bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanoparticles of 5-fluorouracil (5-FU) loaded N-succinyl-chitosan (Suc-Chi) for cancer chemotherapy: preparation, characterization — in-vitro drug release and anti-tumour activity
Authors: Yan Chengyun , Chen Dawei , Gu Jiwei , Qin Jing 
Published: August 2006

Abstract
N-Succinyl-chitosan has favourable properties as a drug carrier, such as biocompatibility, low toxicity and long-term retention in the body. It is a good candidate for cancer chemotherapy as a polymeric drug carrier. This study describes the preparation and characterization of 5-fluorouracil-loaded N-succinyl-chitosan nanoparticles (5-FU-Suc-Chi/NP) by an emulsification solvent diffusion method. The influence of the initial 5-FU concentration on the nanoparticle characteristics and release behaviour in phosphate-buffered saline solution (PBS) was evaluated. The Suc-Chi nanoparticles had a particle diameter (Z-average) in the range 202∼273 nm and a negative zeta-potential (approx. −27 to −18 mV). The formulation with an initial 5-FU concentration of 1000 μg mL−1 provided the highest loading capacity (19%) and the highest extent of release (61% at 24 h). The 5-FU-Suc-Chi/NP showed good anti-tumour activity against Sarcoma 180 solid tumour and mild toxicity. According to the data obtained, this Suc-Chi-based nanotechnology opens new and interesting perspectives for cancer chemotherapy.
Preparation and evaluation of self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin
Authors: Shen HaiRong , Zhong MingKang 
Published: August 2006

Abstract
Atorvastatin is insoluble in aqueous solution and the bioavailability after oral administration is low. Self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin have been successfully prepared to improve its bioavailability. SMEDDS is a mixture of lipid, surfactant, and cosurfactant, which are emulsified in aqueous medium under gentle digestive motility in the gastrointestinal tract. Pseudo-ternary phase diagrams composed of various excipients were plotted. Droplet size, zeta-potential and long-term physical stability of the formulations were investigated. The release of atorvastatin from SMEDDS capsules was studied using the dialysis bag method in 0.1 m HCl and phosphate buffer (pH 7.4), compared with the release of atorvastatin from a conventional tablet. A pharmacokinetic study was performed in 6 beagle dogs after oral administration of 6 mg kg−1 atorvastatin. The bioavailability of atorvastatin SMEDDS capsules was significantly increased compared with that of the conventional tablet. SMEDDS capsules consisting of Labrafil, propylene glycol and Cremophor RH40 provided the greatest bioavailability. Our studies indicate that the use of SMEDDS for the delivery of atorvastatin can improve its bioavailability.
Effect of plasma lipid on pharmacokinetics of ciclosporin and its relationship with plasma prednisolone level in renal transplant patients
Authors: Sugioka Nobuyuki , Kokuhu Takatoshi , Okamoto Masahiko , Yoshimura Norio , Ito Yukako , Shibata Nobuhito , Takada Kanji 
Published: August 2006

Abstract
Ciclosporin (cyclosporine A, CyA) is a potent immunosuppressant used after organ transplantation. The pharmacokinetic properties of CyA vary widely and lipoproteins are the major complexing constituents for CyA in the plasma. Therefore, a change in lipoprotein level may influence the pharmacokinetic properties of CyA. Prednisolone (PSL) is concomitantly used with CyA as an immunosuppressant. After organ transplantation, hyperlipidaemia resulting from PSL therapy has been mostly observed and PSL increased the plasma lipoprotein level. Therefore, in this study, to obtain more useful information of the therapeutic drug monitoring (TDM) of CyA, the relationship between the plasma PSL level, plasma lipoprotein level and blood CyA level was investigated in detail. An open-label, non-randomized, retrospective study was performed. Data from 21 male and 11 female patients (age 11–65 years) who received a living-related renal transplantation from 2002 to 2004 were included. On postoperative days (PODs) 7, 14 and 28, the area under the plasma concentration-time curve until 9 h after 40 mg of PSL administration (AUCPSL400–9) correlated well with total cholesterol (T-cho) (r = 0.558, 0.768, 0.660, all P &lt; 0.05) and high-density lipoprotein (HDL) (r = 0.688, P &lt; 0.05; 0.835, P &lt; 0.01; 0.508, P &lt; 0.05), and correlated negatively with very-low-density lipoprotein (VLDL) (r = −0.486, P &lt; 0.01; −0.776, P &lt; 0.01; −0.967, P &lt; 0.01). In addition, AUC until 9 h after CyA administration (AUCCyA0–9) also correlated with T-cho (r = 0.797, P &lt; 0.01; 0.577, P &lt; 0.05; 0.901, P &lt; 0.01), HDL (r = 0.514, P &lt; 0.05; 0.614, P &lt; 0.05; 0.893, P &lt; 0.01) and low-density lipoprotein (LDL) (r = 0.906, P &lt; 0.01; 0.573, P &lt; 0.05; 0.537, P &lt; 0.05), and there was a negative correlation with VLDL (r = −0.480, −0.630, −0.632, all P &lt; 0.05). Moreover, AUCCyA0–9 correlated well with AUCPSL400–9 (r = 0.728, P &lt; 0.01; 0.482, P &lt; 0.05; 0.688, P &lt; 0.05); namely, it was considered that the variety of plasma PSL concentrations influenced the pharmacokinetic properties of CyA through the change in lipoprotein levels. These results suggested that monitoring of the biochemical parameters of the plasma lipid and plasma PSL level might be useful for the TDM of CyA.
Site-specific accumulation of the cancer preventive dietary polyphenol ellagic acid in epithelial cells of the aerodigestive tract
Authors: Whitley Alexander C , Sweet Douglas H , Walle Thomas 
Published: August 2006

AbstractEllagic acid (EA), a polyphenol present in berries, has been demonstrated to prevent oesophageal and colon cancer in animals. To better understand the site-specificity of these effects, we studied the accumulation and transport of [14C]EA in rat aerodigestive epithelial cells in-vivo and in cultured human cells. When [14C]EA was administered to rats by gavage, a high content of EA was found in the oesophagus and small intestine at 0.5h after oral administration and in the colon at 12h, with very low amounts in plasma and peripheral tissues. Studies in human intestinal Caco-2 and human oesophageal HET-1A cells found very limited transcellular transport (Caco-2) of EA but high accumulation (Caco-2 and HET-1A) in the cells. In more detailed studies in the Caco-2 cells, accumulation of EA displayed ATP- and Na+-dependency. Multiple interventions permitted the exclusion of a number of transporters as mediators of this uptake. A dramatically reduced transport of EA at low pH (5.5) compared with high pH (7.4) suggested an important role for the negative charge of EA. This was supported by the organic anion transport inhibitors 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid and bromosulfophthalein. The latter produced as much as 78% inhibition at the 100 μm concentration. Finally, Caco-2 cells were shown to express organic anion transporter 4 (OAT4) mRNA, as was the human large intestine. EA appears to be accumulated along the aerodigestive tract using OATlike transporters, one of which might be OAT4.
Plasma profiles of lycopene after single oral and intravenous administrations in dogs
Authors: Vertzoni Maria , Valsami Georgia , Reppas Christos 
Published: August 2006

Abstract
The objectives of this study were to identify the factors limiting the absorption of purified lycopene after oral administration, and to comparatively assess plasma data sets after single oral and intravenous administrations in dogs to define the conditions for performing an absolute bioavailability study. Solubility of purified lycopene (all-trans, 93.5%) was determined in media simulating the conditions in the fasted and in the fed upper gastrointestinal lumen. After evaluating the plasma levels achieved following single administrations of purified lycopene powder to fasted and fed dogs at escalating doses (75–750 mg), a crossover study was performed in four fed female mongrel dogs at two phases. In phase I, one soft gelatine capsule (10 mg lycopene) with 500 mL milk was administered orally. In phase II, 500 mL milk was administered orally and 250 mL 5% dextrose containing 5mg lycopene in the form of a binary system with hydroxypropyl-β-cyclodextrin (HP-β-CyD) was administered intravenously over 3.5 h. In-vitro and preliminary canine studies confirmed that, after oral administration of lycopene in solid form, arrival of lycopene into the systemic circulation was limited by lymphatic transport and, in addition, if the administered dose was higher than approximately 2 mg, by intralumenal solubility. During the first 50 h after single administrations to fed dogs, lycopene plasma levels were lower after intravenous than after oral administration. This could have been related to capacity limited elimination of lycopene and/or route-dependent disposition kinetics. Estimation of the amount of lycopene reaching the systemic circulation after oral and after intravenous administration requires separate estimations of total body clearance of lycopene.
Uptake of dexamethasone incorporated into liposomes by macrophages and foam cells and its inhibitory effect on cellular cholesterol ester accumulation
Authors: Chono Sumio , Morimoto Kazuhiro 
Published: August 2006

Abstract
To confirm the efficacy of dexamethasone incorporated into liposomes in the treatment of atherosclerosis, the uptake of dexamethasone-liposomes by macrophages and foam cells and its inhibitory effect on cellular cholesterol ester accumulation in these cells were investigated in-vitro. Dexamethasone-liposomes were prepared with egg yolk phosphatidylcholine, cholesterol and dicetylphosphate in a lipid molar ratio of 7/2/1 by the hydration method. This was adjusted to three different particle sizes to clarify the influence of particle size on the uptake by the macrophages and foam cells, and the inhibitory effect on cellular cholesterol ester accumulation. The distribution of particle sizes of dexamethasone-liposomes were 518.7 ± 49.5nm (L500), 202.2± 23.1 nm (L200), and 68.6 ± 6.5 nm (L70), respectively. For each size, dexamethasone concentration and dexamethasone/lipid molar ratio in dexamethasone-liposome suspension were 1 mg dexamethasone mL−1 and 0.134 mol dexamethasone mol−1 total lipids, respectively. The zeta potential was approximately −70 mV for all sizes. Dexamethasone-liposomes or free dexamethasone were added to the macrophages in the presence of oxidized low density lipoprotein (oxLDL) and foam cells, and then incubated at 37°C. The uptake amount of dexamethasone by the macrophages and foam cells after a 24-h incubation was L500 &gt; L200 &gt; free dexamethasone &gt; L70. The macrophages in the presence of oxLDL and foam cells were incubated with dexamethasone-liposomes or free dexamethasone for 24 h at 37°C to evaluate the inhibitory effect on the cellular cholesterol ester accumulation. The cellular cholesterol ester level in the macrophages treated with oxLDL was significantly increased compared with that in macrophages without additives. L500, L200 and free dexamethasone significantly inhibited this cholesterol ester accumulation. L500, L200 and free dexamethasone also significantly reduced cellular cholesterol ester accumulation in foam cells. In addition, the relationship between the area under the uptake amount of dexamethasone-time curve (AUC) and the inhibition rate of cholesterol ester accumulation in macrophages and foam cells was evaluated. The inhibition rate of cholesterol ester accumulation (%) was related to the AUC in both types of cell. These results suggested that dexamethasone-liposomes would be a useful approach to the development of a novel drug delivery system for atherosclerotic therapy. Furthermore, the prediction of the inhibitory effect of dexamethasone on cellular cholesterol ester accumulation may become possible by using the results of this study.
Enhanced therapeutic potential of naringenin-phospholipid complex in rats
Authors: Maiti Kuntal , Mukherjee Kakali , Gantait Arunava , Saha Bishnu Pada , Mukherjee Pulok K 
Published: August 2006

Abstract
Naringenin is a naturally occurring flavanone, possessing a variety of biological activity. Due to its rapid elimination, naringenin needs frequent administration to maintain an effective plasma concentration. We have evaluated the therapeutic potential of naringenin-phospholipid complex under oxidative stress conditions compared with free naringenin. Naringenin-phospholipid complex was prepared and assessed for antioxidant activity in carbon tetrachloride intoxicated rats at a dose level of 100 mg kg−1 (p.o.). Liver function tests were studied by assessing serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum alkaline phosphatase and total bilirubin. Marker enzymes of liver, namely glutathione peroxidase, superoxide dismutase, catalase and thiobarbituric acid reactive substances, were measured to evaluate the antioxidant potential at the same dose level. The plasma concentration of naringenin was also measured. It was observed that the naringenin-phospholipid complex enhanced the antioxidant activity of the biomolecule and protected the liver significantly for a longer time as compared with free naringenin at the same dose level. Phospholipid complex of naringenin produced better antioxidant activity than the free compound with a prolonged duration of action, which may be helpful in reducing the fast elimination of the molecule from body.
Voltage-gated Na+ channel ligands and ATP: relative molecular similarity and implications for channel function
Authors: Williams W R 
Published: August 2006

AbstractThe voltage-gated sodium channel (VGNC) is targeted by naturally occurring ligands and drugs of diverse structure. ATP modulates VGNC current in-vitro but is given little prominence in models describing channel function. This computational study uses superimposition and molecular fitting to investigate relative molecular similarity within the structures of ATP and VGNC ligands. A motif of 3 linked atoms (C-N-C) in the adenine ring of ATP satisfies the fitting of a wide range of anticonvulsant structures. An alternative group (N-C-N) provides one fitting motif for the ester and amide groups of local anaesthetic drugs; protonated amine and aromatic groups in the same conformers fit to a second motif in the adenine ring. Analogous structures from other drug classes with VGNC blocking activity give the same molecular fits to ATP. Structures fitted to the adenine ring of ATP occlude the intra-molecular space between the nucleoside and triphosphate chain in approximation to their established blocking, activating or neutral effects on Na+ current. The findings are discussed in terms of drug preferences for VGNC states and channel requirements for ATP.
Indorenate modifies a1-adrenergic and benzodiazepine receptor binding in the rat brain: an autoradiography study
Authors: López-Meraz M L , Neri-Bazán L , Rocha L 
Published: August 2006

AbstractIndorenate (5-methoxytryptamine-β-methylcarboxylate) is a 5-HT1A receptor agonist that produces antihypertensive, anxiolytic, antidepressant and anticonvulsant effects. However, there is evidence suggesting that these effects could involve the activation of benzodiazepine (BZD) receptors but not the activation of a1-adrenergic receptors. The goal of this study was to analyse the effect of indorenate on a1-adrenergic and BZD receptor binding in specific rat brain areas by using in-vitro autoradiography. Coronal brain sections from male Wistar rats were used for labelling 5-HT1A (3H-8-OH-DPAT, 2 nm), a1-adrenergic (3H-prazosin, 2 NM) and BZD (3H-flunitrazepam, 2 NM) receptor binding in the presence or absence of indorenate (1 μm). Indorenate totally displaced 3H-8-OH-DPAT binding in all the brain areas evaluated. It decreased 3H-prazosin binding just in the frontal (30%) and sensorimotor (32%) cortices and in the thalamus (21%). Additionally, indorenate diminished 3H-flunitrazepam binding only in the cingulate (10%) and piriform (18%) cortices as well as in the dorsal raphe nucleus (18%). These results confirm that indorenate is a 5-HT1A ligand and suggest the possible participation of a1-adrenergic and BZD receptors in its pharmacological properties.
Synthesis and pharmacological investigation of novel 1-substituted-4-(4-substituted phenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as a new class of H1-antihistamine agents
Authors: Alagarsamy V , Giridhar Rajani , Yadav M R 
Published: August 2006

Abstract
A series of novel 1-substituted-4-(4-substituted phenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones was synthesized by the cyclization of 2-hydrazino-3-(4-substituted phenyl)-3H-quinazolin-4-one with various one-carbon donors. The starting material, 2-hydrazino-3-(4-substituted phenyl)-3H-quinazolin-4-one, was synthesized from 4-substituted aniline by a novel innovative route. When tested for in-vivo H1-antihistamine activity on conscious guinea-pigs, all the test compounds significantly protected the animals against histamine-induced bronchospasm. The compound 1-methyl-4-(4-chloro phenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (VII) was more potent (72.71% protection), and 1-methyl-4-(4-methoxy phenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (II) was equipotent (71% protection), when compared with the reference standard, chlorpheniramine maleate (71% protection). Compounds II and VII showed negligible sedation (5% and 8% respectively) when compared with chlorpheniramine maleate (25%). Compounds II and VII could serve as prototype molecules for further development as a new class of H1-antihistamines.
Role of four major components in the effect of Si-Ni-San, a traditional Chinese prescription, against contact sensitivity in mice
Authors: Zhang Li , Dong Yi , Sun Yang , Chen Ting , Xu Qiang 
Published: August 2006

Abstract
Previously, we demonstrated the inhibitory effects of Si-Ni-San, a traditional Chinese prescription, on picryl chloride-induced ear contact sensitivity (PCl-CS). This study aimed to evaluate the role of the four major constituents contained in the prescription (saikosaponins, paeoniflorin, naringin and glycyrrhizin) in the inhibitory effect. When administered during the induction phase, saikosaponin a and glycyrrhizin showed significant inhibitory effects, while paeoniflorin and naringin did not. These components in Si-Ni-San also inhibited the activation and proliferation of T lymphocytes as well as the production of cytokines such as tumour necrosis factor-α and interferon-γ to different extents. Saikosaponin a and paeoniflorin dose-dependently reduced the splenocyte adhesion to type I collagen, while glycyrrhizin only showed a slight tendency. Furthermore, treatment with glycyrrhizin or saikosaponin a, rather than paeoniflorin or naringin, moderately inhibited the matrix metalloproteinase (MMP)-2 activity of the splenocytes from PCl-CS mice, and the combination of all four components showed a strong inhibition against MMP-2. Moreover, the components markedly decreased the serum level of nitric oxide in PCl-sensitized mice. The results indicated that saikosaponin a and glycyrrhizin may be the major contributors in the alleviation effect of Si-Ni-San on contact sensitivity, and paeoniflorin and naringin may exhibit a co-operative effect.
Anti-inflammatory, analgesic and anti-oedematous effects of Lafoensia pacari extract and ellagic acid
Authors: Rogerio Alexandre P , Fontanari Caroline , Melo Mirian C C , Ambrosio Sérgio R , de Souza Glória E P , Pereira Paulo S , França Suzelei C , da Costa Fernando B , Albuquerque Deijanira A , Faccioli Lúcia H 
Published: August 2006

Abstract
Lafoensia pacari St. Hil. (Lythraceae) is used in traditional medicine to treat inflammation. Previously, we demonstrated the anti-inflammatory effect that the ethanolic extract of L. pacari has in Toxocara canis infection (a model of systemic eosinophilia). In this study, we tested the antiinflammatory activity of the same L. pacari extract in mice injected intraperitoneally with β-glucan present in fraction 1 (F1) of the Histoplasma capsulatum cell wall (a model of acute eosinophilic inflammation). We also determined the anti-oedematous, analgesic and anti-pyretic effects of L. pacari extract in carrageenan-induced paw oedema, acetic acid writhing and LPS-induced fever, respectively. L. pacari extract significantly inhibited leucocyte recruitment into the peritoneal cavity induced by β-glucan. In addition, the L. pacari extract presented significant analgesic, anti-oedematous and anti-pyretic effects. Bioassay-guided fractionation of the L. pacari extract in the F1 model led us to identify ellagic acid. As did the extract, ellagic acid presented anti-inflammatory, anti-oedematous and analgesic effects. However, ellagic acid had no anti-pyretic effect, suggesting that other compounds present in the plant stem are responsible for this effect. Nevertheless, our results demonstrate potential therapeutic effects of L. pacari extract and ellagic acid, providing new prospects for the development of drugs to treat pain, oedema and inflammation.
Compounds from rose (Rosa rugosa) flowers with human immunodeficiency virus type 1 reverse transcriptase inhibitory activity
Authors: Fu M , Ng T B , Jiang Y , Pi Z F , Liu Z K , Li L , Liu F 
Published: August 2006

Abstract
The aqueous extracts and ethanol precipitates of aqueous extracts of 18 medicinal herbs traditionally used in China were screened for their ability to inhibit human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) in-vitro. Among the samples screened at a concentration of 500 μg mL−1, dried rose (Rosa rugosa) flowers showed the strongest inhibition. The ethanol precipitate of the aqueous extract of R. rugosa was processed and two components (P1 and P2) were obtained after ion exchange chromatography on DEAE-cellulose. Then, P1-a (Mr 150 kDa) and P1-b (Mr 8 kDa) were isolated from P1 by gel filtration on Sephadex G-200. They inhibited the activity of HIV-1 RT with an IC50 of 158 nm and 148.16 μg mL−1 (18.5 μm), respectively. Further structural analyses revealed that P1-a was a polysaccharide-peptide complex, and P1-b was a polymer consisting of acteoside and acteoside derivatives identified by Fourier transform infrared spectroscopy, nuclear magnetic resonance, assays of carbohydrate and protein contents and high-performance liquid chromatography electrospray ionization mass spectrometry.
Cytotoxic activity and cytostatic mechanism of novel 2-arylbenzo[b]furans
Authors: Yang Hua , Pang Ji-Yan , Cai Yu-Chen , Xu Zun-Le , Xian Li-Jian 
Published: August 2006

Abstract
The aims of this study were to screen cytotoxic compounds from 14 newly-synthesized 2-arylbenzo[b]furans and explore their mechanisms of action. Cytotoxicity was determined by the MTT method. Cell-cycle distribution was detected by flow cytometry. Wright-Giemsa staining was performed to demonstrate the morphological features of cells in mitotic phase. Polymerization of tubulin was detected by tubulin assembly assay, and the cellular microtubule network was observed by immunocytochemical study. Among the 14 compounds screened, 4-formyl-2-(4-hydroxy-3-methoxyphenyl)-5-(2-methoxycarbonyethyl)-7-methoxy-benzo[b]furan (ERJT-12) showed significant cytotoxicity. Our results demonstrated that ERJT-12 exhibited anti-cancer activity in a variety of tumour cell lines with an IC50 value (concentration resulting in 50% inhibition of cell growth) of 5.75∼17.29μM. Cell cycle analysis showed a concentration-dependent accumulation of tumour cells in G2/M phase after treatment with ERJT-12. Further investigation indicated that ERJT-12 blocked the cell cycle in M phase, with separation and dispersion of chromosomes. ERJT-12 inhibited tubulin polymerization in-vitro. Changes of the cellular microtubule network caused by ERJT-12 were also detected, which were similar to the changes caused by colchicine. These results suggested that the anti-cancer activity of ERJT-12 is worth further investigation.