bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Gelatin Microparticles to Delay the Release of Readily Water-soluble Materials
Authors: Lou Yan , Groves Michael J 
Published: April 2011

Abstract
The adsorption of D-arabinose onto gelatin microparticles demonstrated a Langmuirian adsorption pattern. Evaluation of the dissolution behaviour of D-arabinose-loaded gelatin microparticles suggested that the saccharide, loaded at a level below the adsorption saturation level, was released uniformly over a 14-h period after the loaded gelatin microparticles had been lyophilized for a second time. When dissolution curves were corrected for the initial burst effect seen after the gelatin microparticles had been loaded at higher levels of D-arabinose and lyophilized, steady-state release rates were also evident over prolonged periods. In addition, it was evident that the D-arabinose was adsorbed onto internal surfaces of the hydrated gelatin matrix. Calculation of this internal surface demonstrated the influence of the concentration of the glutaraldehyde used as a cross-linking agent and this parameter, in turn, influenced both the adsorption maxima and the subsequent equilibrium release rates.
Application of this data base to a highly water-soluble complex polysaccharide antineoplastic agent, which has a higher molecular weight (22·4 kDa vs 150 Da), demonstrated similar behaviour in that a near zero-order release pattern over at least 16 h could be obtained by attention to the conditions under which the gelatin microparticles were made and subsequently loaded before lyophilization.
The Inhibitory Effect of Tannins on Lipid Peroxidation of Rat Heart Mitochondria
Authors: Hong Chuang-Ye , Wang Chein-Ping , Huang Shiang-Suo , Hsu Feng-Lin 
Published: April 2011

Abstract
We induced lipid peroxidation in rat heart mitochondria with ferrous sulphate (FeSO4)) and compared the inhibitory effect of various tannins on the peroxidation.
Oxygen consumption and malondialdehyde (MDA) formation were used to quantitate the amount of lipid peroxidation, and the free radical scavenger activity of tannins was measured with a diphenyl-ρ-picryl hydrazyl (DPPH) method.
Of 25 tannins and related compounds tested, catechin benzylthioether and procyanidin B-2 ben-zylthioether were the most potent in inhibiting lipid peroxidation, with inhibitory effects stronger than that of trolox, a water soluble analogue of vitamin E. The concentrations (IC50) required for catechin benzylthioether and procyanidin B-2 benzylthioether to inhibit oxygen consumption to 50% of control values were 0·85 and 2·0 μm, respectively, while their IC50 values from the inhibition of MDA formation were 0·9 and 1·70 μm, respectively. The IC50 values for catechin and procyanidin B-2 to inhibit oxygen consumption were 34·0 and 11·0 μm. Both compounds were less potent than their benzylthioether derivatives. However, the ability of catechin and procyanidin B-2 to scavenge DPPH were similar to that of their benzylthioether derivatives.
We conclude that conjugation with a benzylthioether group enhances the inhibitory effect of tannins on lipid peroxidation, and that the mechanism is not an increase in its scavenger activity.
Effect of Kil769, a Novel K+-channel Opener, on Sensitivity to Ca2+ of Contractile Elements and Inositol Phosphate Formation in Porcine Coronary Artery
Authors: Yokoyama Takashi , Kasai Hideo , Okada Yuji , Izumi Hideakira , Izawa Toshio , Ogawa Nobuyuki 
Published: April 2011

Abstract
To determine whether Kil769, a novel K+-channel opener, acts intracellularly in vasorelaxation, we compared the effects of Kil 769 on force of contraction, intracellular Ca2+ concentration ([Ca2+]i) and inositol phosphate (IP1) formation with those of Ca2+-channel blockers in isolated porcine coronary artery.
Kil 769 (10 μm) and verapamil (1 μm), which produced submaximal relaxation, reduced the increase in [Ca2+]i and force of contraction induced by 25 mM KC1. Verapamil reduced [Ca2+]i and the force of contraction to a similar extent but Kil 769 reduced force of contraction more strongly than it did [Ca2+]i. Kil 769 also inhibited U46619 (9,11-dideoxy-9α, 11α-methano-epoxy-PGF2a)-induced IP1 formation and glibenclamide blocked its inhibitory effect.
These results suggest that the opening of K+ channels induced by Kil 769 reduces the Ca2+ sensitivity of contractile elements and inositol phospholipid hydrolysis which is related to the Ca2+ release from intracellular storage.
Regulation of Immune Complexes Binding of Macrophages by Pectic Polysaccharide from Bupleurum falcatum L.: Pharmacological Evidence for the Requirement of Intracellular Calcium/Calmodulin on Fc Receptor Up-regulation by Bupleuran 2IIb
Authors: Matsumoto Tsukasa , Yamada Haruki 
Published: April 2011

Abstract
The pectic polysaccharide, bupleuran 2IIb, up-regulates Fc-receptor (FcR) expression on peritoneal macrophages in a dose-dependent manner. The intracellular signal transduction by bupleuran 2IIb leading to the expression of FcR was studied.
Neither the protein kinase C (PKC) inhibitor, 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine dihydrochloride, nor the structurally distinct PKC antagonist, calphostin C, inhibited bupleuran 2IIb-induced up-regulation of FcR, whereas two direct activators of PKC, L-α-l-oleoyl-2-acetyl-sn-3-glycerol and N-(6-phenylhexyl)-5-chloro-l-naphthalenesulphonamide were unable to up-regulate the expression of FcR. The protein kinase A (PKA) inhibitor, N-[2-(methylamino)ethyl]-5-isoquinolinesulphonamide dihydrochloride also did not inhibit bupleuran 2IIb-induced up-regulation of FcR. Fluorescence image analysis using the calcium-sensitive dye, Fura-2, demonstrated that bupleuran 2IIb induced a rapid increase in intracellular levels of calcium (Ca2+). When macrophages were treated with calcium antagonist, 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride, bupleuran 2IIb-induced up-regulation of FcR was inhibited in a dose-dependent manner. The bupleuran 2IIb-induced up-regulation of FcR was also blocked by two structurally distinct calmodulin antagonists, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide hydrochloride. Furthermore, elevation of intracellular Ca2+ using the calcium ionophore, A23187, led to up-regulation of the FcR expression in a dose-dependent manner.
These results suggest that bupleuran 2IIb induces the up-regulation of FcR on macrophages by a mechanism dependent on an increase in intracellular Ca2+ followed by activation of the calmodulin, but not by a PKC or PKA pathway.
Antagonism by SB 204070 of 5-HT-evoked Contractions in the Dog Stomach: an In-vivo Model of 5-HT4 Receptor Function
Authors: Bingham S , King B F , Rushant B , Smith M I , Gaster L , Sanger G J 
Published: April 2011

Abstract
The ability of 5-hydroxytryptamine (5-HT) to evoke contractile activity in the gastric Heidenhain pouch was measured in conscious dogs using a method in which 5-HT4 receptor-antagonist activity can be measured in-vivo.
At doses of 5-HT which evoked short-lived measurable responses (5 or 10 μg kg−1, i.v.), it was found that this activity was greatly reduced by atropine (100 μg kg−1, i.v.), but was unaffected by methysergide, methiothepin, ketanserin (each at 100 μg kg−1, i.v.) or granisetron (10 or 100 μg kg−1, i.v.). At best SDZ 205–557 2-diethylaminoethyl-[2-methoxy-4-amino-5-chloro] benzoate; 100 μg kg−1, i.v.) reduced the action of 5-HT in 4/5 animals and increased it in the other but its effects were variable in magnitude and not consistently maintained. However, the more potent and selective 5-HT4-receptor antagonist SB 204070 (1-butyl-4-piperidinylmethyl 8-amino-7-chloro-1,4-benzodioxan-5-carboxylate hydrochloride) dose-dependently antagonized the 5-HT-evoked contractions in all dogs tested. This action was reversible, but long-lasting with an effective half-life of 18·0 h when administered at 1 μg kg−1. The estimated ID50 value was 0·55 μg kg−1.
Femoral Vasodilation to Cromakalim is Blocked by U37883A, a Non-sulphonylurea that Selectively Inhibits KATP Channels
Authors: Lippton Howard , Choe Ella , Franklin Ernest , Grivas Tania , Flint Lewis , Hyman Albert , Ferrara John 
Published: April 2011

Abstract
The purpose of the present study was to determine the effects of U37883A, a non-sulphonylurea inhibitor of KATP channels, in the femoral vascular bed of the anaesthetized dog.
Administration of U37883A, 4-morpholinecarboxamidine-N-1-adamentyl-N-cyclohexyl hydrochloride (2·5 mg kg−1, i.v.), significantly inhibited the femoral vasodilator response to intra-femoral arterial injection of cromakalim, an activator of KATP channels. In contrast, U37883A had no effect on the femoral vasodilator responses to nitroglycerin, isoprenaline, 5-HT, or 5-carboxamidotryptamine, suggesting this agent is a novel and selective inhibitor of hindlimb vasodilation induced by KATP-channel activation.
Since U37883A did not significantly alter baseline femoral blood flow and femoral vascular resistance, the present data suggest that KATP channels do not contribute, in large measure, to regulating the canine femoral vascular bed under resting conditions in-vivo.
Defibrotide Protects Endothelial Cells, but not L929 Tumour Cells, from Tumour Necrosis Factor-α-mediated Cytotoxicity
Authors: Schröder Henning 
Published: April 2011

Abstract
The effect of defibrotide on the cytotoxicity of tumour necrosis factor-α was investigated in cultured bovine pulmonary artery endothelial cells and L929 mouse tumour cells.
In endothelial cells, a 72-h incubation with tumour necrosis factor-α (1 and 10 ng mL−1) reduced the number of viable cells to 63 and 51% of control, respectively. Simultaneous incubation with defibrotide (0·03-0·3 mg mL−1) protected endothelial cells from tumour necrosis factor-α-mediated cytotoxicity, and increased viability in a concentration-dependent fashion to 98% of control at 1 ng mL−1 tumour necrosis factor-α and to 80% of control at 10 ng mL−1 tumour necrosis factor-α. However, under the same conditions a similar cytotoxic response to tumour necrosis factor-α in L929 tumour cells remained unaltered in the presence of defibrotide.
These findings demonstrate protection from tumour necrosis factor-α-mediated toxicity by defibrotide in endothelial cells but not in a tumour cell line. It is concluded that defibrotide might serve as a therapeutic agent to limit the vascular toxicity of tumour necrosis factor-α without affecting its antineoplastic activity.
Differential Effects of Dopamine Antagonists on Evoked Dopamine Release from Slices of Striatum and Nucleus Accumbens in Rats
Authors: Yamada Shigeto , Takaki Toshihiro , Yokoo Hideyasu , Tanaka Masatoshi 
Published: April 2011

Abstract
The effects of dopamine-receptor antagonists on electrically-evoked dopamine release were compared in the nucleus accumbens and striatal slices of rats.
(-)-Sulpiride induced a concentration-dependent increase in the evoked dopamine release from both regions, the increase in the nucleus accumbens being significantly greater than that in the striatum. Clozapine also increased evoked dopamine release from the nucleus accumbens, but not from the striatum. The haloperidol-induced increase in evoked dopamine release from the nucleus accumbens was less than that from the striatum.
These findings indicate that, in terms of dopamine transmission, (-)-sulpiride and clozapine, but not haloperidol, predominantly affect the nucleus accumbens rather than the striatum. We have previously reported that the contribution of D3 receptors to the regulation of dopamine release from dopamine nerve terminals is much greater in the nucleus accumbens than that in the striatum. (-)-Sulpiride and clozapine have relatively higher affinity for D3 receptors than does haloperidol. The regional differences in responsiveness of dopamine release to dopamine antagonists could be due to the different affinities to D2 or D3 receptors of the dopamine antagonists.
In-vivo Activity of Retinoid Esters in Skin is Related to In-vitro Hydrolysis Rate
Authors: Chen Simon , Darling Inger M , Yu Kuo-Long , Starrett John E , Mansuri Muzammil M , Whiting Gary , Tramposch Kenneth M 
Published: April 2011

Abstract
BMS-181163 (4-acetamidophenyl retinoate, previously reported as BMY-30123), the acetamidophenyl ester of all-trans-retinoic acid (tRA), is topically active in various retinoid-sensitive animal models, but was recently shown to be ineffective for the treatment of acne in patients. To determine whether BMS-181163 functions as a prodrug of tRA in mice but not in man, the relative rates of ester hydrolysis in mouse and human skin homogenates were determined.
In-vitro hydrolysis assays showed that BMS-181163 was substantially hydrolysed in mouse skin homogenates and minimally in human skin preparations. In addition, a series of phenyl esters of tRA and several known active synthetic retinoids (Ch-80: (E)-4-[3-oxo-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl] benzoic acid; CD-271: 6-[3-(1-adamantyl)-4-methyoxyphenyl]-2-naphthoic acid; and TTNPB: (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl] benzoic acid) was prepared and hydrolysis rates and in-vivo (rhino mouse utriculi reduction) activities were compared. The hydrolysis rates of the six test retinoid phenyl esters, ranging from 0·06 to 2·0 h−1 were found to correlate with the in-vivo activity. Those esters (BMS-181163 and acetamidophenyl esters of Ch-80 and TTNPB) with a higher hydrolysis rate exhibited in-vivo activity only slightly lower than their parent free acid retinoids. In contrast, the three phenyl esters with a hydrolysis rate less than 0·3 h−1 were inactive in-vivo.
Data from both approaches suggest that the breakdown of the phenyl ester linkage in this series is essential for the respective in-vivo activity and that the active phenyl esters of retinoids function as prodrugs.
Disposition of Polaprezinc (Zinc l-Carnosine Complex) in Rat Gastrointestinal Tract and Effect of Cimetidine on its Adhesion to Gastric Tissues
Authors: Furuta Shigeru , Toyama Seiji , Miwa Masahiro , Sano Hiroshi 
Published: April 2011

Abstract
The disposition of polaprezinc in the rat gastrointestinal tract was studied by a double tracer method using [14C]- and [65Zn]polaprezinc. At 0·5 h after oral administration of [14C]-, [65Zn]polaprezinc to rats, the 14C-radioactivity in the gastric contents was comparable with the 65Zn-radioactivity. However, a significant difference was observed in the time course of changes in gastric contents between 14C- and 65Zn-radioactivity over 1 h after administration, indicating that polaprezinc existed in complex form at 0·5 h after administration and was dissociated to l-carnosine and zinc in the gastrointestinal tract as a function of time.
The adhesion of zinc to stomach mucosa after oral administration of polaprezinc to rats was significantly increased by treatment with cimetidine.
These results suggest that the adhesion of zinc to gastric tissues is increased by inhibiting the dissociation of polaprezinc, and that H2-receptor antagonists, such as cimetidine, may increase anti-ulcer effects of polaprezinc.
A Novel Metabolite, an Oxepin Formed from Cannabidiol with Guinea-pig Hepatic Microsomes
Authors: Yamamoto I , Nagai K , Watanabe K , Matsunaga T , Yoshimura H 
Published: April 2011

Abstract
The metabolic formation of an oxepin derivative, 3-pentyl-6, 7, 7a, 8, 9, 11a-hexahydro-1, 7-dihydroxy-7, 10-dimethyldibenzo-[b,d]-oxepin, from cannabidiol was studied in-vitro using guinea-pig hepatic microsomes.
The hepatic microsomes catalysed the formation of the metabolite from cannabidiol and 8S, 9-epoxycannabidiol in the presence of an NADPH-generating system and 3, 3, 3-trichloropropene-1, 2-oxide. 8S, 9-Epoxycannabidiol was thought to be an intermediate in the formation of the metabolite, which was identified by gas chromatography-mass spectrometry. The metabolite synthesized from 8S, 9-epoxycannabidiol diacetate exhibited catalepsy, hypothermia and pentobarbitone-induced sleep prolongation in mice, although the pharmacological effect was less potent than that of Δ9-tetrahydrocannabinol.
Different Effects of Traditional Chinese Medicines Containing Similar Herbal Constituents on Prednisolone Pharmacokinetics
Authors: Homma Masato , Oka Kitaro , Ikeshima Ken , Takahashi Noriyuki , Niitsuma Tomoyuki , Fukuda Toshiaki , Itoh Hisao 
Published: April 2011

Abstract
Three major traditional Chinese medicines (TCM), Sho-saiko-To, Saiboku-To, and Sairei-To, consist of similar herbal prescriptions containing glycyrrhizin, which is a strong inhibitor of 11β-hydroxysteroid dehydrogenase. We performed cross-over open trials in healthy subjects to clarify prednisolone pharmacokinetics on co-administration of these preparations.
All subjects received a single oral dose of 10 mg prednisolone before oral treatment with one of the test preparations. After a 2-week wash-out interval, they received one of the test preparations for three days at daily doses of 7·5 or 9·0 g. On the third study day, 10 mg prednisolone was administered orally in combination with the test preparation. Area under the curves (AUC) of prednisolone before and after the treatment decreased from 0·94 to 0·78 mg h L−1 (P &lt; 0·05) in the Sho-saiko-To group, increased from 0·92 to 1.06 mg h L−1 (P &lt; 0·01) in the Saiboku-To group, and did not change in the Sairei-To group. AUC ratios of prednisone and prednisolone, which reflect the 11β-hydroxysteroid dehydrogenase activity, increased in the Sho-saiko-To group (P &lt; 0·01), decreased in the Saiboku-To group (P &lt; 0·01), and did not change in the Sairei-To group after the treatments. Similar results were observed in ratios of endogenous cortisone to cortisol.
Because of the equal glycyrrhizin content in all three preparations, it was unexpected that the 11β-hydroxysteroid dehydrogenase effect was different amongst the three groups. These observations suggest that some unknown metabolic enzyme modifiers, promoters or inhibitors, may be involved in these traditional treatments.
Ophthalmic Preservatives as Absorption Promoters for Ocular Drug Delivery
Authors: Sasaki Hitoshi , Nagano Toshiaki , Yamamura Kenzo , Nishida Koyo , Nakamura Junzo 
Published: April 2011

Abstract
The effects of ophthalmic preservatives on the drug permeability through isolated ocular membranes of albino rabbits were investigated using a two-chamber glass diffusion cell. Tilisolol and fluorescein isothiocyanate (FITC)-dextrans (average molecular weights 4400 and 9400 Da; FD-4 and FD-10, respectively) were used as model penetrants of ophthalmic β-blockers and peptide drugs. Preservatives significantly enhanced the corneal penetration of not only tilisolol but also FITC-dextrans. Especially, benzalkonium chloride increased the corneal permeability of FD-4 and FD-10 by 28·8 and 37·1 times, respectively. These results indicate the usefulness of ophthalmic preservatives as absorption promoters for the ocular delivery of β-blockers and hydrophilic macromolecules. Preservatives also enhanced the conjunctival permeability of tilisolol, FD-4 and FD-10. The promoting effect of preservatives on the conjunctival drug penetration was smaller than that on the corneal one. Preservative increased the ratio of corneal to conjunctival permeability of tilisolol, FD-4 and FD-10.
The different responses of corneal and conjunctival drug penetrations to ophthalmic preservatives may be useful to control the extent and pathway for the ocular and systemic absorptions of instilled drugs.
2-Heteroaryl 2-Substituted Phenylketone Derivatives and Their Inhibitory Activity on Platelet Aggregation
Authors: Hsu Ling-yih , Lee Chyuan-fang , Chou Tz-chong , Ding Yu-an 
Published: April 2011

Abstract
R 68070 and CV-4151 are two compounds possessing both thromboxane synthetase inhibitory activity and thromboxane receptor antagonist properties. 2-Heteroaryl 2-substituted phenylketone derivatives with a partial structural similarity to R 68070 and CV-4151, i.e. possessing a phenyl and a heteroaryl moiety, have been prepared and found to have antiplatelet activity. The compound 2-thienyl 2′-hydroxyphenyl ketone (4) was shown to completely inhibit platelet aggregation induced by arachidonic acid at a concentration of 5·0 μm. Structure-activity analysis indicated that the presence of a ketone group is an important requirement for this inhibitory activity. An o-hydroxyl substitution on the phenyl ring, and a 2-thienyl of heteroaryl ring might increase inhibitory activity.
The Effect of Moisture on the Heckel and Energy Analysis of Hydroxypropylmethylcellulose 2208 (HPMC K4M)
Authors: Nokhodchi Ali , Ford James L , Rowe Philip H , Rubinstein Michael H 
Published: April 2011

Abstract
The influence of moisture content on the Heckel analysis, energy analysis and strain-rate sensivity of hydroxyproplymethylcellulose 2208 (HPMC K4M) has been evaluated.
An increase in moisture content from 0 to 14.9% w/w decreased the mean yield pressure, probably due to a plasticizing effect of moisture which reduced the resistance of particles to deformation. For each moisture content (0, 2.2, 3.8, 5.9, 9.6 and 14.9% w/w), the initial relative density and the extrapolated density from the linear portion of the Heckel plot, tended to decrease with increasing compression speed. Minor changes were observed in the initial relative density due to changes in the moisture content. The strain-rate sensitivity increased from 21.6 to 50.7% as the moisture content increased from 0 to 14.9% w/w, indicating that the plasticity of HPMC increased with increase in moisture content, whereas increase in moisture content from 0 to 14.9% w/w decreased the plastic energy.
Increase in compression force or speed of compaction increased both the plastic and elastic energies. An increase in moisture content from 0 to 5.9% w/w slightly reduced the elastic energy but above 5.9% moisture content the elastic energy was unaffected by the moisture content.
Anti-inflammatory, Analgesic and Ulcerogenic Properties of S-(+)-Ibuproxam, Racemic Ibuproxam-β-cyclodextrin and S-(+)-Ibuproxam-β-cyclodextrin
Authors: Bole-Vunduk Breda , Verhnjak Katarina , Zmitek J 
Published: April 2011

Abstract
The anti-inflammatory, analgesic and gastric mucosal damage-inducing activities of S-(+)-ibuproxam, and S-(+)-ibuproxam-β-cyclodextrin, new propionic acid derivatives, and racemic ibuproxam-β-cyclodextrin were investigated in three animal models and compared with those of racemic ibuproxam, racemic ibuprofen and its optical enantiomer S-(+)-ibuprofen.
The anti-inflammatory activities of racemic ibuprofen, S-(+)-ibuprofen and racemic ibuproxam in carrageenan-induced paw oedema in rats were almost equipotent and slightly greater than those of S-(+)-ibuproxam and S-(+)-ibuproxam-β-cyclodextrin, and significantly greater than that of racemic ibuproxam-β-cyclodextrin. In abdominal constriction tests in mice, the analgesic effects of racemic ibuproxam, S-(+)-ibuproxam, racemic ibuproxam-β-cyclodextrin and S-(+)-ibuproxam-β-cyclodextrin were significantly less pronounced than those of racemic ibuprofen and S-(+)-ibuprofen. Ulcerogenic activity of S-(+)-ibuproxam-β-cyclodextrin in rats was found to be significantly weaker than that of racemic ibuproxam-β-cyclodextrin, racemic ibuproxam and S-(+)-ibuproxam and, most notably, weaker than those of racemic ibuprofen ans S-(+)ibuprofen.
These results indicate that S-(+)-ibuproxam-β-cyclodextrin could be a novel potent anti-inflammatory and analgesic agent with a therapeutic index more favourable than that of the classical non-steroid anti-inflammatory drugs ibuprofen and ibuproxam.