The in vivo responsiveness of small arterioles to the topical administration of two parathyroid hormone fragments was investigated using television microscopy. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital (50 mg/kg) and second- and third-order arterioles in the cremaster muscle were exposed to increasing concentrations (2 X 10(-5) to 6 X 10(-4) mg/ml) of either hPTH (1-34) or bPTH-(3-34). Second- and third-order arterioles within the cremaster dilated (183% and 281% of control, respectively) following exposure to PTH-(1-34) in bath concentration of 10(-4) mg/ml and above. The dilation associated with PTH administration was abolished in second-order and greatly attenuated for third-order arterioles when the first two amino acid residues of the PTH molecule were removed (PTH (3-34) fragment). Inhibition of endogenous prostaglandins synthesis with mefenamic acid did not attenuate the vasodilator response to PTH. However, exposure to the muscarinic blocking agent atropine (10(-7) g/ml) totally inhibited the dilator response to PTH-(1-34). These data suggest that PTH induces arteriolar dilation by stimulation of muscarinic receptors in the vasculature possibly by causing the release of endogenous acetylcholine.
To investigate the management of menorrhagia in primary care and its impact on referral and hysterectomy rates.
These studies evaluate the susceptibility of the Syrian hamster to the induction of renal papillary lesions after exposure to 2-bromethylamine (2-BEA), mefenamic acid, indomethacin, acetaminophen and phenylbutazone. In most cases there were 25 animals per dose group. Papillary necrosis was produced by single or multiple ip doses of 75 mg 2-BEA/kg and above, and was present within 12 hr of administration of a dose of 500 mg/kg body weight. There were lesions in the renal papilla of hamsters 10 days after a single dose of 500 mg 2-BEA/kg. The severity of papillary lesions increased up to 4 days after exposure in hamsters given a single dose of either 250 or 500 mg 2-BEA/kg. The severity of papillary lesions did not increase with the number of doses in hamsters given multiple doses (2-5) of 100 mg 2-BEA/kg. Renal papillary necrosis was observed in about 40% of hamsters given 100, 200 or 400 mg mefenamic acid/kg. Only a few of the hamsters given indomethacin had renal papillary lesions and none of those given acetaminophen (up to 400 mg/kg) or phenylbutazone (up to 600 mg/kg) developed renal papillary lesions.
A quantitative method for measuring pain threshold by the use of ultrasonic stimulation in man was designed and the possibility of clinical application in assessing analgesics was investigated. Ultrasonic stimulus was given to Japanese subjects on the palmer distal part of the 2nd, 3rd and 4th fingers of both hands. The latent time between start of the stimulation and withdrawal of the hand when perceiving pain was considered the pain threshold. The ultrasonic evoked pain was a sharp pin-prick type, without sensations such as thermal and mechanical. The pain threshold lowered with increasing either stimulus intensity or water bath temperature when the hand of the subject was immersed during measurement. Normal threshold to ultrasonic stimulation measured in both 50 men and 50 women gave nearly normal distribution curves; women being more sensitive to ultrasonics than men. Analgesia with codeine phosphate (20 mg p.o.), aspirin (1.5, 1.0, 0.5 g p.o.), aminopyrine (100 mg p.o.) and mefenamic acid (500 mg p.o.) in volunteers of both sexes was demonstrated significantly using this method under double blind circumstances. Pentobarbital, diazepam, butylscopolamine, bromelain and placebo each in the usual dose used clinically failed to alter the pain threshold. Humans were at least 25 fold more sensitive than mice to the analgesics used herein.
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Patients with aspirin-exacerbated respiratory disease (AERD) also recently known as nonsteroidal anti-inflammatory drug (NSAID) exacerbated respiratory disease (NERD) must avoid aspirin and all other oral NSAIDs. The effect of topical NSAID (tNSAID), especially salicylates which are commonly present in topical medicated preparations, on asthma control of this phenotype is studied.
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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Fixed drug eruption is a fairly common drug-induced hypersensitivity reaction of the skin and the mucous membranes, which is characterized by the re-occurrence of the lesion(s) exactly on the previously involved sites after repeated administration. The pathogenetic mechanisms of this site-specificity are not fully elucidated.
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In this study, electrospun nanofibers were used as solid-phase microextraction (SPME) fiber coatings after substituting the water-soluble sheath of the emulsion electrospun polystyrene (PS)@Plurinic F-127 core-sheath nanofibers with biocompatible and water-stable polydopamine (PDA) and subsequently being appropriately cross-linked with glutaraldehyde (GA) to enhance the strength of the electrospun architecture. The novel custom-made PS@PDA-GA coating was wettable in aqueous solutions and thus exhibited much higher extraction efficiency than the nonsheathed PS nanofiber coating and the thicker polydimethylsiloxane (PDMS) coating. The novel coating also possessed excellent stability (relative standard deviations (RSDs) less than 7.3% for six sampling-desorption cycles), interfiber reproducibility (RSDs less than 14.3%), and antibiofouling ability, which were beneficial for in vivo sampling. The PS@PDA-GA fiber was used to monitor pharmaceuticals in dorsal-epaxial muscle of living fish, and satisfactory sensitivities with the limits of detection in the range of 1.1 (mefenamic acid) to 8.9 (fluoxetine) ng·g(-1) and comparable accuracies to liquid extraction were achieved. In general, this study explored a convenient and effective method to sheath nanofibers for high-efficient in vivo SPME of analytes of interest in semisolid tissues.
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The data regarding net benefit/harm are insufficient to make a conclusion as to whether surgical ligation or medical treatment with indomethacin is preferred as initial treatment for symptomatic PDA in preterm infants. It should be noted that three recent observational studies indicated an increased risk for one or more of the following outcomes associated with PDA ligation; chronic lung disease, retinopathy of prematurity and neurosensory impairment . It is possible that the duration of the "waiting-time" and transport to another facility with surgical capacity to have the PDA ligated could adversely affect outcomes, as could the perioperative care.
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Transglycosylated stevia (stevia-G) can effectively improve the dissolution and bioavailability of poorly water-soluble drugs. Furthermore, addition of an ionic surfactant to stevia-G solution has been shown to enhance the dissolution effect of stevia-G on flurbiprofen. Herein, 4 surfactants, namely sodium dodecyl sulfate, sodium N-dodecanoylsarcosinate, sodium monododecyl phosphate, and lauryltrimethylammonium chloride (LTAC) were screened to investigate their synergistic effect with stevia-G in enhancing the solubility of mefenamic acid (MFA). The ternary formulation containing LTAC produced the highest increase in solubility, whereas the binary MFA/LTAC formulation did not increase the solubility of MFA. Surface tension was evaluated to analyze the interaction between stevia-G and each ionic surfactant, wherein the Rubingh model was applied to predict mixed micelle formation between stevia-G and LTAC. Interaction parameters calculated by the Rubingh model reflected mixed micelle formation between stevia-G and LTAC relative to the self-interactions of the 2 individual surfactants. All interaction parameters in this system showed negative values, indicating a favorable interaction (e.g., hydrogen bond or electrostatic and dipole) between binary components in the mixed micelles. Spray-dried particles of ternary formulations (MFA/stevia-G/LTAC) were prepared to evaluate the dissolution profile and physicochemical properties. Dissolution profiling showed that the concentration of MFA released from spray-dried particles was significantly higher than untreated MFA.
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We found that the proportions of CD4+ and CD8+ T cells capable of producing IFN-gamma and IL-4 remained unchanged after challenge, while those of CD4+ and CD8+ T cells capable of producing IL-10 dramatically increased after challenge. The frequency of CD8+ T cells capable of producing IL-2 decreased after challenge.
Mefenamic acid and vitex agnus were both effective on IUD induced bleeding; however, mefenamic acid was more effective.
The major contribution of UGT1A9 towards arbidol glucuronidation was demonstrated in this study.
The results of this study suggested that aspirin use might reduce the risk of ALS, and the benefit might be more prominent for older people.
All studies which might describe randomised controlled trials of antifibrinolytic therapy for the treatment of heavy menstrual bleeding were obtained by electronic searches of MEDLINE 1966-1997, EMBASE 1980-1997 and the Cochrane Library. Companies producing antifibrinolytics and experts within the field were contacted for reference lists and information on unpublished trials.
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At least two review authors worked independently at each step of the original review, then compared results and resolved differences. The current update was conducted by one review author (AO). Methodological quality of eligible studies was assessed according to blinding of randomization, of intervention and of outcome assessment, and completeness of follow up. Weighted treatment effects, calculated using RevMan 4.2.10, included typical relative risk (RR), typical risk difference (RD), number needed to treat to benefit (NNT) or harm (NNH), and weighted mean difference (WMD), all with 95% confidence intervals (CI). A fixed effect model was used for meta-analyses. Heterogeneity tests including the I-squared test (I(2)) were performed to assess the appropriateness of pooling the data.
Oral mefenamic acid was administered 8 hours before the procedure. A combined cervical/paracervical block using lignocaine 1% adrenaline 1:200,000 was used before hysteroscopic endometrial ablation using the HTA device.
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The method was validated according to the recommendations of the Food and Drug Administration, including assessment of linearity, selectivity, precision, accuracy, and stability in human plasma. The use of betamethasone dipropionate as internal standard improved accuracy and precision. Response was linear over the calibration ranges. The limits of quantification were 0.2 g/mL for diflunisal and naproxen, 0.05 g/mL for ketoprofen, 0.1 g/mL for etodolac and mefenamic acid, and 0.02 g/mL for celecoxib and rofecoxib. The percent coefficient of variation for the QCs and the limit of quantification were within 10%, and the accuracies ranged between 96% and 106% for all the analytes. Mean drug recovery values were in the range of 95%-98% and 90.0% for all analytes and internal standard, respectively. All the analytes were stable in frozen plasma over a period of 3 months at -80°C.
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Dimaprit, a highly selective H2-agonist, caused a multiphasic contraction of guinea-pig ileal segments and ileal myenteric plexus-longitudinal muscle preparations. The initial phase was characterized by a twitch which reached a maximum in 15 to 30 sec and was followed by a partial relaxation. The later phase was variable and consisted of a series of twitch responses or of a slowly developing contracture which sometimes was accompanied by oscillatory changes in tension. dose-response curves were generated for the initial response; for isolated ileal segments the EC50 was 5.1 +/- 1.8 micrometers (mean +/- S.D., N = 7) and the Hill coefficient was 1.1 +/- 0.2 and for longitudinal muscle strips the EC50 was 5.8 +/- 1.2 micrometer and the Hill coefficient was 1.2 +/- 0.1 (N = 7). Both the initial and secondary components of the contractile responses to dimaprit were prevented by 0.2 micron tetrodotoxin or 10 microns mefenamic acid and by the production of tachphylaxis to either substance P or serotonin. Scopolamine, 0.001 to 0.1 micron, insurmountably antagonized only the initial component of the response. Mepyramine (1.0 micrometer), hexamethonium (100 microns), bromolysergic acid (0.25 microns) and p-(imidazol-1-yl)phenyl (10 microns) were without effect on the response to dimaprit. The histamine H2-receptor antagonist, tiotidine, produced parallel dextral shifts in the dose-response curve for dimaprit. The apparent pA2 value for tiotidine was 7.65. The results suggest that dimaprit acts on H2-receptors located on myenteric plexus neurons to cause the release of contractile substances. The mediators of the contractile response are tentatively identified as acetylcholine, substance P, serotonin and a product(s) of the arachadonic acid cascade.
Co-administration of SR extract and MEF potentiated the anti-inflammatory effects, alleviated the MEF-induced stomach adverse effect while having minimal pharmacokinetic interactions. Our findings provide insight for combination therapy of SR extract and MEF against inflammatory diseases.