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Dysfunctional uterine bleeding is defined as abnormal uterine bleeding in the absence of organic disease. It is the result of anovulation or the abnormal local production of prostaglandins (PGs), and in each case, the primary fault is inappropriate hormone formation. There are 2 approaches to diagnosis. The traditional one is primarily concerned with the exclusion of cancer of the endometrium; this concern results in the frequent resort to uterine curettage. The 2nd approach is to limit curettage to patients whose symptoms are not ameliorated by medical therapy. The aim of the medical treatment is either to produce secretory change in the endometrium or to decrease the formation of uterine PGs. Intermittent progesterone treatment is used to cause secretory changes in the endometrium. Decreased production of the PGs is achieved indirectly by causing strophy of the endometrium or directly through the use of PG synthetase inhibitors. Surgery in the form of dilatation and curettage has no longterm therapeutic effect; hysterectomy is definitive therapy. (author's)
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To determine whether an educational package could influence the management of menorrhagia, increase the appropriateness of choice of non-hormonal treatment, and reduce referral rates from primary to secondary care.
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Some hydrogel dressings have been investigated to determine their utility for the treatment of painful dry tooth-socket (Alveolitis sicca dolorosa). As drugs mefenamic acid and Nipagin P have been applied. Hydrophilized methylcellulose, 5-15% glycerol or 5-20% PEG 200 were the filling and gel building material. It has been found, that the properties of the dressings depend on the content of the hydrophilizers. The half liberation time of the drugs under study ranges from 0.5 to 11 h, the swelling degree amounts to 366-400%, the washing out time runs to 80-140 min and the period of activity of the dressings inside the tooth-socket amounts to 24-48 h. The dressings show thixotropic properties and a high flow limit.
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Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used anti-inflammatory therapeutic agents, among which the fenamate analogues play important roles in regulating intracellular Ca²⁺ transient and ion channels. However, the effect of NSAIDs on TRPC4 and TRPC5 is still unknown. To understand the structure-activity of fenamate analogues on TRPC channels, we have synthesized a series of fenamate analogues and investigated their effects on TRPC4 and TRPC5 channels. Human TRPC4 and TRPC5 cDNAs in tetracycline-regulated vectors were transfected into HEK293 T-REx cells. The whole cell current and Ca²⁺ movement were recorded by patch clamp and calcium imaging, respectively. Flufenamic acid (FFA), mefenamic acid (MFA), niflumic acid (NFA) and diclofenac sodium (DFS) showed inhibition on TRPC4 and TRPC5 channels in a concentration-dependent manner. The potency was FFA>MFA>NFA>DFS. Modification of 2-phenylamino ring by substitution of the trifluoromethyl group in FFA with F, CH₃, OCH₃, OCH₂CH₃, COOH, and NO₂ led to the changes in their channel blocking activity. However, 2-(2'-methoxy-5'-methylphenyl)aminobenzoic acid stimulated TRPC4 and TRPC5 channels. Selective COX1-3 inhibitors (aspirin, celecoxib, acetaminophen, and indomethacin) had no effect on the channels. Longer perfusion (> 5 min) with FFA (100 μM) and MFA (100 μM) caused a potentiation of TRPC4 and TRPC5 currents after their initial blocking effects that appeared to be partially mediated by the mitochondrial Ca²⁺ release. Our results suggest that fenamate analogues are direct modulators of TRPC4 and TRPC5 channels. The substitution pattern and conformation of the 2-phenylamino ring could alter their blocking activity, which is important for understanding fenamate pharmacology and new drug development targeting the TRPC channels.
A triple-concentric time-controlled release mefenamic acid (MA) tablet was developed using Carbopol and Ethocel polymers. The burst dose was programed to release immediately after an ingestion of tablet to be followed by a lag period of 2-4 h, and thereafter an 8 h controlled release of MA from core tablet. Core tablets were prepared using Carbopols 971P, 974P, 71G or 907 at various concentrations. The core tablet provided a controlled release of MA and the release rate decreased with increasing polymer concentration. Highly cross-linked Carbopol 974P released MA at a faster rate compared to release from Carbopol 971P with medium degree of cross-linking. Carbopols 71G and 971P exhibited essentially similar release rates. Carbopol 907, a linear polymer, showed fastest release of MA. The extent of uptake of dissolution medium by core tablets was inversely related to the rate of release of MA from the tablets. Compression coating of core tablet with Ethocel provided the lag period to delay release of MA from core tablet. Increase in lateral coating thickness decreased MA release and increased lag period. Compression forces applied during compression coating with Ethocel for lag period, and immediate-release MA coating for burst release did not affect the integrity of core tablet.
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Wratizolin, the new non-steroidal anti-inflammatory drug, was found to inhibit the replication of Herpes simplex, type 1 and 2, viruses (HSV-1, HSV-2) in vitro. The selectivity of the antiviral action is low because the drug disturbs cellular metabolism. Wratizolin at the relatively low concentration (37 micrograms/ml) inactivates partially purified HSV-2 after incubation for 30 min at 37 degrees. The addition of albumin to the reaction mixture inhibits the virucidal activity of the drug. Wratizolin has little if any effect on the production and action of interferon. The drug used topically as 2% solution in dimethylsulfoxide inhibits the evolution of lesions induced in the guinea pig skin by HSV-2. However, the drug did not prevent the replication of HSV-2 in the guinea pig skin.
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Previous studies of interactions between warfarin and NSAIDs or reports of adverse interactions were identified from a MEDLINE search (1976 to present) and from the reference lists of pertinent articles.
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The 33-year-old woman was violently beaten and suffered from concussion of the upper abdomen. Because of pain she took mefenamic acid for two days. Then she reported hematemesis, melena and vertigo. The value for hemoglobin was determined as 5.8 g/dl. Acute blood loss was suspected, but neither intraabdominal nor upper gastrointestinal hemorrhage could be detected. Further investigations revealed a Coombs-negative hemolytic anemia and thrombocytopenia, and microangiopathic hemolysis was suggested by the detection of fragmentocytes in a peripheral blood smear. The diagnosis of thrombotic thrombocytopenic purpura (TTP) was made, though the patient did not suffer from manifestations of impaired microcirculation like neurological symptoms or renal failure. The TTP was found to be associated with HIV infection. The hematological disease responded well to the treatment with fresh-frozen plasma.
The study inclusion criteria were adults with: 1) NSAID hypersensitivity; 2) nasal polyposis/chronic rhinosinusitis; 3) not well-/poorly controlled asthma and 4) exposure to tNSAID. Patients were given verbal and written instructions to cease tNSAIDs exposure and asthma control was evaluated during the 6 months prior and after intervention.
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1. The contractile effects of tea polyphenols (TP) and its four principle catechins, namely (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG), on rat aorta contractility were investigated using the isometric tension recording technique. 2. At concentrations of 5-100 mg/L, TP evoked phasic contraction of rat aorta in a concentration-dependent but endothelium-independent manner. Of the four catechins tested, EGCG and EGC (3-300 micromol/L), but not EC and ECG, mimicked the contractile response to TP, suggesting that the epigallol moiety in the B ring may be associated with the contractile effect. 3. Contractions in response to EGCG and EGC were not affected by several endogenous vasoconstrictor receptor antagonists, but could be abolished by 10 micro mol/L BAPTA-AM, a membrane-permeable Ca2+ chelator, or attenuated by removal of extracellular Ca2+, suggesting the involvement of both intracellular and extracellular Ca2+ in evoking the contraction. 4. Pretreatment with non-selective Ca2+ channel antagonists mefenamic acid (10 micro mol/L), tetrandrine (30 micro mol/L) and SKF 96365 (30 micromol/L), but not nifedipine (1 micromol/L), the selective inhibitor of voltage-dependent Ca2+ channels, inhibited the contractile responses to EGC and EGCG, indicating the involvement of Ca2+ influx via non-voltage dependent Ca2+ channels. 5. Several intracellular Ca2+ channel modulators, including procaine (5 mmol/L), dantrolene (30 micromol/L) and 2-amino ethoxydiphenyl borate (50 micromol/L; an inositol 1,4,5-trisphosphate receptor inhibitor), also inhibited EGCG- and EGC-induced contractions, thus suggesting a role of intracellular Ca2+ release in these contractions. 6. Both EGCG- and EGC-induced contractions were depressed, to different degrees, by inhibitors of several receptor-coupled enzymes, including phospholipase C, protein kinase C, phospholipase A2 and tyrosine kinase. Furthermore, both EGCG- and EGC-induced contractions were completely abolished by catalase, but not by superoxide dismutase or mannitol/dimethyl sulphoxide. 7. Taken together, these data show, for the first time, that TP and its related catechins that contain an epigallol structure in the B ring, as in EGCG and EGC, exert direct contractile effects on rat aortic smooth muscle via a H2O2-mediated pathway.
The prevailing self-medication practices were inappropriate in a substantial proportion of women with inadequate knowledge regarding appropriate drug choice, therapeutic doses, and their associated side effects.
All pills analyzed contained mefenamic acid and diazepam. Complications related to the presence of these substances included, among others, massive gastrointestinal bleeding.
Self-emulsifying drug delivery systems (SEDDS), whereby drugs are dispersed in an oil-surfactant mix that emulsifies on contact with water, represent a highly promising approach for enhancing oral bioavailability. However, the choice of formulation is, at present, largely empirical both in terms of the composition dependence of the emulsification process and the solubilisation of the drug in the initial oil-surfactant mixture. In this investigation, a range of chemically related self-emulsifying systems have been studied, based on the Labrafil family of polyglycolysed oils, using Tween 80 and Tween 20 as surfactants. The ease of emulsification, the particle size distribution and the appearance of the emulsion droplets were studied as a function of composition, while the solubility of danazol and mefenamic acid in the various oil-surfactant mixes was measured. It was noted that dilution of the emulsions led to apparent change in particle size distribution. The more hydrophilic oil-surfactant mixes showed a greater ease of emulsification and a lower particle size. It was also noted that multiple emulsions could be formed using systems of lower polarity. A linear relationship was observed between the hydrophile-lipophile balance (HLB) of the mix and the solubility of both danazol and mefenamic acid, with more hydrophilic mixes showing greater drug solubility values. The study has indicated that, within the range studied, more hydrophilic mixes tend to result in superior emulsification properties and greater drug solubility.
Office hysteroscopy with endometrial biopsy is usually the first investigation for abnormal uterine bleeding and other uterine diseases.