Taylor, William;

    2016-01-01

    INTRODUCTION: Gout is the most common inflammatory arthritis in men over 40 years of age. Long-term urate-lowering therapy is considered a key strategy for effective gout management. The primary outcome measure for efficacy in clinical trials of urate-lowering therapy is serum urate levels......, effectively acting as a surrogate for patient-centred outcomes such as frequency of gout attacks or pain. Yet it is not clearly demonstrated that the strength of the relationship between serum urate and clinically relevant outcomes is sufficiently strong for serum urate to be considered an adequate surrogate...

  4. Effect of a Disease-Specific Planning Intervention on Surrogate Understanding of Patient Goals for Future Medical Treatment

    Science.gov (United States)

    Kirchhoff, Karin T.; Hammes, Bernard J.; Kehl, Karen A.; Briggs, Linda A.; Brown, Roger L.

    2010-01-01

    Context Patients with life-limiting illnesses, and their families, struggle with complex treatment decisions as these patients approach the last few years of life. Surrogates often do not clearly understand the patient's goals for future medical treatments. Objectives To determine if a disease-specific planning process can improve surrogate understanding of such patient goals for future, medical treatments. Design, Setting, and Participants A multisite randomized controlled trial conducted between January 1, 2004 and July 31, 2007 in 6 outpatient clinics of large community or university health systems in 3 Wisconsin cities. Subjects were patients with either chronic congestive heart failure or chronic renal disease and their surrogate decision makers. Participants had to be competent, English-speaking adults at least 18 years of age. Intervention Trained health professionals conducted a structured, patient-centered interview intended to promote informed decision making and to result in the completion of a document clarifying the goals of the patient with regard to four disease-specific health outcome situations and to the degree of decision-making latitude granted to the surrogate. Measurements Surrogate understanding of patient goals for care with regard to four expected, disease-specific outcomes situations and of the degree of surrogate latitude in decision making. Results Three hundred thirteen patient-surrogate pairs completed the study. As measured by Kappa (κ) scores and in all four situations and in the degree of latitude, intervention group surrogates demonstrated a significantly higher degree of understanding of patient goals than control group surrogates. Intervention group κ scores ranged from 0.61 to 0.78, while control group κ scores ranged from 0.07 to 0.28. Conclusion Surrogates in the intervention group had a significantly better understanding of patient goals and preferences than surrogates in the control group. This finding is the first step

  5. Doubt and belief in physicians' ability to prognosticate during critical illness: the perspective of surrogate decision makers.

    Science.gov (United States)

    Zier, Lucas S; Burack, Jeffrey H; Micco, Guy; Chipman, Anne K; Frank, James A; Luce, John M; White, Douglas B

    2008-08-01

    Although discussing a prognosis is a duty of physicians caring for critically ill patients, little is known about surrogate decision-makers' beliefs about physicians' ability to prognosticate. We sought to determine: 1) surrogates' beliefs about whether physicians can accurately prognosticate for critically ill patients; and 2) how individuals use prognostic information in their role as surrogate decision-makers. Multicenter study in intensive care units of a public hospital, a tertiary care hospital, and a veterans' hospital. We conducted semistructured interviews with 50 surrogate decision-makers of critically ill patients. We analyzed the interview transcripts using grounded theory methods to inductively develop a framework to describe surrogates' beliefs about physicians' ability to prognosticate. Validation methods included triangulation by multidisciplinary analysis and member checking. Overall, 88% (44 of 50) of surrogates expressed doubt about physicians' ability to prognosticate for critically ill patients. Four distinct themes emerged that explained surrogates' doubts about prognostic accuracy: a belief that God could alter the course of the illness, a belief that predicting the future is inherently uncertain, prior experiences where physicians' prognostications were inaccurate, and experiences with prognostication during the patient's intensive care unit stay. Participants also identified several factors that led to belief in physicians' prognostications, such as receiving similar prognostic estimates from multiple physicians and prior experiences with accurate prognostication. Surrogates' doubts about prognostic accuracy did not prevent them from wanting prognostic information. Instead, most surrogate decision-makers view physicians' prognostications as rough estimates that are valuable in informing decisions, but are not determinative. Surrogates identified the act of prognostic disclosure as a key step in preparing emotionally and practically for the

  6. Copeptin - A potential endocrine surrogate marker of CCK-4-induced panic symptoms?

    Science.gov (United States)

    Demiralay, Cüneyt; Agorastos, Agorastos; Yassouridis, Alexander; Jahn, Holger; Wiedemann, Klaus; Kellner, Michael

    2017-02-01

    Intravenous cholecystokinin-tetrapeptide (CCK-4) administration reliably and dose-dependently provokes panic anxiety in man, accompanied by adrenocorticotropic hormone (ACTH) and cortisol release. Preclinical findings suggest that behavioral and endocrine effects of CCK-4 are mediated via corticotropin-releasing hormone (CRH) release. Anxiogenic stimulation of the central CCK-receptors in man was shown to increase as well vasopressin (AVP), which acts synergistically with CRH as pituitary-adrenocortical axis stimulator during stress. Copeptin (CoP), the C-terminal part of pre-pro-AVP, is released in an equimolar ratio to AVP. It is more stable in the circulation and easier to determine than AVP and it was found to closely mirror the production of AVP. So far, CoP secretion has not been characterized during panic provocation. In 30 healthy male human subjects, we repeatedly measured CoP in plasma during a panic challenge and studied its correlation to Acute Panic Inventory (API) ratings and plasma ACTH and cortisol. CoP levels correlated positively with the increase in API ratings (r=0.41, p=0.03), while ACTH or cortisol did not (r=0.08, p=0.68 and r=0.12, p=0.53, respectively). CoP levels correlated also positively with ACTH (r=0.48, p=0.009) and cortisol (r=0.48, p=0.01) concentrations throughout the CCK-4 challenge. As expected, we found a positive correlation between plasma ACTH and cortisol levels (r=0.57, p=0.001). A vasopressinergic activation during CCK-4 induced panic was demonstrated, which was correlated positively to panic symptoms and pituitary-adrenocortical release. Our findings suggest a role of CoP as a potential surrogate marker of CCK-4 panic symptoms. Further studies are needed to replicate our results and to further clarify the role of CoP as a stress-sensitive hormone in different panic paradigms as well as in panic patients.

  7. Surface plasmon resonance biosensor for detection of feline calicivirus, a surrogate for norovirus.

    Science.gov (United States)

    Yakes, Betsy Jean; Papafragkou, Efstathia; Conrad, Stephen M; Neill, John D; Ridpath, Julia F; Burkhardt, William; Kulka, Michael; Degrasse, Stacey L

    2013-03-15

    The human noroviruses are the most common non-bacterial cause of gastroenteritis and are responsible for as much as 50% of all gastroenteritis outbreaks worldwide. Norovirus (NoV), a single stranded RNA virus, is highly contagious with an infectious dose of less than 100 viral particles. While techniques exist for the identification of NoV, the lack of a reliable cell culture system, NoV genetic variability, and time-consuming sample preparation steps required to isolate the virus (or its genome) prior to molecular based methods has hindered rapid virus detection. To better protect the public from virus-contaminated food and enable better detection in clinical and environmental samples, sensitive and selective methods with simple sample preparation are needed. Surface plasmon resonance (SPR) biosensors represent an emerging detection platform, and this approach has been applied to the rapid detection of foodborne small molecule toxins, protein toxins, and bacteria. This analytical technique, however, has yet to be fully investigated for rapid virus detection, especially for intact viral particles extracted from food matrices. For this study, the culturable, non-human pathogen feline calicivirus (FCV), which has similar morphology and is genetically related to NoV, was chosen as a surrogate virus for designing and evaluating an SPR assay. An antibody-based assay was performed by first immobilizing anti-FCV to an SPR chip surface and then directly measuring virus binding and subsequent secondary antibody binding. The resulting biosensor directly detected intact FCV particles with limits of detection of approximately 10(4)TCID50FCV/mL from purified cell culture lysates. In addition, intact virus detection in FCV-spiked oyster matrix was possible when using a simple extraction procedure and employing a secondary antibody to FCV for quantitation. The results from these preliminary studies show promise for the development of a rapid assay for detecting intact viruses

  8. Acoustic dose and acoustic dose-rate.

    Science.gov (United States)

    Duck, Francis

    2009-10-01

    Acoustic dose is defined as the energy deposited by absorption of an acoustic wave per unit mass of the medium supporting the wave. Expressions for acoustic dose and acoustic dose-rate are given for plane-wave conditions, including temporal and frequency dependencies of energy deposition. The relationship between the acoustic dose-rate and the resulting temperature increase is explored, as is the relationship between acoustic dose-rate and radiation force. Energy transfer from the wave to the medium by means of acoustic cavitation is considered, and an approach is proposed in principle that could allow cavitation to be included within the proposed definitions of acoustic dose and acoustic dose-rate.

  9. TH-C-12A-11: Target Correlation of a 3D Surface Surrogate for Left Breast Irradiation Using the Respiratory-Gated Deep-Inspiration Breath-Hold Technique

    Energy Technology Data Exchange (ETDEWEB)

    Rong, Y; Walston, S [A Quick, Ohio State University, Columbus, OH (United States)

    2014-06-15

    Purpose: To evaluate the use of 3D optical surface imaging as a new surrogate for respiratory motion gated deep-inspiration breath-hold (DIBH) technique for left breast cancer patients. Methods: Patients with left-sided breast cancer after lumpectomy or mastectomy were selected as candidates for DIBH technique for their external beam radiation therapy. Treatment plans were created on both free breathing (FB) and DIBH CTs to determine whether DIBH was beneficial in reducing heart doses. The Real-time Position Management (RPM) system was used to acquire patient's breathing trace during DIBH CT acquisition and treatment delivery. The reference 3D surface models from FB and DIBH CTs were generated and transferred to the “AlignRT” system for patient positioning and real-time treatment monitoring. MV Cine images were acquired for each beam as quality assurance for intra-fractional position verification. The chest wall excursions measured on these images were used to define the actual target position during treatment, and to investigate the accuracy and reproducibility of RPM and AlignRT. Results: Reduction in heart dose can be achieved for left-sided breast patients using DIBH. Results showed that RPM has poor correlation with target position, as determined by the MV Cine imaging. This indicates that RPM may not be an adequate surrogate in defining the breath-hold level when used alone. Alternatively, the AlignRT surface imaging demonstrated a better