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A series of 2-substituted phenyl derivatives of nicotinic acid 4a-l were synthesized and evaluated for their analgesic and anti-inflammatory activities. Compounds including 2-bromophenyl substituent, 4a, c, and d, proved to display distinctive analgesic and anti-inflammatory activities in comparison to mefenamic acid as a reference drug. Compound 4c could be identified as the most biologically active member within this study with an interesting dual anti-inflammatory analgesic profile. Effect of the compounds 4a-l on the serum level of certain inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 was also determined.
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1. The aim was to see whether mefenamic acid and salicylic acid had different inhibition profiles for SULT1A1 (substrate: 4-nitrophenol) and SULT1A3 (dopamine) activities and on (-)-salbutamol and minoxidil sulphation rates in the human adult and mid-gestational foetal livers. 2. The activity (pmolmin(-1) mg(-1) of SULT1A1 was 662 +/- 78 (adult) and 246 +/- 159 (foetus; p = 0.003) and that of SULT1A3 was 24 +/- 4 (adult) and 121 +/- 90 (foetus; p = 0.030). The rate (pmol min(-1) mg(-1)) of (-)-salbutamol sulphation was 109 +/- 27 (adult) and 117 +/- 34 (foetus; p = (0.144) and that of minoxidil sulphation was 202 +/- 38 (adult) and 108 +/- 44 (foetus; p = 0.001). 3. With mefenamic acid as an inhibitor, the IC50 (microM) for SULT1A1 was 0.2 +/- 0.004 (adult) and 0.01 +/- 0.002 (foetus; p = 0.001); for SULT1A3 it was 76 +/- 6 (adult) and 77 +/- 13 (foetus; p = 0.889); for the rate of ( )-salbutamol sulphation it was 0.07 +/- 0.005 (adult) and not determinable (foetus) and for minoxidil sulphation it was 1.6 +/- 0.7 (adult) and 0.15 +/- 0.04 (foetus; p = 0.076). 4. With salicylic acid as an inhibitor, the IC50 (microM) for SULT1A1 was 30 +/- 2 (adult) and 25 +/- 1 (foetus; p = 0.011); for SULT1A3 it was 690 +/- 36 (adult) and 570 +/- 16 (foetus; p = 0.229); for the rate of ( )-salbutamol sulphation it was 93 +/- 11 (adult) and 344 +/- 42 (foetus; p = 0.010); with minoxidil as substrate, the IC50 was not determinable. 5. In summary, SULT1A1, SULT1A3 and the sulphotransferases towards (-)-salbutamol and minoxidil had measurable activities in the mid-gestational human foetal liver. Mefenamic acid was a more potent inhibitor than salicylic acid of both human adult and foetal liver SULT1A1 and SULT1A3 activities. Foetal liver SULT1A1 was more susceptible than adult liver SULT1A1 to inhibition by mefenamic acid and salicylic acid. These results are consistent with the view that sulphotransferases develop early in the human foetal liver and drugs may inhibit their activities.
To assess the efficacy of tranexamic acid or mefenamic acid in the management of the initial "nuisance" bleeding or spotting in the period immediately after placement of the levonorgestrel-releasing intrauterine system.
This study shows a correlation between higher prescribed NSAID doses and tablet/capsule formulation, and highlights the need for careful choice of dose formulation when prescribing medicines for children.
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All practices recorded consultation details, treatments offered, and outcomes for women with regular heavy menstrual loss (menorrhagia) over 1 year.
Both of the daily doses of meloxicam tested were comparable to 500 mg mefenamic acid t.i.d. in relieving dysmenorrhea symptoms, and meloxicam seems to have a better gastrointestinal tolerability profile.
Rings of pulmonary vein from control and heartworm-infected dogs were constricted with norepinephrine (10(-5.5)M) and followed over 65 minutes. Time profiles were established by measuring active tension every 2 minutes for the first 10 minutes, then every 5 minutes for 15 minutes, then every 10 minutes for 40 minutes. Time profiles were done in pulmonary vein rings with and without endothelial cells, and in the presence and absence of N-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase inhibitor), mefenamic acid (cyclooxygenase inhibitor), or methylene blue (guanylate cyclase inhibitor).
The effects of two prostaglandin synthesis blockers, indomethacin and mefenemic acid, on both histamine-induced extravasation of albumin and arteriole dilation were studied using intravital fluorescent microscopy. Sprague-Dawley rats (140-180 g) were anesthetized with pentobarbital (50mg/Kg) and the cremaster muscle was positioned in a Krebs bath (pH = 7.4, PCO2 = 40 mm Hg, PO2 = 35 mm Hg, temp = 34 degrees). Fluorescein isothiocyanate-labeled albumin was injected intravascularly and the fluorescent image of the cremaster microcirculation was produced by illumination from an argon laser (488 nm). Videotape analysis of the experiments showed that increasing concentrations of histamine in the bath produced both a concentration-dependent arteriole dilation and a concentration-dependent leakage of labeled albumin into the interstitium. Adding indomethacin (10 or 100 micrograms/ml) or mefenemic acid (10 micrograms/ml) to the Krebs bath significantly diminished the protein leakage induced by histamine but did not alter the arteriole dilation. These results indicate that prostaglandins may be directly involved in the histamine-induced increase in vascular permeability to macromolecules but not in the arteriole dilation histamine produces.
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The effect of hemodialysis on plasma mefenamic acid levels was studied in four patients on long-term hemodialysis. A 500-mg oral dose of mefenamic acid was administered to the fasting patients two hours before hemodialysis. Arterial and venous blood samples taken before dialysis, at 30-minute intervals during a three-hour dialysis, and immediately before termination of dialysis were assayed by high-performance liquid chromatography. Mefenamic acid half-life on hemodialysis was not reduced substantially compared with that reported for normal patients. The extraction efficiency of the hollow-fiber kidneys averaged 6.4%. The mean drug recovery was 1.03 mg or 0.2% of the administered dose. The extensive plasma protein binding (range: 85-97%) accounted for the poor recovery. The study suggests that adjustment of mefenamic acid dosage is not necessary in patients undergoing hemodialysis and that hemodialysis is of minimal value in the management of mefenamate overdose.
The design, preparation and performance for novel UV-light absorbing (room-temperature) ionic liquid matrices (UV-RTILMs) for matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) were reported. A series of UV-RTILMs was prepared by ultrasonication of equimolar of acid (mefenamic acid) and bases (aniline (ANI), pyridine (Pyr), dimethyl aniline (DMANI) and 2-methyl picoline (2-P)). The UV-RTILMs have not only significant absorbance at the desired wavelength (337 nm of the N2 Laser), but also have available protons that can easily undergo proton transfer reactions to ionize the target molecules. The novel UV-RTILMs have the ability to ionize different and wide classes of compounds such as drugs, carbohydrate, and amino acids. The new UV-RTILMs series have been successfully and selectively applied for biosensing the lysates of pathogenic bacteria in the presence of the cell macromolecules. A new strategy for biosensing pathogens was presented via sensing the pathogens lysate in the cell suspension. The new materials can effectively detect the bacterial toxins without separation or any pretreatment. They offered excellent ionization of labile oligosaccharides with protonated peaks. They could significantly enhance the analyte signals, produce homogeneous spotting, reducing spot-to-spot variation, excellent vacuum stability, higher ion peak intensity, and wide application possibility. The physical parameters such as molar refractivity, molar volume, parachor, surface tension, density and polarizability were calculated and tabulated. The new UV-RTILMs could offer excellent reproducibility and great repeatability and they are promising matrices for wide applications on MALDI-MS.