Sixty-nine patients with a convincing history of menorrhagia completed a 4-cycle double-blind randomized placebo-controlled crossover trial of mefenamic acid taken during menstruation. Only 30 of these patients demonstrated objective menorrhagia with a measured menstrual loss greater than 80 ml during the placebo cycles, but the remainder reported passing clots and/or using 2 pads at a time. Fourteen of these women (20%) had a loss of less than 35 ml while taking placebos. This raises serious questions about the establishment of menorrhagia based on history alone. Overall, there was a mean reduction of 28.1% in menstrual blood loss between placebo and mefenamic acid cycles (P less than .001). The greatest reduction recorded was 80%, and most of the large percentage reductions were seen in patients with high loss during placebo cycles. Significant reductions in blood loss (P less than .001) were seen in patients with ovulatory dysfunctional uterine bleeding and menorrhagia that developed after tubal interruption. There was also an indication based on small sample sizes that mefenamic acid reduced blood loss in women with anovulatory dysfunctional uterine bleeding, fibroids, intrauterine devices, and von Willebrand disease. No reduction was seen during the mefenamic acid cycle in the group with a loss of less than 35 ml during the placebo cycle. There was a significant shortening of duration of bleeding (P less than .003). Fifteen patients (21.7%) experienced no objective reduction in blood loss.
We encountered one confirmed aspirin-relieved asthma patient and investigated the effects of cyclooxygenase and lipoxygenase inhibitors on his condition.
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In human subcutaneous resistance arteries in-vitro, the relaxation produced by the novel furopyridine compound cicletanine (30 microMs) was inhibited by 51% (P less than 0.0001) in the presence of 20 microMs of the cyclo-oxygenase inhibitor indomethacin. Maximal cicletanine-induced relaxation was reduced by both the cyclo-oxygenase inhibitor mefenamic acid and the relatively specific blocker of prostacyclin synthetase, tranylcypromine by 55% (P less than 0.0005) and 43% (P less than 0.01), respectively. The potassium channel blocker, glibenclamide (100 microMs), did not affect the relaxation produced by cicletanine but did inhibit the relaxation produced by the potassium channel blocker cromakalim (P less than 0.0001). Cromakalim-induced relaxation was inhibited in the presence of indomethacin; relaxation induced by cromakalim (30 microMs) was reduced by 22% (P less than 0.02). The relaxation produced by the hypotensive agonists sodium nitroprusside, hydrochlorothiazide, bumetanide and nicardipine was unaffected by incubation with indomethacin. The results suggest that the vascular eicosanoid system, specifically prostacyclin, may be involved in the mechanism of the acute vasodilator action of cicletanine. Although at high doses, cicletanine is a diuretic, in this model it did not act like either a thiazide or a loop diuretic. The acute vasodilator action of the thiazide diuretic, hydrochlorothiazide was a novel finding of this study. Cromakalim showed a reduced response in the presence of indomethacin suggesting an involvement of the eicosanoid system in its mechanism of action.
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Stir bar sorptive extraction with polyurethane (PU) and polydimethylsiloxane (PDMS) polymeric phases followed by high-performance liquid chromatography with diode array detection [SBSE(PU or PDMS)/HPLC-DAD] was studied for the determination of six acidic pharmaceuticals [o-acetylsalicylic acid (ACA), ibuprofen (IBU), diclofenac sodium (DIC), naproxen (NAP), mefenamic acid (MEF) and gemfibrozil (GEM)], selected as non-steroidal acidic anti-inflammatory drugs and lipid regulators model compounds in environmental water matrices. The main parameters affecting the efficiency of the proposed methodology are fully discussed. Assays performed on 25 mL of water samples spiked at the 10 microg L(-1) level under optimized experimental conditions, yielded recoveries ranging from 45.3+/-9.0% (ACA) to 90.6+/-7.2% (IBU) by SBSE(PU) and 9.8+/-1.6% (NAP) to 73.4+/-5.0% (GEM) by SBSE(PDMS), where the former polymeric phase presented a better affinity to extract these target analytes from water matrices at the trace level. The methodology showed also excellent linear dynamic ranges for the six acidic pharmaceuticals studied, with correlation coefficients higher than 0.9976, limits of detection and quantification between 0.40-1.7 microg L(-1) and 1.5-5.8 microg L(-1), respectively, and suitable precision (RSD <15%). Moreover, the developed methodology was applied for the determination of these target analytes in several environmental matrices, including river, sea and wastewater samples, having achieved good performance and moderate matrix effects. In short, the PU foams demonstrated to be an excellent alternative for the enrichment of the more polar metabolites from water matrices by SBSE, overcoming the limitations of the conventional PDMS phase.
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Whenever a dentist is dealing with abscess formation in the oral and maxillofacial region, it is mostly from dental origins. However, sometimes uncommon (co-)factors are present and responsible for major complications. Many general conditions or medications can significantly influence the course of an inflammation. It might spread faster and wider and also be resistant to "correct" therapy. This case report should raise awareness about general conditions supporting inflammation and demonstrate the importance of interdisciplinary treatment in these situations. A 76-year-old patient was referred to the maxillofacial surgery clinic after extraction of two teeth resulted in therapy-resistant painful swelling. Her dentist already had initiated "standard" therapy including Ponstan® (mefenamic acid) and Clamoxyl® (amoxicillin) without success. Initial blood testing came back with severe agranulocytosis. Immediately all potentially myelosuppressing drugs were stopped while myelosupporting drugs were prescribed. Under close interdisciplinary treatment conditions, healing was then uneventful without the necessity of surgical intervention. The challenge in inflammation treatment is to identify patients with uncommonly severe, fast-progressing, or therapy-resistant disease as early as possible. Further examination including blood workup for several medical parameters is indispensable in those patients.
Osmotic fragility of red cells is increased by the use of mefenamic acid. The use of this analgesic induces hemolytic anemia. Study of osmotic fragility of RBCs of control and test was observed following administration of 7.1 mg, 10.5 mg and 14 mg/day mefenamic acid to each lizard. Increased osmotic fragility was observed with increase in the amount of dose on day 6 and day 12.
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The human liver and kidney are important sites of MPA glucuronidation. MPA glucuronidation was inhibited to various extents by different NSAIDs and the four most effective inhibitors were niflumic acid, flufenamic acid, mefenamic acid and diflunisal. These drugs have similar molecular structures consisting of two aromatic rings bearing a carboxylic group.
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Primary dysmenorrhea refers to the occurrence of painful menstrual cramps of uterus and is considered as a gynecological complaint. The common treatment for this problem is medical therapy such as mefenamic acid [non-steroidal anti-inflammatory drugs (NSAIDs)] and oral contraceptive pills, both of which work by reducing myometrial activity. Fennel contains an antispasmodic and anethol agents and may be helpful for management of primary dysmenorrhea.
A double-blind study was carried out in 48 patients with soft-tissue injuries to compare the effectiveness of mefenamic acid and dextropropoxyphene plus paracetamol in relieving acute post-injury pain. Patients received capsules containing either 250 mg mefenamic acid or 32.5 mg dextropropoxyphene hydochloride plus 325 mg paracetamol and were instructed to take up to 6 capsules daily as necessary. By the third post-injury day both preparations had controlled pain adequately and lessened local tenderness in most cases. There was no significant difference in response between the two patient groups. Two patients in each group stopped treatment because of gastro-intestinal intolerance, and a further 4 patients in each group reported troublesome side-effects.
The influence exerted by a number of non-steroid antiphlogistic agents on the fermentative mechanism responsible for the formation and decomposition of kininines in an inflammation focus and on the permeability of vessels in a skin changed under the effect of exogenous bradykininine was studied. Bradykininine, chigamin, sodium salicylate and mephenaminate are shown to inhibit "in vitro" the kininogenic and intensify the kininase activity of the exudate in rats with turpentine-induced pleuritis, while indometacin affects only the activity of kininogenases. Butadion, chingamin and sodium mephenaminate merely reduce the reactivity of the skin with respect to exogenous bradykininine.
We examined the effect of 26 drugs on T4 binding to transthyretin (TTR; prealbumin) and T4-binding globulin (TBG) by determining their ability to inhibit [125I]T4 binding to TTR isolated from normal human plasma and to serum diluted 1:10,000, respectively. The hierarchies for drug inhibition of T4 binding differed greatly for these two proteins. Relative to T4, the drugs were much more potent inhibitors of [125I]T4 binding to TTR than to TBG. Compounds of the anthranilic acid class, such as flufenamic, meclofenamic, and mefenamic acids, interacted particularly strongly with TTR. Flufenamic acid was more potent than T4 itself in inhibiting [125I]T4 binding [175 +/- 17% (+/- SD); cf. T4; n = 3; P less than 0.001], while mefenamic acid, diflunisal, and meclofenamic acid were 20-26% as potent as T4 in their interaction with TTR. The reactivity of diclofenac, fenclofenac, indomethacin, sulindac, and the diuretic ethacrynic acid was 0.8-2.1% relative to that of T4. In contrast, furosemide, the drug most highly reactive with TBG, was only 0.11 +/- 0.03% (n = 7) as potent as T4, followed by meclofenamic acid greater than mefenamic acid greater than fenclofenac greater than flufenamic acid greater than diflunisal greater than milrinone. Aspirin and sodium salicylate were, respectively, 0.05% and 0.20% as active as unlabeled T4 as inhibitors of [125I]T4 binding to TTR, but these compounds had only 3-4 x 10(-6)% of the activity of T4 for TBG binding. Diphenylhydantoin had no detectable effect on T4 binding to TTR and was 2.9 x 10(-4)% as reactive as T4 with TBG. Amiodarone did not interact with either binding site. Drug interactions with TTR may be important when this protein becomes a major circulating T4-binding protein, as in patients with complete or partial TBG deficiency, or when serum T4 is markedly elevated. Such interactions may also be important where TTR is the dominant tissue T4-binding protein, as in the choroid plexus. In addition, the drug competitors described here may be useful as probes to further define the structural basis for specific ligand interactions with different classes of T4-binding sites.
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For many clinicians and parents "teething" remains a convenient diagnosis to explain all manner of local and systemic upset in the young child. Many therapies are on the market to help alleviate the symptoms of primary tooth eruption. In this article we highlight the problems of "teething" as a diagnosis by presenting a case where an initial misdiagnosis of teething compromised a patient's life. The same patient then suffered from topical analgesic misuse during the recovery period.
Dysfunctional uterine bleeding, although not usually life-threatening, can cause disruption and discomfort for many women. It has often been poorly researched in the past, possibly because of the difficulty in measuring menstrual blood loss. Several different therapies are available and individual women can choose from a number of options. Nonsteroidal anti-inflammatory drugs such as mefenamic acid or indomethacin will be the first choice for many women as they have few side effects and it is only necessary to take them when menstrual bleeding occurs. When contraception is also required, combined oral contraceptives are helpful. Progestogen and danazol therapy are also effective, although side effects do occur. A new development has been the levonorgestrel-containing intrauterine contraceptive device which has been shown to result in large decreases in menstrual blood loss. For those women who would like a surgical approach but do not want to undergo hysterectomy, the relatively new technique of endometrial resection results either in amenorrhoea or reduced menstrual blood loss in the majority of women.
To assess the effectiveness of commencing the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatments for women presenting with HMB in general practice.
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Bidirectional transport studies were performed using Caco-2 cells. Compounds exhibiting an efflux ratio of > or =2 were further examined for their potential interaction with P-gp and multidrug resistance-associated protein (MRP) using verapamil and indomethacin. Calcein efflux inhibition studies were conducted to investigate the efflux mechanism of these compounds. Geometry optimization of the esters was performed, and the spatial separation of two electron donor groups of each prodrug was measured.
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Hepatotoxicity is one of the common side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). We investigated the cytotoxicity of 18 acidic NSAIDs (3 salicylic acids, 3 anthranilic acids, 6 arylacetic acids, 6 arylpropionic acids) to freshly isolated rat hepatocytes as assessed by the NSAID-induced leakage of lactate dehydrogenase (LDH) in order to determine structural requirements for the direct hepatotoxicity of the NSAIDs. Diflunisal (salicylic acids), flufenamic acid, mefenamic acid, tolfenamic acid (anthranilic acids), diclofenac, indomethacin, acemetacin (arylacetic acids) and flurbiprofen (arylpropionic acids) caused significant LDH leakage, indicating that substituent position of a carboxyl group does not relate to the hepatotoxicity of the NSAIDs. Because the cytotoxic NSAIDs were of two types as classified by their "skeleton," diphenyl and diphenylamine, we tested the cytotoxicity of the compounds. Diphenyl did not cause LDH leakage, but diflunisal, which has the diphenyl structure, was cytotoxic. On the other hand, diphenylamine induced LDH leakage to the same degree as diclofenac, which has the diphenylamine structure. Therefore, diphenylamine itself was suggested to be responsible for the cytotoxicity of diclofenac and anthranilic acids, whereas a substituted group(s) in addition to diphenyl structure seems to be important for diflunisal cytotoxicity. All of the cytotoxic NSAIDs and diphenylamine extensively decreased hepatocellular ATP content, whereas the noncytotoxic NSAID did not, indicating that the NSAID-induced decrease in ATP, probably by their uncoupling effects on mitochondrial oxidative phosphorylation, is involved in the hepatotoxicity of the NSAIDs.
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The efficiency of sequential advanced membrane technology wastewater treatment plant towards removal of a widely used non-steroid anti-inflammatory drug (NSAID) mefenamic acid was investigated. The sequential system included activated sludge, ultrafiltration by hollow fibre membranes with 100 kDa cutoff, and spiral wound membranes with 20 kDa cutoff, activated carbon and a reverse osmosis (RO) unit. The performance of the integrated plant showed complete removal of mefenamic acid from spiked wastewater samples. The activated carbon column was the most effective component in removing mefenamic acid with a removal efficiency of 97.2%. Stability study of mefenamic acid in pure water and Al-Quds activated sludge revealed that the anti-inflammatory drug was resistant to degradation in both environments. Batch adsorption of mefenamic acid by activated charcoal and a composite micelle (otadecyltrimethylammonium (ODTMA)-clay (montmorillonite) was determined at 25.0°C. Langmuir isotherm was found to fit the data with Qmax of 90.9 mg g(-1) and 100.0 mg g(-1) for activated carbon and micelle-clay complex, respectively. Filtration experiment by micelle-clay columns mixed with sand in the mg L(-1) range revealed complete removal of the drug with much larger capacity than activated carbon column. The combined results demonstrated that an integration of a micelle-clay column in the plant system has a good potential to improve the removal efficiency of the plant towards NSAID drugs such as mefenamic acid.
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A simple, rapid, and highly sensitive method for simultaneous analysis of anti-inflammatory drugs (naproxen, ibuprofen, and mefenamic acid) in diluted human serum was developed using the electrochemically controlled solid-phase microextraction coupled to ion mobility spectrometry. A conducting molecularly imprinted polymer film based on polypyrrole was synthesized for the selective uptake and release of drugs. The film was prepared by incorporation of a template molecule (naproxen) during the electropolymerization of pyrrole onto a platinum electrode using cyclic voltammetry method. The measured ion mobility spectrometry intensity was related to the concentration of analytes taken up into the films. The calibration graphs (naproxen, ibuprofen, and mefenamic acid) were linear in the range of 0.1-30 ng/mL and detection limits were 0.07-0.37 ng/mL and relative standard deviation was lower than 6%. On the basis of the results obtained in this work, the conducting molecularly imprinted polymer films as absorbent have been applied in the electrochemically controlled solid-phase microextraction and ion mobility spectrometry system for the selective clean-up and quantification of trace amounts of anti-inflammatory drugs in human serum samples. Scanning electron microscopy has confirmed the nano-structure morphology of the polypyrrole film.
The MICs of diclofenac, mefenamic acid, ibuprofen, and naproxen, in the presence of PAβN, were significantly (≥4-fold) reduced, decreasing to 25-1600 mg/L, against the majority of the studied strains. In the case of acetylsalicylic acid only for 5 and 7 out of 12 strains of P. mirabilis and E. coli, respectively, a 4-fold increase in susceptibility in the presence of PAβN was observed. The presence of Aspirin resulted in a 4-fold increase in the MIC of ofloxacin against only two strains of E. coli among 48 tested clinical strains, which included species such as E. coli, K. pneumoniae, P. aeruginosa, and S. maltophilia. Besides, the medicinal products containing the following NSAIDs, diclofenac, mefenamic acid, ibuprofen, and naproxen, did not cause the decrease of clinical strains' susceptibility to antibiotics.
In the present work, the effect of application of voltage steps on extraction efficiency of pulsed electromembrane extraction (PEME) was investigated for the first time. The effects of voltage variations including initial and final voltages, number of steps between the initial and final voltages as well as their time durations were studied on the extraction efficiencies of three different classes of analytes. These classes include amitriptyline (AMI) and nortriptyline (NOR) as more hydrophobic analytes, diclofenac (DIC) and mefenamic acid (MEF) as acidic drugs and salbutamol (SB) and terbutaline (TB) as hydrophilic compounds. It was anticipated that the application of high voltages is not necessary at the beginning of the extraction, since large amounts of target analytes exist around the supported liquid membrane (SLM)/sample solution interface. So, they could be easily transferred into the acceptor phase utilizing lower voltages. Results showed that the benefits of voltage-step PEME (VS-PEME) are more obvious in systems with low electrical resistance (regarding the SLM composition). Efficiencies of VS-PEME for extraction of AMI and NOR (96% and 89% for AMI and NOR, respectively) were comparable with those achieved from applying a constant voltage (95% for AMI and 83% for NOR). However, recoveries from the VS-PEME of DIC and MEF (53% and 44% for DIC and MEF, respectively) were significantly higher than those from the application of a constant voltage (33% for DIC and 31% for MEF). Also, recoveries obtained from the VS-PEME for SB and TB were approximately 3 orders of magnitude greater than those from a constant voltage. Moreover, it was demonstrated that in all cases analytes could effectively be extracted at the beginning of extraction by applying low voltages.
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To determine the effectiveness and safety of prophylactic ibuprofen compared to placebo/no intervention or other cyclo-oxygenase inhibitor drugs (indomethacin, mefenamic acid, etc) in the prevention of PDA in preterm infants.