Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new indocin research articles will be listed here shortly after becoming available to us.
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Medical research on indocin
J Reprod Med. 2008 Mar; 53(3): 220-2
Catanzarite V, Gambling D, Bird LM, Honold J, Perkins E
BACKGROUND: MgSO4 is widely used for tocolysis. Serious complications are rare as long as dosing is carefully monitored. Adverse effects in muotonic dustrophy have not been previously described. CASE: A 35-year-old woman, gravida 1, para 0, was hospitalized with suspected mild myotonic dystrophy, polyhydramnios and preterm labor at 33 weeks. MgSO4 infusion rapidly resulted in respiratory compromise. Muscular strength returned to baseline after the infusion was stopped. Mother and infant proved to have myotonic dystrophy. CONCLUSION: The choice of tocolytic medication in maternal myotonic dystrophy is problematic. Beta-2 sympathomimetics have been reported to precipitate myotonia. This case illustrates the potential for MgSO4 to cause respiratory embarrassment. Indomethacin may be the tocolytic of choice in myotonic dystrophy.
Developmental changes in endothelium-dependent relaxation of the chicken ductus arteriosus.
J Physiol Pharmacol. 2008 Mar; 59(1): 55-76
Agren P, van der Sterren S, Cogolludo AL, Frazziano G, de Mey JG, Blanco CE, Villamor E
We tested the hypothesis that endothelium-dependent relaxation in the chicken ductus arteriosus (DA) is developmentally regulated. Isolated DA rings from 15-, 19- and 21-day-old (externally pipped) chicken embryos relaxed to acetylcholine (ACh). This relaxation was unaffected by indomethacin but impaired by endothelium removal, by the NO synthase inhibitor L-NAME, and by the soluble guanylate cyclase inhibitor ODQ, suggesting the involvement of NO. This NO production was confirmed with the fluorescent probe DAF-2DA. The combination of apamin and charybdotoxin with L-NAME produced a further inhibition of ACh-induced relaxation, suggesting the participation of a putative EDHF. In the 21-day DA, the relaxations induced by ACh and sodium nitroprusside (SNP) were markedly reduced and scanning electron microscopy demonstrated an irregular endothelial lining with protrusion and detachment of endothelial cells. The relaxations induced by BAY 41-2272 and 8-Br cGMP were not affected by age. When compared with 5%, lower (0%) and higher (21, 95%) O(2) concentrations impaired ACh-induced relaxation. In summary, we found that ACh induces endothelium-dependent relaxation of the chicken DA and that NO and EDHF are involved in this response. During chicken DA closure, endothelial cells undergo morphologic and functional alterations that result in the lack of endothelium-dependent relaxation.
J Ethnopharmacol. 2008 Mar 22;
Song HJ, Shin CY, Oh TY, Sohn UD
Chronic users of non-steroidal anti-inflammatory drugs frequently develop ulcerative lesions in their intestines. The purpose of the present study was to investigate whether eupatilin, an active ingredient derived from Artemisia plants, prevents this side effect in vitro. Extracts of the whole herb of Artemisia asiatica Nakai have been used in oriental medicine for the treatment of inflammation. As measured by the MTT assay, the treatment of cultured feline ileal smooth muscle cells (ISMCs) with 2.5mM indomethacin for 2h decreased the cell viability to 43%. Pretreatment with eupatilin resulted in dose-dependent inhibition on indomethacin-induced cell damage. This cytoprotective effect of eupatilin required concentrations of more than 150muM and incubation periods of longer than 16h. Pretreatment of ISMC with cycloheximide, an inhibitor of protein synthesis, attenuated the cytoprotective effect of eupatilin, suggesting that eupatilin induces proteins that are responsible for the cytoprotection. Heme oxygenase-1 (HO-1), which is known as a cytoprotective enzyme due to its anti-inflammatory actions, is a candidate protein since ZnPP, an HO-1 inhibitor, repressed the protective effect of eupatilin on indomethacin-induced cell damage in a concentration-dependent manner. Western blot analysis revealed that eupatilin-mediated HO-1 induction occurred in a concentration- and time-dependent manner. We also found that PD98059, a MEK (MAPK/ERK kinase) inhibitor, attenuated the eupatilin-induced HO-1 expression and nuclear translocation of transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). Taken together, the data imply that eupatilin protects ISMC from cell damage caused by indomethacin, and that its cytoprotective action could be attributed to eupatilin-mediated HO-1 induction via ERK and Nrf2 signaling in ISMC.
Mechanism of calcium hydroxide-induced neutrophil migration into air-pouch cavity.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Apr 23;
Teixeira de Moraes Costa MM, Penha de Oliveira SH, Gomes-Filho JE
The aim of this study was to investigate cellular migration induced by calcium hydroxide to air-pouch cavities in mice. The migration was more specific to neutrophil and was dose and time dependent (peaking 96 h after stimulation). This migration was inhibited by pretreatment with thalidomide, indomethacin, MK886, meloxicam, dexamethasone, MK886 associated with indomethacin, and MK886 associated with indomethacin and dexamethasone. The air-pouch exudate from animals stimulated with calcium hydroxide showed an increase of leukotriene-B(4) (LTB(4)), interleukin-1beta, tumor necrosis factor alpha (TNF-alpha), cytokine-induced neutrophil chemoattractant (KC), and macrophage inflammatory protein 2 (MIP-2) release. Pretreatment with 3% thioglycollate increased the macrophage population in the air pouch but did not change neutrophil migration. Depleting the resident mast cells through chronic pretreatment with compound 48/80 did not alter neutrophil migration in response to calcium hydroxide. It was possible to conclude that calcium hydroxide-induced neutrophil migration to the air-pouch cavity in mice is mediated by LTB(4), TNF-alpha, KC, MIP-2, and prostaglandins, but it was not dependent on macrophages or mast cells.
Eur J Pediatr Surg. 2008 Apr; 18(2): 103-106
Sönmez K, Karabulut R, Türkyılmaz Z, Demiroğullari B, Ozen IO, Gülen S, Başaklar AC, Kale N
INTRODUCTION: Many factors and mechanisms have been proposed as causes for intussusception (IN); however, the etiology remains unclear. Inflammatory mediators such as tumor necrosis factor (TNF) and interleukin-6 (IL-6), which are elevated during infectious diseases, can significantly affect gastrointestinal motility. Motility changes caused by these agents might contribute to the development of IN. The aim of this experimental study was to determine the preventive effects of indomethacin on lipopolysaccharide (LPS)-induced IN in mice and to investigate the role of TNF and IL-6 on intussusception. MATERIALS AND METHODS: Seventy-eight mice were divided into five groups. In the Control group (n = 6), no procedure was done. In the Sham group (n = 6), 1 ml saline, in the Indomethacin group (n = 6), 10 mg/kg of indomethacin, in the LPS group (n = 30), 12 mg/kg of LPS was administered intraperitoneally (IP). In the Treatment group (n = 30), 10 mg/kg of indomethacin was administered IP following 12 mg/kg of LPS. All animals were laparotomized 6 hours following IP injections. The existence of IN was noted and blood specimens were obtained. TNFalpha and IL-6 plasma level measurements were performed by standard ELISA for mice. The results were compared using the Mann-Whitney U test and one-way ANOVA test. A value of p < 0.05 was considered significant. RESULTS: Five mice (1 in the control, 2 in the LPS, 2 in the Treatment group) were excluded from the study. IN was observed in 6 (20 %) mice in the LPS group, whereas it was not found in any mice in the Treatment group. Mean TNFalpha and IL-6 levels were statistically higher in the LPS group (394.72 +/- 403.79; 195.18 +/- 218.37 pg/ml, respectively) compared to all other groups, including the Treatment group (p < 0.05 for each comparison). Within the LPS group of mice, the levels were higher in animals with IN compared to the mice without IN. CONCLUSION: Increased TNFalpha and IL-6 levels induced by LPS correlated well with the occurrence of IN, and a decrease in these levels via cyclooxygenase (COX) inhibition by indomethacin prevented IN from forming in this experimental model.
Nonaspirin NSAIDs, Cyclooxygenase 2 Inhibitors, and the Risk for Stroke.
Stroke. 2008 Apr 24;
Roumie CL, Mitchel EF, Kaltenbach L, Arbogast PG, Gideon P, Griffin MR
BACKGROUND AND PURPOSE: There is limited information regarding the cerebrovascular safety of cyclooxygenase 2 inhibitors (coxibs) and noncoxib nonsteroidal antiinflammatory drugs (NSAIDs). We determined whether specific NSAIDs, including coxibs, are associated with risk of stroke. METHODS: Retrospective cohort study among Tennessee Medicaid enrollees aged 50 to 84 years between January 1, 1999 and December 31, 2004. Noninstitutionalized persons with continuous enrollment in Medicaid and no stroke or other serious medical illness in the year before cohort entry were included. The 7 most common NSAIDs were examined: celecoxib, rofecoxib, valdecoxib, ibuprofen, naproxen, diclofenac, and indomethacin. Nonuse of NSAIDs was the reference group. Because new use is less susceptible to bias, we conducted a similar analysis confined to new users. The outcome was hospitalization for an incident cerebrovascular event: ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. RESULTS: The cohort included 336 906 persons, with 989 826 person-years of follow-up, and 4354 stroke hospitalizations. There were 4.51 strokes per 1000 person years in the nonuse group, 5.15 strokes per 1000 person years (adjusted HR 1.28, 95% CI 1.06, 1.53) with rofecoxib use, and 5.95 strokes per 1000 person years (adjusted HR 1.41, 95% CI 1.04, 1.91) with valdecoxib use. New use of rofecoxib and valdecoxib led to 6.06 (adjusted HR 1.46 95% CI 1.08, 1.98) and 6.19 (adjusted HR 1.39, 95% CI 0.74, 2.59) strokes per 1000 person years respectively. No other NSAID significantly increased the risk of incident stroke. CONCLUSIONS: Our results indicate an increased risk of stroke with current use of two highly selective coxibs, rofecoxib and valdecoxib, also shown to increase cardiovascular risk. These results also provide some reassurance about other specific NSAIDs regarding stroke risk.
J Neurophysiol. 2008 Apr 24;
Gardam KE, Geiger JE, Hickey CM, Hung AY, Magoski NS
Flufenamic acid (FFA) is a non-steroidal anti-inflammatory agent, commonly used to block non-selective cation channels. We previously reported that FFA potentiated, rather than inhibited, a cation current in Aplysia bag cell neurons. Prompted by this paradoxical result, the present study examined the effects of FFA on membrane currents and intracellular Ca(2+) in cultured bag cell neurons. Under whole-cell voltage-clamp, FFA evoked either outward (Iout) or inward (Iin) currents. Iout had a rapid onset, was inhibited by the K(+) channel blocker, tetraethylammonium, and was associated with both an increase in membrane conductance and a negative shift in the whole-cell current reversal potential. Iin developed more slowly, was inhibited by the cation channel blocker, Gd(3+), and was concomitant with both an increased conductance and positive shift in reversal potential. FFA also enhanced the use-dependent inactivation and caused a positive-shift in the activation curve of the voltage-dependent Ca(2+) current. Furthermore, as measured by ratiometric imaging, FFA produced a rise in intracellular Ca(2+) that persisted in the absence of extracellular Ca(2+), and was reduced by depleting either the endoplasmic reticulum and/or mitochondrial stores. Ca(2+) appeared to be involved in the activation of Iin, as strong intracellular Ca(2+) buffering effectively eliminated Iin, but did not alter Iout. Finally, the effects of FFA were likely not due to block of cyclooxygenase, given that the general cyclooxygenase inhibitor, indomethacin, failed to evoke either current. That FFA influences a number of neuronal properties needs to be taken into consideration when employing it as a cation channel antagonist.
Am J Physiol Gastrointest Liver Physiol. 2008 Apr 24;
Bartoo AC, Nelson MT, Mawe GM
The purpose of this study was to elucidate the mechanisms by which ATP increases guinea pig gallbladder smooth muscle (GBSM) excitability. We evaluated changes in membrane potential and action potential frequency in GBSM using intracellular recording. Application of ATP (100 microM) caused membrane depolarization and a significant increase in AP frequency that were not sensitive to block by tetrodotoxin (0.5 microM). The non-selective P2 antagonist, suramin (100 microM), blocked the excitatory response, resulting in decreased AP frequency in the presence of ATP. The excitatory response to ATP was not altered by PPADS (30 microM), a non-selective P2X antagonist. UTP also caused membrane depolarization and increased AP frequency, with a similar dose-response relationship as ATP. RT-PCR demonstrated that the P2Y4, but not P2Y2, receptor subtype is expressed in guinea pig gallbladder muscularis. ATP induced excitation was blocked by indomethacin (10 microM) and the COX-1 inhibitor, SC-560 (300 nM), but not the COX-2 inhibitor, nimesulide (500 nM). These data suggest that ATP stimulates P2Y4 receptors within the gallbladder muscularis and, in turn, stimulate prostanoid production via COX-1 leading to increased excitability of GBSM. Introduction Key words: biliary motility, COX, purinergic, P2Y, prostaglandins.
AAPS PharmSciTech. 2008 Feb 14;
Karasulu HY, Sanal ZE, Sözer S, Güneri T, Ertan G
The purpose of this research was to develop an emulsion formulation of indomethacin (IND) suitable for nasal delivery. IND was incorporated into the oil phases of oil in water (O/W) and water in oil (W/O) emulsions. For this purpose, different emulsifying agents (Tween 80, Span 80 and Brij 58) were used in two emulsion formulations. When the effects of several synthetic membranes (nylon, cellulose, cellulose nitrate) were compared with the sheep nasal mucosa, the cellulose membrane and sheep nasal mucosa showed similar permeation properties for O/W emulsion (P > 0.05). To examine the absorption characteristics of IND, the anti-inflammatory properties of intravenous solution of IND, intranasal O/W emulsions of IND (with or without enhancers) and intranasal solution of IND (IND-Sol) were investigated in rats with carrageenan-induced paw edema. When citric acid was added to the nasal emulsion, the anti-inflammatory activity was similar to that of intravenous solution (P > 0.05). Finally, it was concluded that, intranasal administration of IND emulsion with citric acid may be considered as an alternative to intravenous and per oral administrations of IND to overcome their adverse effects.
Dig Dis Sci. 2008 Apr 23;
Banerjee D, Bhattacharya S, Bandyopadhyay SK, Chattopadhyay S
Indomethacin caused maximum stomach ulceration in mice on the 3rd day, which was associated with reduction of plasma total antioxidant status (TAS), COX-1, COX-2, mucosal PGE(2), VEGF, and vWF, along with an increase in endostatin levels. Treatment with the phytochemical allylpyrocatechol (5 mg/kg, p.o. for 3 days) provided significant ulcer healing by reversing these biochemical parameters, as well as increasing the EGF expression more than that observed due to ulceration. Omeprazole (3 mg/kg, p.o. for 3 days) provided a similar healing by improving TAS and mucin levels, without significantly altering the other parameters.