bluuebunny/crossref_metadata_2025_split huggingface dataset:
Curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo and in-vitro
Authors: Kang Hee-Chul , Nan Ji-Xing , Park Pil-Hoon , Kim Ji-Young , Lee Sung Hee , Woo Sun Wook , Zhao Yu-Zhe , Park Eun-Jeon , Sohn Dong Hwan 
Published: October 2002

Abstract
We previously demonstrated that curcumin, a well-known antioxidant, inhibits collagen deposition in carbon tetrachloride-induced liver injury in rats. The major effector cells responsible for collagen synthesis in the liver are activated hepatic stellate cells. In this study, we investigated the inhibitory effects of curcumin on the collagen synthesis and activation of rat hepatic stellate cells in-vitro, and on hepatic stellate cell activation in-vivo. The effects of curcumin on the production of collagen and smooth muscle α-actin proteins and of α1(I) collagen mRNA were studied in-vivo and in-vitro. The effect of curcumin on DNA synthesis was also determined in-vitro. In-vivo, treatment with curcumin reduced collagen deposition and smooth muscle α-actin-positive areas and lowered mRNA levels of type I collagen in the liver. In-vitro, curcumin at a concentration of 5 μg mL−1 reduced DNA synthesis, and downregulated smooth muscle α-actin and type I collagen expression, and α1(I) collagen mRNA expression. We concluded that curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo and in-vitro, and thus may prove a valuable anti-fibrogenic agent.
Synergistic effect of nicorandil and amlodipine on mitochondrial function during isoproterenol-induced myocardial infarction in rats
Authors: Sathish Venkatachalem , Vimal Veereshwarayya , Ebenezar Kesavarao Kumar , Devaki Thiruvengadam 
Published: October 2002

Abstract
The synergistic effects of nicorandil (KATP-channel opener) and amlodipine (calcium-channel blocker) on heart mitochondrial enzymes and the mitochondrial antioxidant defence system was examined on isoproterenol-induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg−1 daily, i.p.) for two days showed significant changes in marker enzymes, mitochondrial enzymes and the mitochondrial defence system. Pre-co-treatment with nicorandil (2.5 mg kg−1 daily, p.o.) and amlodipine (5.0 mg kg−1 daily, p.o.) for 3 days significantly prevented these alterations and restored enzyme activity to near normal. These f ndings demonstrate the protective and synergistic effect of nicorandil and amlodipine in combination against isoproterenol-induced cardiac damage.
α-Adrenergic responsiveness in rat isolated perfused heart after abdominal aortic coarctation
Authors: Silva Cristina O , Duarte Gloria P , Lahlou Saad 
Published: October 2002

Abstract
Chronic isoproterenol pre-treatment, a well-known model of compensatory hypertrophy associated with cardiac β-adrenoceptor desensitization, enhances the inotropic response to phenylephrine in rat isolated perfused hearts, supporting the hypothesis that myocardial α-adrenoceptor stimulation contributes to the maintenance of myocardial performance in situations in which cardiac β-adrenoceptor function is compromised. To further corroborate this hypothesis, the effects of abdominal aortic coarctation on cardiac α-adrenergic responsiveness were investigated in Langendorff heart preparations. Abdominal aortic coarctation causes cardiac hypertrophy (21 %) as shown by a significant increase in the ratio of ventricular dry weight to bodyweight. In preparations from hypertrophied rats, both maximum increases in left ventricular systolic pressure and heart rate elicited by isoproterenol (10−12 to 10−4 M) were significantly reduced (the isoproterenol concentration producing 50% of the maximum positive inotropic and chronotropic responses was enhanced almost 21- and 2-fold, respectively). However, the positive inotropic response to phenylephrine (10−12 to 10−4 M) remained unaffected following abdominal aortic coarctation, when compared with sham-operated rats. In preparations from both groups, phenylephrine infusion did not induce significant changes in heart rate. These results show that although abdominal aortic stenosis induced desensitization of cardiac β-adrenoceptors, it did not enhancecardiac α-adrenoceptor responsiveness. This suggests that such an enhancement depends on the experimental model used to induce cardiac hypertrophy associated with desensitization of cardiac β-adrenoceptors.
Design, synthesis and biological evaluation of novel β-substituted indol-3-yl ethylamido melatoninergic analogues
Authors: Iakovou K , Varvaresou A , Kourounakis A P , Stead K , Sugden D , Tsotinis A 
Published: October 2002

Abstract
A series of new melatonin analogues have been synthesized. Interestingly, two of the new compounds, 11c and 11e, which did not show any appreciable affinity for the melatonin receptor, were found to be potent inhibitors of lipid peroxidation in rat liver microsomes. Analogue 11c, in particular, is a better antioxidant than melatonin.
Vehicles for oligonucleotide delivery to tumours
Authors: Dass Crispin R 
Published: October 2002

Abstract
The vasculature of a tumour provides the most effective route by which neoplastic cells may be reached and eradicated by drugs. The fact that a tumour's vasculature is relatively more permeable than healthy host tissue should enable selective delivery of drugs to tumour tissue. Such delivery is relevant to carrier-mediated delivery of genetic medicine to tumours. This review discusses the potential of delivering therapeutic oligonucleotides (ONs) to tumours using cationic liposomes and cyclodextrins (CyDs), and the major hindrances posed by the tumour itself on such delivery. Cationic liposomes are generally 100–200 nm in diameter, whereas CyDs typically span 1.5 nm across. Cationic liposomes have been used for the introduction of nucleic acids into mammalian cells for more than a decade. CyD molecules are routinely used as agents that engender cholesterol efflux from lipid-laden cells, thus having an efficacious potential in the management of atherosclerosis. A recent trend is to employ these oligosaccharide molecules for delivering nucleic acids in cells both in-vitro and in-vivo. Comparisons are made with other ON delivery agents, such as porphyrin derivatives (&lt; 1 nm), branched chain dendrimers (≈ 10 nm), polyethylenimine polymers (≈ 10 nm), nanoparticles (20–1000 nm) and microspheres (&gt; 1 μm), in the context of delivery to solid tumours. A discourse on how the chemical and physical properties of these carriers may affect the uptake of ONs into cells, particularly in-vivo, forms a major basis of this review.
pH-sensitive, serum-stable and long-circulating liposomes as a new drug delivery system
Authors: Hong Myo-Sook , Lim Soo-Jeong , Oh Yu-Kyoung , Kim Chong-Kook 
Published: October 2002

Abstract
The lack of stability in blood and the short blood circulation time of pH-sensitive liposomes are major drawbacks for their application in-vivo. To develop pH-sensitive, serum-stable and long-circulating liposomes as drug delivery systems, the impact of polyethylene glycol-derived phosphatidylethanolamine (DSPE-PEG) on the properties of pH-sensitive liposomes was investigated. pH-sensitive liposomes were prepared with dioleoylphosphatidylethanolamine (DOPE) and oleic acid (DOPE/oleic acid liposome) or DOPE and 1,2-dipalmitoylsuccinylglycerol (DOPE/DPSG liposome). The inclusion of DSPE-PEG enhanced the serum stability of both DOPE/oleic acid and DOPE/DPSG liposomes, but also shifted the pH-response curve of pH-sensitive liposomesto more acidic regions and reduced the maximum leakage percentage. The impact of DSPE-PEG, however, was much lower in the DOPE/DPSG liposomes than in the DOPE/oleic acid liposomes. In tumourtissue homogenates, where the pH is lower than normal healthytissues, the pH-sensitive DOPE/DPSG liposomes released the entrapped markers rapidly, in comparison with pH-insensitive dipalmitoylphosphatidylcholine/cholesterol/DSPE-PEG liposomes. Moreover, the release rate was not affected by the content of DSPE-PEG. The blood circulation time of methotrexate incorporated in DOPE/DPSG liposomes was significantly prolonged with increasing content of DSPE-PEG. Taken together, the liposomes composed of DOPE, DPSG and DSPE-PEG (up to 5%) were pH sensitive, plasma stable and had a long circulation time in the blood. The complete destabilization of the liposomes at tumour tissues suggests that the liposomes might be useful for the targeted delivery of drugs such as anticancer agents.
Bronchodilator activity of Mikania glomerata Sprengel on human bronchi and guinea-pig trachea
Authors: de Moura R Soares , Costa S S , Jansen J M , Silva C A , Lopes C S , Bernardo-Filho M , da Silva V Nascimento , Criddle D N , Portela B Nunes , Rubenich L M S , Araújo R Gagliardi , Carvalho L C R M 
Published: October 2002

Abstract
The effects of aqueous extracts and hydro-alcoholic extract (HAE), and of a dichloromethane fraction (MG1) obtained from the HAE of Mikania glomerata leaves on isolated respiratory and vascularsmooth muscle have been investigated. Aqueousextracts and HAE induced a significant inhibition on the histamine contractions on the isolated guinea-pig trachea. HAE extract induced a concentration-dependent relaxation on guinea-pig trachea pre-contracted with histamine (IC50 0.34 (0.29-0.39) mg mL−1), acetylcholine (IC50 0.72 (0.67-0.77) mg ml−1) or K+ (IC50 1.41 (1.18-1.64) mg mL−1) and on isolated human bronchi precontracted with K+ (IC50 0.34 (0.26-0.42) mg mL−1). The dichloromethane fraction induced a concentration dependent relaxation in guinea-pig trachea precontracted with K+ (IC50 0.017 (0.012-0.022) mg mL−1). The dichloromethane fraction had also a small vasodilator effect on the isolated mesenteric vascular bed and on the isolated rat aorta, and a significant reduction of the oedema induced by subplantar injections of Bothrops jararaca venom in mice. When tested on plasmid DNA, MG1 did not damage the DNA. Chromatographic analysis showed the presence of 11.4% w/w coumarin in MG1. The results supported the indication of M. glomerata products for the treatment of respiratory diseases where bronchoconstriction is present.
Inhibition of CYP3A-mediated oxidation in human hepatic microsomes by the dietary derived complex phenol, gallic acid
Authors: Stupans Ieva , Tan Hai-Wei , Kirlich Amra , Tuck Kellie , Hayball Peter , Murray Michael 
Published: October 2002

Abstract
Plant polyphenols, such as gallic acid, have been reported to have a range of biological activities including antimutagenic effects. Previously, we reported that gallic acid (3,4,5-trihydroxy-benzoic acid), an agent found in wine and tea, inhibits androstenedione 6β-hydroxylase activity (Ki 70 μM), a cytochrome P450 (CYP3A) marker in human liver microsomes. The preincubation of gallic acid (100 μM) with human liver microsomes in the absence of NADPH, as compared with the presence of NADPH, before assay of androstenedione 6β-hydroxylase activity significantly increased the inhibitory effects of the gallic acid (0.03 ± 0.03 nmol (mg microsomal protein)−1 min−1 compared with 0.20 ± 0.06 nmol (mg microsomal protein)−1 min−1 (P&lt; 0.05)). The antioxidant ascorbic acid and the radical scavenger glutathione prevented this observed increase in inhibition. Removal of gallic acid-derived products from the incubation completely restored CYP3A activity. In contrast, the activities of CYP1A and CYP2E, and non-CYP mediated reductive microsomal 17β-hydroxysteroid dehydrogenase activity were refractory to inhibition by gallic acid.
Identification of indolyl-3-acryloylglycine in the urine of people with autism
Authors: Anderson Rosaleen J , Bendell David J , Garnett Ian , Groundwater Paul W , Lough W John , Mills Malcolm J , Savery Dawn , Shattock Paul E G 
Published: October 2002

Abstract
HPLC analysis of the urine of autistic subjects indicated the presence of an unidentified component in greatly increased concentrations. We have reported the isolation of this component by HPLC and its identification. Mass spectrometry, NMR and UV spectroscopy identified the peak as corresponding to indolyl-3-acryloylglycine (IAG, 3), and this has been confirmed by an independent synthesis.
Gastroprotective activity of solidagenone on experimentally-induced gastric lesions in rats
Authors: Rodríguez Jaime A , Bustamante Carlos , Astudillo Luis , Schmeda-Hirschmann Guillermo 
Published: October 2002

Abstract
The gastroprotective effect of the labdane diterpene solidagenone was assessed on gastric ulcer in rats. The effect of a single oral dose of the compound was evaluated at 50, 100 and 200 mg kg−1 in the following test systems: pylorus ligature (Shay), aspirin- and ethanol-induced gastric ulcers. In pylorus-ligated rats (Shay model), the ulcerative index decreased by 37% with solidagenone pre-treatment at the three assayed doses. The effect of a single oral dose of 50 mg kg−1 solidagenone was comparable with ranitidine at the same concentration and similar to higher doses of the compound. A significant effect (P&lt; 0.001) at 100 and 200 mg kg−1 was observed in the aspirin-induced ulcer model. At both doses, reduction in the number of lesions was approximately 50% compared with controls. The effect was comparable with the reference compound ranitidine (50 mg kg−1). With the ethanol-induced gastric ulcers, the effect of solidagen one at 100 and 200 mg kg−1 was similar to a single oral dose of 20 mg kg−1 omeprazole with a 50% reduction of the mean number of lesions compared with controls. In acute toxicity tests on mice, intraperitoneal administration of solidagenone showed no toxicity at doses up to 600 mg kg−1. This is the first report on the gastroprotective activity of a labdane diterpene.
Simvastatin and lovastatin, but not pravastatin, interact with MDR1
Authors: Sakaeda Toshiyuki , Takara Kohji , Kakumoto Mikio , Ohmoto Nobuko , Nakamura Tsutomu , Iwaki Koichi , Tanigawara Yusuke , Okumura Katsuhiko 
Published: October 2002

Abstract
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, was compared with simvastatin and lovastatin from the viewpoint of susceptibility to interaction with or via the multidrug transporter, MDR1 (P-glycoprotein). This was carried out using the MDR1-overexpressing cell line LLC-GA5-COL150, established by transfection of MDR1 cDNA into porcine kidney epithelial LLC-PK1 cells, and [3H]digoxin, which is a well-documented substrate for MDR1. Pravastatin, at 25–100 μM, had no effect on the transcellular transport of [3H]digoxin whereas simvastatin and lovastatin suppressed the basal-to-apical transport of [3H]digoxin and increased the apical-to-basal transport. It was suggested that recognition by MDR1 was due to the hydrophobicity. In conclusion, simvastatin and lovastatin are susceptible to interaction with or via MDR1, but pravastatin is not. This is important information when selecting the HMG-CoA reductase inhibitors for patients taking drugs that are MDR1 substrates.
Poly(L-lysine) as a model drug macromolecule with which to investigate secondary structure and membrane transport, part I: physicochemical and stability studies
Authors: Chittchang Montakarn , Alur Hemant H , Mitra Ashim K , Johnston Thomas P 
Published: October 2002

Abstract
Low oral bioavailability of therapeutic peptides and proteins generally results from their poor permeability through biological membranes and enzymatic degradation in the gastrointestinal tract. Since different secondary structures exhibit different physicochemical properties such as hydrophobicity, size and shape, changing the secondary structure of a therapeutic polypeptide may be another approach to increasing its membrane permeation. Poly(L-lysine) was used as a model polypeptide. The objectives of this study were to induce secondary structural changes in poly(L-lysine) and to determine the time course over which a given conformer was retained. In addition, the hydrophobicity of each secondary structure of poly(L-lysine) was assessed. The circular dichroism (CD) studies demonstrated that the conditions employed could successfully induce the desired secondary structural changes in poly(L-lysine). The α-helix conformer appeared to be more stable at 25° C whereas the β-sheet conformer could be preserved at 37° C. On the other hand, the random coil conformer was retained at both temperatures. Significant losses of the α-helix and the β-sheet conformers were observed when the pH was reduced. The change in ionic strength did not affect any of the conformers. The octanol/buffer partitioning studies indicated that the α-helix and the β-sheet conformers exhibited significantly different (P&lt; 0.05) hydrophobicities. In conclusion, variation of pH and temperature conditions can be used to induce secondary structural changes in poly(L-lysine). These changes are reversible when the stimuli are removed. The α-helix and the β-sheet conformers of poly(L-lysine) are more lipophilic than the native random coil conformer. Thus, poly(L-lysine) may represent an ideal model polypeptide with which to further investigate the effects of secondary structure on membrane diffusion or permeation.
Stereoselective distribution and stereoconversion of zopiclone enantiomers in plasma and brain tissues in rats
Authors: Fernandez Christine , Alet Patrice , Davrinche Catherine , Adrien Joelle , Thuillier Alain , Farinotti Robert , Gimenez François 
Published: October 2002

Abstract
Concentrations of (-)-zopiclone and (+)-zopiclone were determined in plasma and brain after oral administration, to investigate the stereoselectivity of distribution in rats. Zopiclone enantiomers were administered separately to rats and concentrations were determined by chiral HPLC in plasma and brain. In initial experiments, rats were treated with urethane before cannulation for blood sampling but as this drug modified zopiclone pharmacokinetics, it was not used in subsequent studies. This study showed that zopiclone pharmacokinetics after oral gavage in rats are stereoselective. After oral administration of (+)-zopiclone, no stereoconversion was observed in plasma. Conversely, after administration of (-)-zopiclone, both enantiomers were found in plasma and brain with (+)-zopiclone/(-)-zopiclone ratios of 1 and 8.4 in plasma and brain, respectively. Our findings suggest that zopiclone undergoes stereoconversion and that it is stereospecifically distributed to the brain.
A study of the substrate specificity of Na+-dependent and Na+-independent neutral amino acid transport systems in dog intestinal brush-border membrane vesicles using L-alanine analogues
Authors: Hatanaka Takahiro , Nabuchi Yoshiaki , Ushio Hidetoshi 
Published: October 2002

Abstract
Neutral amino acids are mainly transported across the intestinal brush-border membrane by two Na+-dependent systems (system B0 and system B0,+) and one Na+-independent system (system b0,+). To investigate potential differences in substrate specificity between these systems, we screened ten different alanine analogues for their ability to inhibit the transport of L-alanine in dog intestinal brush-border membrane vesicles. The results suggested that a phenyl group directly attached to the α-carbon has different effects on the Na+-dependent and Na+-independent transport systems, with an increased affinity for the former and a decreased affinity for the latter. Based on these inhibition studies, we investigated [14C] L-phenylglycine transport kinetics in comparison with L-alanine. Similarto L-alanine, L-phenylglycine transport followed at least three routes, however, the km of the Na+-dependent transport system was lower and the k'm of the Na+-independent system was higher than the corresponding values for L-alanine. These results corroborated the conclusions drawn from the inhibition studies. Based on these data, we conclude that different sizes of immediate parts to the α-carbon in functional groups of amino acid analogues have differential effects on the interaction of these amino acid analogues with the Na+-dependent and Na+-independent transport systems for neutral amino acids.
Scutellaria baicalensis inhibits liver fibrosis induced by bile duct ligation or carbon tetrachloride in rats
Authors: Nan Ji-Xing , Park Eun-Jeon , Kim Yoon-Chul , Ko Geonil , Sohn Dong Hwan 
Published: October 2002

Abstract
This study was carried out to investigate the antifibrotic effects of methanol extracts from the traditional Chinese medicinal herb, the root of Scutellaria baicalensis Georgi, on liver fibrosis induced by bile duct ligation and scission (BDL) or carbon tetrachloride (CCl4) in rats. Liver fibrosis was assessed by histological observations and by measuring levels of liver hydroxy-proline, lipid peroxidation based on malondialdehyde (MDA) production, and serum enzyme activities. The morphological characteristics of liver tissue were examined by Masson's trichrome staining and immunostaining against smooth muscle cell α-actin. In both models, the levels of hydroxyproline and MDA in liver were significantly increased. Treatment with a methanol extract of S. baicalensis significantly reduced the levels of liver hydroxyproline and MDA, with improved histological findings. In both models, the liver areas positive for smooth muscle cell α-actin were considerably decreased by treatment with oral methanol extract of S. baicalensis (150 mg kg−1 daily for 28 days). A methanol extract of S. baicalensis root inhibits fibrosis and lipid peroxidation in rat liver induced by BDL or CCl4.
The output of flunisolide from different nebulisers
Authors: O'Callaghan Chris , White Judy , Jackson Judith , Barry Peter , Kantar Ahmad 
Published: October 2002

Abstract
The objective of this study was to determine the output, in-vitro, solution of a concentrated solution of flunisolide from two different nebulisers under simulated breathing conditions. The BimboNeb and Nebula nebulisers were used to nebulise 2.6 mL of flunisolide solution (600 μg). Particle size was determined by inertial impaction and the total output of drug from the nebulisers under simulated breathing conditions was measured using a sinus flow pump. Two different breathing patterns were used, simulating nebuliser use by a child and an adult. The mass median aerodynamic diameter of flunisolide particles from the BimboNeb and Nebula were both 3.9 μm. With the simulated paediatric breathing pattern, both nebulisers delivered similar amounts of flunisolide (56.4 μg (s.d. 1.4μg) and 56.1 μg (5 μg) over 5 min from the BimboNeb and Nebula, respectively). With the adult breathing pattern, flunisolide delivery from the BimboNeb was increased to 88.9 μg (3.3 μg), but delivery from the Nebula was only slightly increased to 64.6 μg (1.4 μg). With both nebulisers, little drug was released after 5 min of nebulisation. Both nebulisers delivered 9–15 % of the nominal dose of flunisolide to the breathing simulator, a similar percentage to previous studies with budesonide and more than previous studies with beclometasone. Drug delivery from the BimboNeb, but not the Nebula, was affected by the simulated breathing pattern. This study suggests that drug delivery from nebulisers is dependent upon the interaction between the nebuliser, the drug and the patient.