Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new indomethacin research articles will be listed here shortly after becoming available to us.
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Medical research on indomethacin
J Obstet Gynaecol. 2008 Jul; 28(5): 485-489
Gedeon C, Anger G, Lubetsky A, Miller MP, Koren G
Glyburide, a drug used to treat gestational diabetes has previously been shown not to be measurable in fetal blood, and to be transferred from the fetal to the maternal circulation against a concentration gradient. The objective of the study is to determine whether indomethacin, an inhibitor of the multi-drug resistance family (MRP) of transporters is involved in the active efflux of glyburide from the fetus to the mother. Using the dually perfused human placental cotyledon model, 12 perfusions were performed of both glyburide and indomethacin concomitantly. The rate of transfer of glyburide in the presence of inhibitor was not different from the rate of transfer of glyburide in the absence of inhibitor. Furthermore, our study suggests that MRP1, 2 or 3 may be only minimally involved in the transport of glyburide across the human placenta. These results pose other ABC transporters, such as likely candidates for the placental transfer of glyburide.
Life Sci. 2008 Sep 24;
Milano J, Rossato MF, Oliveira SM, Drewes C, Machado P, Beck P, Zanatta N, Martins MA, Mello CF, Rubin MA, Ferreira J, Bonacorso HG
AIMS AND MAIN METHODS: The aim of the present study was to evaluate the antinociceptive effect of the novel pyrazoline methyl ester: 4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF4) in two models of pain: arthritic pain caused by Complete Freund's Adjuvant (CFA) and postoperative pain caused by surgical incision in mice. KEY FINDINGS: MPF4 given intraperitoneally (1.0 mmol/kg, i.p.) produced marked antinociception in inflammatory allodynia caused by CFA. The antinociceptive effect produced by MPF4 was reversed with the pre-treatment of animals with naloxone or naltrindole. Oral administration of MPF4 (1.0 mmol/kg, p.o), dipyrone (1.0 mmol/kg, p.o.) and morphine (0.026 mmol/kg, p.o.) also produced an anti-allodynic effect. However, none of the compounds evaluated reversed the paw edema produced by CFA. Moreover, MPF4, dipyrone and morphine also produced an anti-allodynic effect in the surgical incisional pain model. The maximal inhibitions obtained with preemptive drug treatment were 66+/-7%, 73+/-9% and 88+/-8% for MPF4 (1.0 mmol/kg, p.o.), dipyrone (1.0 mmol/kg, p.o.) and morphine (0.026 mmol/kg, p.o.), respectively. The maximal inhibitions obtained with curative drug treatment were 53+/-9%, 83+/-7% and 84+/-7%, for MPF4, dipyrone and morphine, respectively. Unlike indomethacin, MPF4 did not induce gastric lesions at the dose that caused the highest antinociception (1.0 mmol/kg, p.o). The anti-allodynic action of MPF4, dipyrone and morphine was not associated with impairment of motor activity. SIGNIFICANCE: The results of the present study suggest that MPF4 represents a potential target for the development of new drugs to treat persistent inflammatory pain.
Indomethacin and retinopathy of prematurity: The hidden paradox.
J Pediatr. 2008 Oct; 153(4): 587-588
Hammerman C
Effect of amphotericin B lipid complex (ABLC) in very low birth weight infants.
Pediatr Nephrol. 2008 Oct 10;
Auron A, Auron-Gomez M, Raina R, Viswanathan S, Mhanna MJ
The aim of this retrospective, case-control study was to determine the effect of the amphotericin B lipid complex (ABLC) on serum creatinine (SCr), blood urea nitrogen (BUN), sodium (Na), and potassium (K) in very low birth weight (VLBW) infants. Medical records of all VLBW infants who were admitted to our Neonatal Intensive Care Unit between May 1998 and May 2006 and had received ABLC for at least 2 weeks were reviewed for patient demographics, use of medications (ABLC, diuretics, xanthines, indomethacin, vancomycin, gentamicin, pressors, and inotropes), fluid intake, urinary output, and serum electrolytes. Thirty-five patients who received ABLC were identified and matched by gestational age (GA) to 35 patients who served as controls. Infants who received ABLC had an average GA of 25.7 +/- 2.1 weeks and a birth weight of 764 +/- 196 g. Between day 1 and 14 of ABLC treatment, the BUN decreased from 17.5 +/- 11.5 to 10.5 +/- 6.8 mg/dl (p = 0.01), the SCr varied between 0.78 +/- 0.32 and 0.69 +/- 0.32 mg/dl, Na varied between 136.6 +/- 5.8 and 137.8 +/- 3.6 mEq/l, and K varied between 4.8 +/- 0.9 and 4.9 +/- 0.6 mEq/l, respectively. Based on these results, we conclude that treatment with ABLC for 2 weeks did not increase BUN or SCr, nor decrease Na or K in VLBW infants.
Toxicon. 2008 Sep 20;
Pessini AC, Kanashiro A, Malvar DD, Machado RR, Soares DM, Figueiredo MJ, Kalapothakis E, Souza GE
The present study investigated the role of kinins, prostaglandins (PGs) and nitric oxide (NO) in mechanical hypernociception, spontaneous nociception and paw oedema after intraplantar (ipl) injection of Tityus serrulatus venom (Tsv) in male Wistar rats. Tsv was ipl-injected in doses of 0.01-10mug/paw. Pre-treatment (30min prior) with DALBK (100nmol/paw) and icatibant (10nmol/paw), B1 and B2 selective kinin receptor antagonists, l-NAME (50mg/kg, i.p., a non-selective nitric oxide synthase inhibitor) or celecoxib, selective COX-2 inhibitor, was given 1h prior per os (5mg/kg, p.o.), significantly reduced the hypernociceptive response (Von Frey method), the spontaneous nociception (determined by counting the number of flinches) and paw oedema (plethysmometer method) induced by Tsv at doses of 1.0 and 10& mu;g/paw for both nociceptive and oedematogenic responses, respectively. Nevertheless, indomethacin (5mg/kg, i.p., 30min prior) was ineffective in altering all of these events. The results of the present study show that Tsv, injected ipl into the rat paw, causes a dose-dependent paw oedema, mechanical hypernociception and flinches (a characteristic biphasic response) in which kinins and NO are substantially involved. Although celecoxib was effective against the oedema and pain caused by Tsv, COX-2 does not seem to be involved in the inflammatory response caused by Tsv.
Am J Physiol Regul Integr Comp Physiol. 2008 Oct 8;
Bivol LM, Hultstrom M, Gudbrandsen OA, Berge RK, Iversen BM
The effect of tetradecylthioacetic acid (TTA) on the cyclooxygenase (COX) system was investigated in 2K1C hypertensive rats. The systolic blood pressure (BP) was increased 6 weeks after clipping to 183 +/- 4 mmHg vs.127 +/- 3 mmHg in TTA treated 2K1C rats. The COX1 protein expression was not affected either by the 2K1C procedure or by TTA treatment. COX2 expression was up-regulated in both kidneys, but to a greater extent in the clipped kidney. COX2 activity was 16+/-3% in control and 38 +/-2% (p
Hepatobiliary Pancreat Dis Int. 2008 Oct; 7(5): 503-8
Xu J, Cao H, Liu H, Wu ZY
BACKGROUND: Nitric oxide (NO) and prostacyclin (PGI2) are both powerful vasoactive substances correlated with the hyperhemodynamics of portal hypertension (PHT), a common syndrome characterized by a pathological increase in portal venous pressure. The purpose of the present study was to evaluate the possible interaction between these two endothelial vasodilators, together with their respective roles in the hyperdynamic splanchnic circulation of PHT. METHODS: Ninety-six male Sprague-Dawley rats were randomly divided into three groups: intrahepatic portal hypertension (IHPH) induced by injection of CCl4 (n=31), prehepatic portal hypertension (PHPH) induced by partial stenosis of the portal vein (n=33), and sham-operated controls (SO) (n=32). Animals of each group received indomethacin (INDO), a cyclooxygenase (COX) inhibitor, either short-term (7 days) or long-term (15 days), with saline as control. Free portal pressure (FPP), together with the concentration of NO and PGI2 in serum were measured. The activity of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) in the abdominal aorta and small intestine were determined by spectrophotometry. RT-PCR was performed to measure the levels of cNOS and iNOS mRNA in the arteries and small intestines. RESULTS: Compared with SO rats, the concentrations of NO and PGI2 in PHT rats were elevated, which were consistent with the increased FPP (P
J Agric Food Chem. 2008 Oct 9;
Yun KJ, Koh DJ, Kim SH, Park SJ, Ryu JH, Kim DG, Lee JY, Lee KT
To investigate the anti-inflammatory potential of sinapic acid as well as the underlying mechanism involved, we studied the inhibitory effect of sinapic acid on the production of pro-inflammatory mediators in vitro and then evaluated its in vivo anti-inflammatory effect. Sinapic acid inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E 2 (PGE 2), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta production in a dose-dependent manner. Consistent with these findings, sinapic acid inhibited LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygase (COX)-2 at the protein levels, and iNOS, COX-2, TNF-alpha, and IL-1beta mRNA expression in RAW 264.7 macrophages, as determined by Western blotting and reverse-transcribed polymerase chain reaction, respectively. Sinapic acid suppressed the LPS-induced activation of nuclear factor-kappaB (NF-kappaB), a transcription factor pivotal necessary for pro-inflammatory mediators, such as iNOS, COX-2, TNF-alpha, and IL-1beta. This effect was accompanied by a parallel reduction of the nuclear translocation of p65 and p50 NF-kappaB subunits, as well as IkappaB-alpha degradation and phosphorylation. The effects of sinapic acid on acute phase inflammation were investigated on serotonin- and carrageenan-induced paw edema and compared with indomethacin (10 mg/kg, p.o.) or ibuprofen (100 mg/kg, p.o.). Maximum inhibitions of 34.2 and 44.5% were observed at a concentration of 30 mg/kg for serotonin- and carrageenan-induced paw edema, respectively. These results suggest that the suppressions of the expressions of iNOS, COX-2, TNF-alpha, and IL-1beta via NF-kappaB inactivation are responsible for the anti-inflammatory effects of sinapic acid.
Zhongguo Zhong Yao Za Zhi. 2008 Jul; 33(14): 1720-3
Zhang TX, Niu CQ, Hu JM, Liu H, Jing HE
OBJECTIVE: To study the vasodilation effect of the procyanidin (PC) extracted from grape seeds on rabbit thoracic aortic rings in vitro, decreasing blood pressure in vivo and the possible mechanism. METHOD: Rabbits aortic rings were isolated and were divided into six groups including removal of endothelium, integrity of endothelium, 1 x 10(-5) mol X L(-1) indomethacin (Indo), 1 x 10(-5) mol x L(-1) propranolol (Prop), 1 x 10(-4) mol x L(-1) N(omega)-nitro-L-arginine (L-NNA) and 1 x 10(-5) mol x L(-1) methylene blue (MB). Then the thoracic aortic rings were treated with PC with cumulative concentrations of 1.25, 2.5, 5.0 mg x L(-1) respectively and the changes of tension were recorded, and investigate the effect of 40 mg x L(-1) PC on the contraction of aortic smooth muscles, thoracic aortic rings were pre-treated with NA (1 x 10(-8) to approximately 1 x 10(-5) mol x L(-1)), KCl (6.3 to approximately 100 mmol x L(-1)) and CaCl2 (1 x 10(-5) to approximately 1 x 10(-5) mol x L(-1)) followed by treatment with PC. Then, rabbits common carotid artery was intubated and arterial blood pressure in vivo was recorded. PC with cumulative concentrations of 4.0, 8.0, 16, 32, 64, 84 mg x kg(-1) was injected into vein and the changes of arterial blood pressure were observed. RESULT: PC could relax isolated rabbit aorta and showedan obvious concentration-dependent relaxation (r = 0. 63, P < 0.001). The relaxant effect of PC was significantly reduced by removal of endothelium and by treatment with nitric oxide synthase inhibitor L-NNA, or guanylyl cyclase inhibitor MB. In addition PC could decrease the dose response curves of aortic rings to NA, KCl and CaCl2. PC has a significant concentration-dependent negative effect on arterial blood pressure in vivo (r = 0.92, P < 0.001). CONCLUSION: PC has a vasodilation effect not only in an endothelium-dependent, nitric oxide involved manner, but in inhibition of calcium release and blockage of potential-dependent calcium channels. PC could decrease the rabbit's arterial blood pressure significantly in vivo.
Relaxant effects of flavonoids on the mouse isolated stomach: Structure-activity relationships.
Eur J Pharmacol. 2008 Sep 27;
Amira S, Rotondo A, Mule F
Flavonoids are a large heterogeneous group of benzo-gamma-pyrone derivatives, which are abundantly present in our diet. In this study we investigated the effects of six flavonoids (apigenin, genistein, quercetin, rutin, naringenin and catechin) on the gastric tone in mouse isolated stomach. The mechanical activity was recorded as changes of intraluminal pressure. All flavonoids tested produced a concentration-dependent relaxation, which was reversible after washout. The relative order of potency of the flavonoids was apigenin>/=genistein>quercetin>naringenin>/=rutin>catechin. Analysis of the chemical structure showed that the relaxant activity was progressively diminished by the presence of hydroxyl group at C-3, saturation of the C-2, C-3 double bound, saturation of the C-2, C-3 double bound coupled with lack of the C-4 carbonyl and glycosylation. The flavonoid-induced relaxations were not modified in the presence of tetrodotoxin, a voltage-dependent Na(+)-channel blocker, N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, indomethacin, an inhibitor of cycloxygenase or tetraethylammonium, a non-selective blocker of potassium channels. In conclusion, this study provides the first experimental evidence for gastric relaxant activity of flavonoids. This action is influenced to a great extent by the structure of the molecules and it seems not to be dependent on neural action potentials, NO/prostaglandin production or activation of K(+) channels.