Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new feldene research articles will be listed here shortly after becoming available to us.
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Medical research on feldene
J Pharm Sci. 2008 Jun 9;
Zhang X, Wu D, Lai J, Lu Y, Yin Z, Wu W
This work was aimed at investigating the feasibility of fluid-bed coating as a new method to prepare cyclodextrin inclusion complex. The inclusion complex of the model drug piroxicam (PIX) and 2-hydroxypropyl-beta-cyclodextrin (HPCD) in aqueous ethanol solution was sprayed and deposited onto the surface of the pellet substrate upon removal of the solvent. The coating process was fluent with high coating efficiency. Scanning electron microscopy revealed a coarse pellet surface, and a loosely packed coating structure. Significantly enhanced dissolution, over 90% at 5 min, was observed at stoichiometric PIX/HPCD molar ratio (1/1) and at a ratio with excessive HPCD (1/2). Differential scanning calorimetry and powder X-ray diffractometry confirmed absence of crystallinity of PIX at PIX/HPCD molar ratio of 1/1 and 1/2. Fourier transform-infrared spectrometry and Raman spectrometry revealed interaction between PIX and HPCD adding evidence on inclusion of PIX moieties into HPCD cavities. Solid-state (13)C NMR spectrometry indicated possible inclusion of PIX through the pyridine ring. It is concluded that fluid-bed coating has potential to be used as a new technique to prepare cyclodextrin inclusion complex. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.
Blockade of adenosine A(2B) receptors ameliorates murine colitis.
Br J Pharmacol. 2008 Jun 9;
Kolachala VL, Ruble BK, Vijay-Kumar M, Wang L, Mwangi S, Figler HE, Figler RA, Srinivasan S, Gewirtz AT, Linden J, Merlin D, Sitaraman SV
Background and purpose:The adenosine 2B (A(2B)) receptor is the predominant adenosine receptor expressed in the colon. Acting through the A(2B) receptor, adenosine mediates chloride secretion, as well as fibronectin and interleukin (IL)-6 synthesis and secretion in intestinal epithelial cells. A(2B) receptor mRNA and protein expression are increased during human and murine colitis. However, the effect of the A(2B) receptor in the activation of the intestinal inflammatory response is not known. In this study, we examined the effect of A(2B) receptor antagonism on murine colitis.Experimental approach:Dextran sodium sulphate (DSS)-treated mice and piroxicam-treated IL-10(-/-) mice were used as animal models of colitis. The A(2B) receptor-selective antagonist, ATL-801, was given in the diet.Key results:Mice fed ATL-801 along with DSS showed a significantly lower extent and severity of colitis than mice treated with DSS alone, as shown by reduced clinical symptoms, histological scores, IL-6 levels and proliferation indices. The administration of ATL-801 prevented weight loss, suppressed the inflammatory infiltrate into colonic mucosa and decreased epithelial hyperplasia in piroxicam-treated IL-10(-/-) mice. IL-6 and keratinocyte-derived chemokine (KC) concentrations in the supernatants of colonic organ cultures from colitic mice were significantly reduced by ATL-801 administration.Conclusions and implications:Taken together, these data demonstrate that the intestinal epithelial A(2B) receptor is an important mediator of pro-inflammatory responses in the intestine and that A(2B) receptor blockade may be an effective therapeutic strategy to treat inflammatory bowel disease.British Journal of Pharmacology advance online publication, 9 June 2008; doi:10.1038/bjp.2008.227.
Biol Pharm Bull. 2008 Jun; 31(6): 1284-7
Piao MG, Yang CW, Li DX, Kim JO, Jang KY, Yoo BK, Kim JA, Woo JS, Lyoo WS, Han SS, Lee YB, Kim DD, Yong CS, Choi HG
To develop a piroxicam-loaded gelatin microcapsule with enhanced bioavailability, a gelatin microcapsule encapsulated ethanol and piroxicam has been formulated by using gelatin as a water-soluble polymer shell. The aqueous solubility and bioavailability of piroxicam in piroxicam-loaded microcapsule in rats were then evaluated compared to piroxicam powder. The piroxicam-loaded gelatin microcapsule spherical in shape with smooth surface showed the geometric mean diameter of about 19 microm. It had the piroxicam solubility of about 1.87 mg/ml and the amount of ethanol of about 4.37 microg/mg. Furthermore, it gave significantly higher total plasma concentrations, Cmax and area under the blood concentration-time curve (AUC) of piroxicam in rats than did piroxicam powder, indicating that the drug from gelatin microcapsule could be more orally absorbed in rats. In particular, the AUC of piroxicam in gelatin microcapsule was significantly about 2 fold increased compared to piroxicam powder. This enhanced oral relative bioavailability of piroxicam in gelatin microcapsule was contributed by the marked increase in the absorption rate of piroxicam due to the improved solubility of piroxicam. Thus, the piroxicam-loaded gelatin microcapsule developed using spray-drying technique with gelatin, sodium lauryl sulfate and ethanol would be useful to deliver piroxicam in a pattern that allows fast absorption in the initial phase, leading to better absorption.
J Transl Med. 2008; 6: 27
Verdina A, Cardillo I, Nebbioso A, Galati R, Menegozzo S, Altucci L, Sacchi A, Baldi A
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently shown to exert significant anti-tumoral activity in combination with cisplatin (CDDP) on mesothelioma cells. However, the mechanisms through which NSAIDs regulate the cell cycle as well as the signal pathways involved in the growth inhibition, remain unclear. In the present study, using two mesothelioma cell lines, MSTO-211H and NCI-H2452, we have investigated the influence of piroxicam alone and in association with CDDP on proliferation, cell cycle regulation and apoptosis. In both cell lines a significant effect on cell growth inhibition, respect to the control, was observed with all the drugs tested. Moreover, treatment with piroxicam or CDDP alone altered the cell cycle phase distribution as well as the expression of some cell cycle regulatory proteins in both cell lines. These effects were increased, even if in a not completely overlapping manner, after treatment with the association of piroxicam and CDDP. In particular, the two drugs in NCI cell line had a synergistic effect on apoptosis, probably through activation of caspase 8 and caspase 9, while the most evident targets among the cell cycle regulators were cyclin D1 and p21waf1. These results suggest that the association of piroxicam and CDDP specifically triggers cell cycle regulation and apoptosis in different mesothelioma cell lines and may hold promise in the treatment of mesothelioma.
AAPS PharmSciTech. 2008; 9(1): 95-9
Tantishaiyakul V, Permkam P, Suknuntha K
Nitric oxide and prostaglandins in the clenbuterol-induced ACTH and corticosterone secretion.
J Physiol Pharmacol. 2008 Mar; 59(1): 163-75
Gadek-Michalska A, Bugajski AJ, Bugajski J
The present study was designed to determine the involvement of nitric oxide (NO) and prostaglandins (PG) in the stimulatory action of clenbuterol, a selective beta(2)-adrenergic receptor agonist on hypothalamic-pituitary-adrenal (HPA) axis under basal and social crowding stress conditions. Clenbuterol given i.c.v. (10 microg) or i.p. (0.2 mg/kg) considerably increased ACTH and corticosterone secretion. A selective beta(2)-receptor antagonist compound ICI 118551 and non-selective beta-receptor antagonist propranolol given by either route reduced the stimulatory action of clenbuterol. Crowding stress (21 rats in a cage for 7) for 3-7 days significantly reduced the i.c.v. clenbuterol-induced ACTH and corticosterone secretion and i.p. clenbuterol-elicited ACTH secretion. L-NAME, mainly endothelial nitric oxide synthase (NOS) blocker, stronger than L-NNA, a neuronal NOS blocker, reduced the clenbuterol-evoked ACTH and corticosterone secretion in control rats but did not significantly alter this secretion already reduced by crowding stress. Piroxicam, predominantly constitutive cyclooxygenase (COX-1) inhibitor, given i.p. significantly diminished the i.p. clenbuterol-induced ACTH and corticosterone secretion in control rats and tended to reverse the reduction of ACTH secretion by crowding stress. These results indicate that clenbuterol, a selective beta(2)-adrenoceptor agonist, is much stronger stimulator of the HPA axis than isoprenaline, a non-selective beta-receptor agonist. Social crowding stress reduces to a larger extent the HPA response to beta(2)-receptor stimulation. Likewise, in the HPA axis stimulation via beta(2)-adrenoceptors endogenous NO and prostaglandins are significantly involved. Beta2-adrenoceptor is a dominant functional subtype of beta-receptor in the stimulatory and modulatory signals regulating the HPA axis activity under basal and social stress conditions.
Br J Anaesth. 2008 Jun; 100(6): 827-33
Lorenz IH, Egger K, Schubert H, Schnürer C, Tiefenthaler W, Hohlrieder M, Schocke MF, Kremser C, Esterhammer R, Ischebeck A, Moser PL, Kolbitsch C
BACKGROUND: Lornoxicam like other non-steroidal anti-inflammatory drugs (NSAIDs) is widely used for postoperative pain therapy. Evaluation of the effect of lornoxicam on cerebral processing of surgical pain was thus the aim of the present functional magnetic resonance imaging (fMRI) study. METHODS: An fMRI-compatible pain model that mimics surgical pain was used to induce pain rated 4-5 on a visual analogue scale (VAS) at the anterior margin of the right tibia in volunteers (n=22) after i.v. administration of saline (n=11) or lornoxicam (0.1 mg kg(-1)) (n=11). RESULTS: Lornoxicam, which significantly reduced pain sensation [VAS: mean (sd) 4.6 (0.7) vs 1.2 (1.5)], completely suppressed pain-induced activation in the SII/operculum, anterior cingulate cortex, insula, parietal (inferior), prefrontal (inferior, medial), temporal (inferior, medial/superior) lobe, cerebellum, and contralateral (e.g. left-sided) postcentral gyrus (SI). Only the hippocampus and the contralateral superior parietal lobe (BA 7) were activated. CONCLUSIONS: As compared with saline, lornoxicam typically suppressed pain-induced brain activation in all regions except the hippocampus. Furthermore, de novo activation was found in the contralateral, superior parietal lobe (BA 7).
Antiinflammatory and analgesic activity of topical administration of Siegesbeckia pubescens.
Pak J Pharm Sci. 2008 Apr; 21(2): 89-91
Wang J, Cai Y, Wu Y
Several topical formulations containing methanolic extract of Siegesbeckia pubescens was investigated for antiinflammatory and analgesic activities in rat. The effects were studied using carrageenan-induced edema and formalin testing. Piroxicam gel and methyl salicylate ointment were studied as positive control for antiinflammatory and analgesic activity, respectively. The edema inhibition of the preparations containing extract at the doses of 1-5% w/w were significantly different from the control group. The antiinflammatory effect of Siegesbeckia pubescens 4-5% w/w was similar to the effect of piroxicam gel 3 h after carrageenan injection. The analgesic activity of topical preparation with more than 4% w/w was observed in the late phase. The topical analgesic activity of the extract was less than the analgesic activity of methyl salicylate ointment. The results of the present study further confirm the use of Siegesbeckia pubescens traditionally for the treatment of painful inflammatory conditions and can be useful for the treatment of local inflammation.
Nanostructured microspheres produced by supercritical fluid extraction of emulsions.
Biotechnol Bioeng. 2008 Aug 1; 100(5): 1020-33
Della Porta G, Reverchon E
The system poly(lactic-co-glycolic) acid/ piroxicam (PLGA/PX) was selected, as a model system, to evaluate the effectiveness of supercritical carbon dioxide (SC-CO(2)) extraction of the oily phase (ethyl acetate) from oil-in-water emulsions used in the production of polymer/drug microspheres for sustained drug release applications. The influence of process parameters like operating pressure and temperature, flow rate and contacting time between the emulsion and SC-CO(2) was studied with respect to the microsphere size, distribution and solvent residue. Different polymer concentrations in the oily phase were also tested in emulsions formulation to monitor their effects on droplets and microspheres size distribution at fixed mixing conditions. Spherical PLGA microspheres loaded with PX (10% w/w) with mean sizes ranging between 1 and 3 microm and very narrow size distributions were obtained due to the short supercritical processing time (30 min) that prevents the aggregation phenomena typically occurring during conventional solvent evaporation process. A solvent residue smaller than 40 ppm was also obtained at optimized operating conditions. DSC and SEM-EDX analyses confirmed that the produced microparticles are formed by a solid solution of PLGA and PX and that the drug is entrapped in an amorphous state into the polymeric matrix with an encapsulation efficiency in the range of 90-95%. Drug release rate studies showed very uniform drug concentration profiles, without any burst effect, confirming a good dispersion of the drug into the polymer particles.
Lornoxicam protects mouse cornea from UVB-induced damage via inhibition of NF-{kappa}B activation.
Br J Ophthalmol. 2008 Apr; 92(4): 562-8
Yin J, Huang Z, Wu B, Shi Y, Cao C, Lu Y
AIMS: Ultraviolet B (UVB) irradiation activates nuclear factor-kappa B (NF-kappaB) and cyclo-oxygenase (COX). The COX inhibitors are protective against UVB-induced skin damage. The aim of this study is to determine the effect of lornoxicam, a potent COX inhibitor, on UVB-induced corneal damage and its mechanism in a mouse model. METHODS: Eighty female ICR mice were randomly divided into four groups. Corneal damage was graded based on the degree of haze. NF-kappaB activation in the cornea was examined using an electrophoretic mobility shift assay, and tumour necrosis factor (TNF)-alpha production was determined by enzyme-linked immunosorbant assay (ELISA) 6, 24 and 72 h after irradiation. The histopathological changes in cornea were examined under the transmission electronic microscope at 24 h up to 7 days following irradiation. RESULTS: UVB irradiation (1.2 J/cm(2)) induced a significant and sustained increase in the NF-kappaB-DNA binding activity and TNF-alpha production in the cornea, with the peak at 24 h. Apparent stromal oedema and corneal opacity as well as severe histopathological damage including epithelial exfoliation, keratocyte loss and endothelial oedema were observed after irradiation. Treatment with lornoxicam (0.4 mg/kg, intraperitoneal) significantly lowered the grade of corneal opacity and remarkably ameliorated the ultrastructural damage induced by irradiation. Lornoxicam treatment significantly suppressed UVB-induced increases in NF-kappaB-DNA binding and TNF-alpha expression. CONCLUSION: Lornoxicam treatment attenuates UVB-induced corneal damage via inhibition of NF-kappaB activation.