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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. To investigate whether indomethacin affects basal glucose production, we measured hepatic glucose production in six healthy postabsorptive subjects on two occasions: once after administration of indomethacin (150 mg orally) and once after administration of placebo. 2. Glucose production was measured by primed, continuous infusion of [3-3H]-glucose. 3. Indomethacin administration resulted in an increase in glucose production from 10.9 (SEM 0.3) mumol min-1 kg-1 to a maximum of 16.5 (SEM 1.6) mumol min-1 kg-1 (P < 0.05) within approximately 1 h, whereas in the control experiment glucose production declined gradually (P < 0.01) (P < 0.05 indomethacin versus control). There were no differences in plasma concentrations of insulin, C-peptide and counter-regulatory hormones between the two experiments. 4. Since indomethacin administration resulted in an increase in glucose production in the absence of any changes in concentrations of glucoregulatory hormones, we conclude that indomethacin stimulates hepatic glucose production through other mechanisms.
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PMID:Indomethacin stimulates basal glucose production in humans without changes in concentrations of glucoregulatory hormones. 828 59

To study the involvement of local sensory nerves in reactive hyperemia, laser-Doppler measurements of skin blood flow were recorded in locally anesthetized and untreated forearm sites in eight volunteers after 90, 180, and 360 seconds of arrested forearm blood flow. The reactive hyperemia increased in magnitude and duration in response to increasing occlusion periods. However, maximum postocclusion flows in the untreated site of 31 +/- 5%, 38 +/- 6%, and 49 +/- 5% (mean +/- SEM) flux were significantly greater than the 14 +/- 3% (P < .005), 20 +/- 4% (P < .005), and 25 +/- 5% (P < .001) flux seen in the anesthetized sites. The duration of the hyperemia was also shortened from 139 +/- 26 seconds in the untreated site to 61 +/- 17 seconds (after the 360-second occlusion, P < .02) in the anesthetized sites. The anesthesia did not alter the increase in local blood flow induced by intradermally injected calcitonin gene-related peptide. Topically applied capsaicin induced a localized increase in blood flow that was unaffected by anesthesia and a surrounding flare that was abolished by the treatment. The results show that local anesthesia can significantly inhibit reactive hyperemia by a mechanism that does not alter the vasodilation induced by exogenous calcitonin gene-related peptide or the localized capsaicin-induced release of vasodilators from sensory nerves. Indomethacin was also found to be effective in suppressing reactive hyperemia. The evidence suggests that postocclusion reactive hyperemia in human forearm skin is mediated by a local reflex involving sensory nerves and a cyclooxygenase product, probably a vasodilator prostaglandin.
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PMID:Evidence for sensory nerve involvement in cutaneous reactive hyperemia in humans. 850 26

Eighteen preterm infants severely ill with respiratory distress syndrome who required assisted ventilaton were given modified natural surfactant (Survanta) endotracheally. They had a mean +/- SEM gestational age of 31.2 +/- 0.4 weeks (range 28-34) and a mean +/- SEM birthweight of 1562 +/- 71 g (range 1160-2010). Average time of initial surfactant administration was 15 +/- 1.7 hour (range 5-24). No significant side effects were found during surfactant instillation. Post surfactant, the air entry was improved, oxygenation and arterial/alveolar gradients increased, and the levels of inspired oxygen could be reduced. Some of the radiological abnormalities were resolved. In 13 infants, patent ductus arteriosus became clinically evident, seven of whom received Indomethacin. There were 4 cases of pulmonary air leak, 5 cases of pulmonary hemorrhage and 8 cases of bronchopulmonary dysplasia. Four infants expired, two were due to severe asphyxia/shock and two died of unrelated causes. Among the 14 survivors who came for follow-up, two cases of retinopathy of prematurity had gradually regressed, one had cerebral palsy and delayed development. Surfactant rescue therapy is a supplemental beneficial treatment for severe respiratory distress syndrome while newborn intensive care concept is necessary for efficient diagnosis and treatment of RDS.
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PMID:Surfactant treatment in the neonate with severe respiratory distress syndrome. 870 7

We evaluated the effect of inhaled indomethacin, a nonsteroidal antiinflammatory drug (NSAID), on exercise-induced bronchoconstriction (EIB) in children with asthma. Nine asthmatic children (7 boys, 2 girls, with a mean +/- SEM age of 11.0 +/- 0.8 yr) with a history of EIB participated in this study. These subjects were pretreated with inhaled indomethacin (3 mg/m2 body surface area [BSA]) or placebo (0.9% saline) according to a double-blind, randomized, crossover design, and underwent an exercise challenge test 15 min after the pretreatment. Inhaled indomethacin significantly attenuated EIB. The mean maximal percent decrease in FEV1 following exercise was 36.1 +/- 5.7% after placebo and 18.0 +/- 4.6% after indomethacin pretreatment (p = 0.0310). Indomethacin also significantly reduced the mean maximal decrease in arterial oxygen saturation after exercise (p = 0.0378). The inhibition of local prostaglandin synthesis and/or ion transport in the airways may be a mechanism involved in the protective potency of inhaled indomethacin.
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PMID:Effect of inhaled indomethacin on exercise-induced bronchoconstriction in children with asthma. 937 98

Radiocontrast agents and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for the diagnosis and treatment of renal colic. We studied their impact during unilateral acute urinary outflow obstruction upon renal microcirculation and parenchymal integrity. Laser-Doppler and ultrasonic regional flow measurements demonstrated selective decline of outer medullary blood flow by 23 +/- 2% during an acute increase of intra-pelvic pressure to 50 to 55 cm H2O (N = 28, X +/- SEM, P < 0.01). In rats preconditioned with indomethacin, this manipulation reduced medullary blood flow by 50 +/- 4% (N = 16, P < 0.01 vs. obstruction alone), with cortical and total renal blood flow declining by 18 +/- 4% and 16 +/- 2%, respectively (P < 0.01). Unilateral obstruction alone for 24 hours in intact rats resulted in injury (hemorrhage and necrosis) to the papilla and fornix (formed laterally by inner stripe and medially by the inner medulla). These changes were detected as early as 30 minutes after ureteral ligature by staining for fragmented nuclear DNA (TUNEL). Mild damage of thick ascending limbs (mTALs) was associated with substantial medial fornix injury. Indomethacin markedly increased mTAL injury in obstructed kidneys, but attenuated inner medullary damage, both in the medial border of the urinary space and at the papilla. This latter protective effect, probably mediated by the decrease in intrapelvic pressure, was blunted by concomitant intravenous fluid load. Contrast media (iothalamate) and L-NAME (N omega nitro-L-arginine methyl ester) both augmented inner stripe and inner medullary damage in hydronephrotic kidneys. In rats concomitantly subjected to radiocontrast, indomethacin and L-NAME (an acute renal failure protocol, J Clin Invest 94:1069, 1994), unilateral obstruction augmented inner stripe hypoxic damage (65 +/- 6% vs. 24 +/- 11% of mTALs in contralateral kidneys, N = 7, P < 0.01). Injury was maximal at the fornix (93 +/- 6% vs. 39 +/- 14% of mTALs in the mid-inner stripe, P < 0.01) and extended to the outer stripe and medullary rays. Thus, in the rat acute ureteral obstruction alters medullary blood flow and within 24 hours produces medullary damage in both forniceal and inner medullary locations, that is exacerbated by concomitant measures which limit medullary oxygenation. Contrast studies, forced hydration and NSAIDs for renal colic are potentially harmful and their use should be re-evaluated.
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PMID:Renal microcirculation and tissue damage during acute ureteral obstruction in the rat: effect of saline infusion, indomethacin and radiocontrast. 906 96

The mechanisms by which endothelium attenuates vasodilation caused by isoflurane are not well understood. We examined the role of endothelium-derived substances, nitric oxide (NO), endothelium-derived hyperpolarizing factors (EDHF), prostanoids and endothelins in the response to isoflurane in rat thoracic aorta. Increasing cumulative concentrations of isoflurane were administered to aortic rings suspended in Hepes solution and preconstricted with either phenylephrine 10(-6) mol litre-1 or KCl 40 mmol litre-1 (which inhibit EDHF). Rings were intact, denuded or incubated with an inhibitor of nitric oxide synthesis (N omega-nitro-L-arginine (LNNA 5 x 10(-5) mol litre-1), an inhibitor of prostanoid synthesis (indomethacin 10(-5) mol litre-1) or a blocker of the vascular receptors to endothelins (cyclo (-D-trp-D-Asp-Pro-D-Val-Leu (BQ 123 10(-5) mol litre-1)- Endothelium attenuated isoflurane-induced vasodilation in KCl-constricted rings at concentrations of 4% (mean 95 (SEM 4)% vs 72 (4)%; P = 0.0005) and 5% (100 (4)% vs 80 (4)%; P = 0.0008) and in phenylephrine constricted rings at concentrations of 4% (54 (8)% vs 35 (3)%; P = 0.04) and 5% (78 (10)% vs 49 (5)%; P = 0.03). Relaxation was significantly greater in rings treated with LNNA than in intact rings at concentrations of 4% (85 (4)% vs 72 (4)%; P = 0.0005) and 5% (90 (4)% vs 80 (4)%; P = 0.0008). Indomethacin and BQ 123 did not alter isoflurane-induced vasodilation. We conclude that endothelium attenuated the vasodilator effect of isoflurane by a mechanism which was abolished by inhibition of nitric oxide. We hypothesize that isoflurane inhibits the release of nitric oxide, leading to a relative vasoconstriction counter-balancing its vasodilator effect. In contrast, EDHF, prostanoids and endothelins were not involved in the attenuation of isoflurane-induced vasodilatation.
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PMID:Role of endothelium in the modulation of isoflurane-induced vasodilatation in rat thoracic aorta. 930 94

We have previously reported a reduction in exercise-induced hypoxaemia following polyunsaturated fatty acid supplementation (PUFA). Although this might have been explained by increases in membrane fluidity, a clear explanation could not be provided due to potentially confounding influences of series-2 prosta- glandin mediated effects resulting from PUFA. In this investigation, ten master athletes [mean age 48.1 (SEM 6) years, maximal oxygen uptake (VO2max) 3.39 (SEM 0.21) l x min(-1)] completed a maximal cycling test (Ctrl) which was repeated after the administration of 150 mg of indomethacin to inhibit prostaglandin synthesis, both before and after 6 weeks of 3.66-g PUFA x day(-1). Cardiorespiratory parameters were obtained simultaneously with brachial arterial blood sampling for partial pressure of oxygen in arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood (PaCO2), pH, oxygen saturation in arterial blood and lactate concentration determinations. A significant decrease in PaO2 (mmHg) from rest [93 (SEM 1.5)] was observed for exercise intensities of more than 40% VO2max in Ctrl reaching 75.9 (SEM 2.1) at VO2max. PUFA resulted in a 5.0 (SEM 0.68) mmHg upward shift (P < 0.05) in the PaO2-oxygen uptake relationship, reducing the difference in partial pressure of oxygen between alveolar air and arterial blood (P(A-a)O2) at VO2max [Ctrl 36 (SEM 1.6) vs PUFA 33 (SEM 2.2) mmHg] while PaCO2, remained unchanged. Indomethacin had no effect on either PaO2, ideal partial pressure of oxygen in alveolar gas or P(A-a)O2 in either Ctrl or after PUFA. In contrast, the fall in pH was significantly reduced after indomethacin while VCO2, PaCO2 and lactacidaemia remained unchanged. These observations confirm an effect of PUFA on exercise PaO2 behaviour which does not appear to be mediated by the influence of a series-2 prostaglandin.
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PMID:Effects of indomethacin and polyunsaturated fatty acid diet on exercise-induced hypoxaemia in master athletes. 945 26

The mechanism of the ocular hypotensive effect of bunazosin hydrochloride (an alpha1-adrenergic antagonist) and the possible intermediary role of prostaglandins were studied in New Zealand albino rabbits. Aqueous flow, outflow facility and uveoscleral outflow were determined by fluorophotometry, and intraocular pressure (IOP) was measured by pneumatonometry on the fourth day of twice daily topical treatment with 0.1% bunazosin. Uveoscleral outflow was measured with a tracer infusion technique at 1 to 2 hours after one dose of 0.1% bunazosin. Total outflow facility was measured by a two-level constant-pressure infusion method before and at one hour after one dose of 0.1% bunazosin. The effect of topically applied cyclooxygenase inhibitors, including 0.25% indomethacin and 0.03% flurbiprofen, on the IOP reduction after bunazosin was evaluated. At 3 hours after the seventh consecutive dose given twice-daily, bunazosin significantly (P<0.001) reduced IOP to 13.4+/-0.8 mm Hg (mean +/- SEM) from a baseline of 19.6+/-1.1 mm Hg. Indomethacin significantly inhibited the IOP reduction after one dose of bunazosin, whereas flurbiprofen did not (repeated measures ANOVA). Bunazosin significantly increased uveoscleral outflow (P<0.05) and total outflow facility (P<0.02), but not fluorophotometric outflow facility or aqueous flow. It is concluded that, in rabbits, 0.1% bunazosin reduces IOP predominantly by increasing uveoscleral outflow. The role of prostaglandins in this effect is equivocal.
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PMID:Bunazosin reduces intraocular pressure in rabbits by increasing uveoscleral outflow. 967 29

Prostaglandin E is a major dilator of the fetal ductus arteriosus (DA), but the role of nitric oxide in fetal ductal dilation has not been established. We studied the effects of a potent nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), on the fetal DA in rats. L-NAME was injected into the dorsum of pregnant rats, and fetal DA was studied 4 h later with a rapid whole body freezing method. The inner diameters of the DA and the main pulmonary artery were measured on a freezing microtome. The inner diameter ratio of DA to main pulmonary artery (DA/PA) was 1.02+/-0.03 (mean +/- SEM; number of fetuses [n], 21) in normal near-term fetuses. The effect of prostaglandin synthesis inhibition was studied after orogastric administration of indomethacin to pregnant rats. In near-term rats on the 21st day of gestation (term, 21.5 d), a large dose of L-NAME (100 mg/kg) caused only mild ductal constriction, with DA/PA reduced to 0.83+/-0.05 (n = 20). Indomethacin (1 mg/kg) caused moderate ductal constriction, and DA/PA was decreased to 0.65+/-0.05 (n = 21). Combined administration of L-NAME (10 mg/kg) and indomethacin (1 mg/kg) caused severe ductal constriction, with DA/PA of 0.26+/-0.03 (n = 16). In preterm rats on the 19th day of gestation, a moderate dose of L-NAME (10 mg/kg) caused severe ductal constriction, with a DA/PA of 0.32+/-0.05 (n = 24). Indomethacin (1 mg/kg) alone caused only mild ductal constriction, with DA/PA 0.86+/-0.02 (n = 16). In conclusion, prostaglandin has a major role and nitric oxide has a minor role in dilating the DA in the near-term fetal rat. In contrast, nitric oxide has a major role and prostaglandin has a minor role in dilating the DA in preterm fetal rats.
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PMID:The role of nitric oxide in dilating the fetal ductus arteriosus in rats. 1047 46

It is well established that many cell types produce inflammatory cytokines and we were interested to see whether cells in the neurohypophysis had this ability. This study examines the effect of lipopolysaccharide (LPS) on cytokine production in cultured murine neural lobe (NL) cells. Cells were cultured from the neurohypophysis of mice not older than 5 days and the experiments were performed after 12 days in culture. The majority of cells in culture were immunoreactive for glial fibrillary acidic protein, indicating that the cells were pituicytes. Cytokines were measured in 24-hour samples using commercial ELISA kits. Cells growing in a medium free of endotoxin released 94.3 +/- 6.6 pg IL-6/NL/24 h (mean +/- SEM, n = 21). The release of interleukin-6 (IL-6) was reversible and increased concentration dependently with LPS in the concentration range of 0.1-1 ng/ml. The addition of 1 ng/ml LPS increased the IL-6 release 12-fold to a maximum value of 1,134 +/- 85.5 pg IL-6/NL/24 h (mean +/- SEM, n = 6). No trace of interleukin-1beta (IL-1beta) (<3 pg/NL/24 h) or tumor necrosis factor-alpha (<10 pg/NL/24 h) was detected after LPS stimulation. We examined the effect of dexamethasone (10(-6) M) and indomethacin (10(-4) M) on the release of IL-6 in submaximally stimulated cells. Dexamethasone inhibited the unstimulated and the LPS-stimulated release of IL-6 by 70 and 81%, respectively. Indomethacin had no influence on the release, and it is concluded that cyclooxygenase is not involved in the response. A close association exists between the membrane of the neurosecretory endings and the pituicytes in the neurohypophysis. This naturally raises the question as to whether IL-6 might reflect a physiological connection between the two cell types.
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PMID:Endotoxin-stimulated release of cytokines by cultured cells from the murine neurohypophysis: role of dexamethasone and indomethacin. 1047 51


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