The purpose of this study was to compare the effect of long-term ouabain treatment on the vascular reactivity and Na+, K+-ATPase activity of a conductance artery from normotensive and hypertensive rats.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) are major factors in gastritis and peptic ulcer However, the role of NSAIDs and H. pylori infection in dyspepsia remains unclear. Gastric adaptive relaxation may be related to the pathogenesis of functional dyspepsia because the response is often disturbed in dyspeptic patients. In this study, we investigated the effects of indomethacin or H. pylori water extracts on gastric adaptive relaxation. This experiment was performed using the modified method of Desai et al. Isolated guinea-pig stomach in an organ bath was monitored for intragastric pressure and volume. Adaptive relaxation was induced by gastric luminal distention. The effects of indomethacin and H. pylori on gastric relaxation were tested in this system. Indomethacin (> 1 x 10(-5) M) significantly inhibited adaptive relaxation. Indomethacin (> 3 x 10(-6) M) induced gastric relaxation in a dose-dependent fashion. However, aspirin at a concentration sufficient for cyclooxygenase (COX)-1 inhibition did not induce gastric relaxation. Preincubation with N-nitro-L-arginine methyl ester, a nitric oxide (NO)-synthase inhibitor, inhibited indomethacin-induced gastric relaxation. Adaptive relaxation was not affected by H. pylori water extracts. In conclusion, indomethacin inhibited adaptive relaxation via prior gastric relaxation. NO production, but not COX-1 inhibition, may be involved in this effect of indomethacin. H. pylori water extracts may not have direct effects on adaptive relaxation. Inhibition of adaptive relaxation may be one of the major mechanisms underlying NSAID-induced dyspepsia.
Of 41 extremely-low-birth-weight infants with PDA, 3 infants had spontaneous closure and 3 died before treatment. Of the remaining 35 infants, 13 received enteral ethanol solution of indomethacin and 22 received the intravenous (IV) form. The total closure rates of the IV and enteral groups were 81.8% and 76.9%, respectively. There were no significant differences in the incidence of impaired renal function, necrotizing enterocolitis, chronic lung disease or severe retinopathy of prematurity between the 2 groups.
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Prophylactic use of ibuprofen reduces the incidence of PDA. However, further trials, which address potential adverse effects including pulmonary hypertension, are needed. Such trials should include long-term neurodevelopmental outcomes. Trials comparing the effectiveness of prophylactic use of indomethacin versus ibuprofen may be warranted with particular reference to IVH, need for surgical ligation and neurodevelopmental outcome.
To evaluate the quality of life in patients with facial steroid dermatitis before and after the treatment of doxycycline and indomethacin plus support therapy.
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The half-lives of typical acute phase proteins in rats and beagle dogs during acute inflammation were investigated. Acute inflammation was induced by injection of turpentine oil in rats and administration of indomethacin in beagle dogs. Serum concentrations of α2-macroglobulin (α2M) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay and α1-acid glycoprotein (AAG) was measured by single radial immunodiffusion. Half-life was calculated as 0.693/elimination rate constant (K). The mean half-lives in the terminal elimination phase of α2M and AAG were 68.1 and 164.8 h, respectively. The half-life of AAG was significantly longer than that of α2M. Mean half-lives in the terminal elimination phase of CRP and AAG were 161.9 and 304.4 h, respectively. The half-life of AAG was significantly longer than that of CRP in beagle dogs. No significant differences in the half-life of AAG were observed between rats and beagle dogs. Furthermore, serum concentrations in the terminal elimination phase could be simulated with the K data acquired in this study.
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Tribulus terrestris has been used in traditional medicine for relieving rheumatic pain and as an analgesic plant for a long time. In this investigation the analgesic effect of methanolic extract of this plant on male albino mice was evaluated by formalin and tail flick test. Extraction of the fruits of the plant was done by two different methods (suxheletion and percolation) with methanol 80%. The percolated extract was injected intraperitoneally in mice at 50, 100, 200, 400, and 800 mg/kg. The results showed that a dose of 100 mg/kg of percolated extract had the highest significant analgesic effect compared to the control group (P < 0.01) in formalin and tail flick test. There is no significant difference in the analgesic effect of suxheleted and percolated extract. The analgesic effect of the extract was lower than morphine, 2.5 mg/kg in both tests, and higher than ASA 300 mg/kg in chronic phase of pain in formalin test (P < 0.05). Pretreatment of animal with naloxone did not change the analgesia induced by the plant extract in both tests, therefore the involvement of opioid receptor in the analgesic effect of this plant was excluded. The results of ulcerogenic studies indicate that the gastric ulcerogenecity of plant extract is lower than the indomethacin in the rat's stomach. It can therefore be concluded that T. terrestris extract has a suitable analgesic effect and further studies are required to produce a more effective product of this plant to substitute for conventional analgesic drugs.
Ws/Ws rats and control (W+/W+) rats were given indomethacin (15 mg/kg) subcutaneously, and the intestinal mucosal damage was estimated after 24 h.
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Post-dural (post-lumbar or post-spinal) puncture headache (PDPH) is one of the most common complications of diagnostic, therapeutic or inadvertent lumbar punctures. Many drug options have been used to prevent headache in clinical practice and have also been tested in some clinical studies, but there are still some uncertainties about their clinical effectiveness.
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This study provides Class I evidence that in ED patients with acute migraine, IV valproate is inferior to metoclopramide or ketorolac in improving headache outcomes.
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Collagen-mediated adhesion is a multifaceted event requiring multiple receptors and platelet-derived soluble agonists. We investigated the influence of NO on these processes.
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A novel injectable formulation of diclofenac, Dyloject, utilizes hydroxypropyl-β-cyclodextrin (HPβCD) as a solubilizing agent, allowing dosing as a small-volume intravenous bolus for postoperative pain. In this test of the efficacy and safety of HPβCD diclofenac, we hypothesized that HPβCD diclofenac would relieve moderate and severe pain after orthopedic surgery.
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FIMA showed high inhibitory potency and selectivity for COX-2. Radioiodinated FIMA showed specific accumulation into COX-2 induced macrophages, no significant in vivo deiodination and rapid blood clearance. Radioiodinated FIMA deserves further investigation as a SPECT radiopharmaceutical for imaging COX-2 expression.
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The highest level of endothelin-1 was found in the radial artery. Endothelin-1 contracted both arteries. The contraction was sensitive to endothelinA-receptor agonism and enhanced in both arteries by inhibition of prostacyclin and nitric oxide formation. In the internal mammary artery the endothelinB-receptor agonist caused an endothelinA-receptor sensitive contraction augmented by inhibition of nitric oxide and prostacyclin. However, in the radial artery this contraction was only observed in the presence of inhibition of nitric oxide and prostaglandin.
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Either 0.5% or 0.25% preservative-free ketorolac tromethamine ophthalmic solution (0.1 mL) was injected into the vitreous of the right eye of 15 rabbits. Physiologic saline solution (BSS; Alcon, Ft. Worth, TX) was injected into the left eye of each rabbit as a control. A standard electroretinogram and intraocular pressure measurements were obtained before injection, and repeated 1 day and 1, 2, 3, and 4 weeks after injection. After 4 weeks, the rabbits were euthanatized and the retinas examined by light and electron microscopy. Differences in the electroretinograms, intraocular pressure, and histopathology between the two eyes were recorded. Further, the elimination half-life of the drug in the vitreous was assessed.
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A prospective, randomized, and parallel-group study.
Although generally well-tolerated, rilonacept in combination with indomethacin and rilonacept alone did not provide additional pain relief over 72 hours relative to indomethacin alone in patients with acute gout flare.
The MBF response to acetylcholine was significantly lower in CBDL and tended to be lower in PPVL than in sham. L-NAME and indomethacin significantly decreased the MBF response to acetylcholine in all groups. The hyporeactivity to acetylcholine in CBDL and PPVL was maintained after L-NAME and indomethacin. The MBF response to pinacidil, deta-NONOate and phenylephrine, before and after NO synthase and cyclo-oxygenase inhibition, was lower in CBDL and PPVL than in sham.
Following the new IHS classification, cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT syndrome) are included in the classification as trigeminal autonomic cephalgias (TAC). The similarities of these syndromes suggest a considerable shared pathophysiology. These syndromes have in common that they involve activation of trigeminovascular nociceptive pathways with reflex cranial autonomic activation. Clinically, this physiology predicts pain with some combination of lacrimation, conjunctival injection, nasal congestion, or eyelid edema. Broadly the management of TAC comprises acute and prophylactic treatment. Some types of trigeminal autonomic headaches such as paroxysmal hemicrania and hemicrania continua have, unlike cluster headaches, a very robust response to indomethacin, leading to a consideration of indomethacin-sensitive headaches. This review covers the clinical picture and therapeutic options. Although studies following the criteria of evidence-based medicine (EBM) are rare, most patients can be treated sufficiently.
Hemicrania continua (HC) is a primary headache disorder characterized by a continuous, unilateral headache that varies in intensity, waxing and waning without disappearing completely. Ipsilateral cranial autonomic features and response to indomethacin are essential features for the diagnosis of HC. We hereby, describe three patients with the clinical phenotypes of HC in whom response to indomethacin was either incomplete or not sustained. We also review the literature especially for the presence of indomethacin response and ipsilateral cranial autonomic features.
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Various NSAIDs are being used in newborns. Indomethacin and ibuprofen are used worldwide for closure of patent ductus arteriosus (PDA). Both have been tested in randomized clinical trials and are approved by FDA and EMEA for PDA closure in newborns. Indomethacin, but not ibuprofen is used for prevention of intraventricular hemorrhage (IVH). Ketorolac is being studied as a potential parenteral analgesic and as a topical drug for prevention of oxygen-induced retinopathy. Others are associated with severe adverse events.
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The aim of the current study was to investigate the role of arachidonic acid (AA) metabolism via cyclooxygenase (COX) in the endothelial dysfunction of penile arteries from pre-diabetic, obese Zucker rats (OZR).
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Observations were carried out in 98 normal healthy human subjects and in 178 patients with different gastrointestinal diseases (gastritis, erosions, ulcer, polyps, cancer, inflammatory bowel diseases, colorectal polyps, cancers). The gastric secretory responses and their chemical composition, gastric emptying, sugar loading test, gastric transmucosal potential difference (GTPD) were investigated following with administration of (a) capsaicin alone, (b) ethanol alone or with capsaicin, and (c) indomethacin-induced gastric mucosal microbleeding with or without capsaicin, both before and after 2 weeks capsaicin treatment. Immunohistochemical investigations were performed to establish the presence of the capsaicin (vanillinoid) receptor (TRVP1), CGRP and SP in the whole GI tract. Conventional molecular pharmacological methods were applied to study the effects of capsaicin and other drugs for their inhibitory effects on the gastric basal acid output.