bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of the Compaction Mechanisms of Lactose-based Direct Compression Excipients using Indentation Hardness and Heckel Plots
Authors: Monedero Perales Maria Del Carmen , Muñoz-Ruiz Angel , Antequera Maria Victoria Velasco , Ballesteros Maria Rosa Jiménez-Castellanos 
Published: April 2011

Abstract
Indentation hardness of tablet surfaces has been used to determine the consolidation mechanisms of the lactose-based excipients Fast Flo Lactose, Ludipress, Cellactose and Tablettose. The Leuenberger equation has been modified to obtain values of compressibility and compactability by using a value of compactability obtained from a tablet at maximum applied force and by substituting deformation resistance by relative deformation resistance. Also, parameters obtained from plots of the Heckel tablet-indie and ejected-tablet methods were calculated in order to establish the comparative consolidation mechanisms in the lactose-based excipients under study. The possibility of using the absolute value of the difference between upper and lower surface hardnesses of the tablets made on an eccentric press is suggested as an alternative method to determine the comparative consolidation mechanisms of different substances.
Effect of Hydroxypropyl-β-cyclodextrin on the Antimicrobial Action of Preservatives
Authors: Lehner S J , Müller B W , Seydel J K 
Published: April 2011

Abstract
The interaction between hydroxypropyl-β-cyclodextrin (HP-β-CyD) and several preservatives with different chemical structures was investigated in aqueous solution. Complex stability constants of the 1:1 complexes were calculated from differential spectra. Using the serial dilution test the antimicrobial activities of the preservatives and their complexes against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans were tested and MIC values determined. For highly water-soluble substances like thimerosal and bronopol, low or no inactivation was found; the more lipophilic substances, such as the phenolic compounds, showed strong inactivation when used in combination with HP-β-CyD. The loss in activity by complex formation correlated with the bound fraction, thus suggesting that the appropriate antimicrobial substance for the preservation of cyclodextrin solutions can be selected according to the results of this study.
Protective Effects of Arginine-vasopressin on Aspirin-induced Gastric Mucosal Damage in Anaesthetized Dogs
Authors: Hung Chen-Road , Wang Jiahn-Jyh , Chang Wen-Chang , Shen Ching-Liang 
Published: April 2011

Abstract
The protective effects of graded doses of arginine-vasopressin (AVP) on acidified acetylsalicylic acid (ASA) solution-induced changes in gastric prostaglandin E2 (PGE2) secretion, mucus production, acid back-diffusion and mucosal damage were studied in the bilateral truncal vagotomized stomach of anaesthetized dogs. After 1–4 h intragastric irrigation of the stomach with AVP (1–100 ng kg−1) plus 20 min acidified ASA solution, a significant (P &lt; 0·05) inhibition in gastric mucosal lesions and acid back-diffusion produced by acidified ASA solution was observed. The reduction in the gastric PGE2 secretion and in mucus production provoked by the same dose of acidified ASA solution was also diminished. Furthermore, a correlation (r = 0·883; P &lt; 0·01) between AVP-induced inhibition in ASA-provoked reduction in gastric PGE2 secretion and in mucus production was found. During the experiment, the heart rate, the peripheral arterial blood pressure and the gastric arterial blood pressure were not altered by AVP (1–100 ng kg−1). Thus, intragastric AVP protects gastric mucosa against ASA-induced damage without producing cardiovascular side effects. The inhibitory effects of AVP (100 ng kg−1) on acidified ASA-induced reduction in PGE2 and mucus secretion, as well as on ASA-induced enhancement in acid back-diffusion and erosion production were dose-dependently reversed by a specific V1 antagonist, 1-(β-mercapto-β,β-cyclopentamethylene-propionic acid), 2-(o-methyl)tyrosine-Arg8-vasopressin. From the above results, it is suggested that the protective effects of intragastric AVP on gastric mucosa against acidified ASA-induced damage is at least partly due to stimulation of the biosynthesis of gastric PGE2, which may contribute to the increase in the gastric mucus secretion and to the decrease in acid back-diffusion. Furthermore, the endogenous PGE2 stimulated by AVP may be mediated by V1-receptor activation.
Anti-inflammatory Activity of Polygonum bistorta, Guaiacum officinale and Hamamelis virginiana in Rats
Authors: Duwiejua M , Zeitlin I J , Waterman P G , Gray A I 
Published: April 2011

Abstract
The aqueous ethanolic extracts of Polygonum bistorta L. Polygonaceae, Guaiacum officinale L. Zygophyllaceae and Hamamelis virginiana L. Hamamelidaceae were screened for anti-inflammatory activity. Administered (100 and 200 mg kg−1, p.o.) before the induction of carrageenan rat paw oedema, extracts of P. bistorta significantly suppressed both the maximal oedema response and the total oedema response (monitored as area under the time course curve). H. virginiana was inactive and G. officinale was only active at 200 mg kg−1. At 200 mg kg−1 administered before the induction of adjuvant arthritis, P. bistorta significantly inhibited both the acute and chronic phases of the adjuvant-induced rat paw swelling, while G. officinale and H. virginiana were only active against the chronic phase. Further studies on P. bistorta (100–800 mg kg−1) revealed a dose-dependent inhibition of the carrageenan-induced rat paw oedema over the dose range 100–400 mg kg−1, the E50 value being approximately 158·5 mg kg−1. The extract (200 mg kg−1), administered after the onset of the inflammatory responses reversed the course of both the carrageenan- and adjuvant- induced rat paw swelling. The results confirm that the extracts of P. bistorta, G. officinale and H. virginiana contain anti-inflammatory substances.
Effect of Three Lipophilic Methotrexate Derivatives Upon Mediator Release by Lipopolysaccharide-stimulated Rat Peritoneal Macrophages
Authors: Williams A S , Topley N , Amos N , Williams B D 
Published: April 2011

Abstract
The ability of methotrexate and three lipophilic derivatives (methotrexate-γ-dimyristoylphos-phatidylethanolamine (MγD), methotrexate-α-dimyristoylphosphatidylethanolamine (MαD) and metho-trexate-α-γ-di-dimyristoylphosphatidylethanolamine (MαγD) to modulate mediator release by lipopolysaccharide-stimulated rat peritoneal macrophages was investigated. At nontoxic concentrations, approximately 10 nmol/105 cells, MαD and MγD produced 11·06±1·0 and 75·6 ± 5·2%, respectively, inhibition of tumour necrosis factor (TNF) release (mean ± s.e.m., n = 4). At this same dose MαγD resulted in 68·8 ± 2·1 % inhibition of TNF but cellular ATP levels were reduced by 80%. The inhibitory activity of all three derivatives was dose-dependent. Non-derivatized methotrexate at a concentration of 25 nmol/105 cells had no inhibitory effect upon TNF release (14·7 ±0·8%, n = 3). Determination of prostaglandin E2 (PGE2) levels in the same samples demonstrated that all three conjugates were powerful inhibitors of prostaglandin release. At a quarter of the conjugate concentrations described above the monoamides MαD (31 nmol/105 cells) and MγD (2·5 nmol/105 cells) maintained their effects on PGE2 production with 73±2·3 and 71±2·0% (n=4) inhibition, respectively. At this lower concentration, however, the diamide MαγD (3·1 nmol/105 cells) was less effective in reducing the amount of PGE2 released from the macrophages (29 ± 18%, n = 4). Maximal PGE2 inhibition by each of the conjugates was attained at approximately 5 nmol/105 cells. Unconjugated methotrexate (range of 2·5–20 nmol/105 cells) did not inhibit the release of PGE2 from lipopolysaccharide-stimulated macrophages.
Inhibitory Effects of Daunorubicin on Endothelium-dependent Vasorelaxing Response to Acetylcholine of Rat Aorta
Authors: Wakabayashi Ichiro , Hatake Katsuhiko , Yoshimoto Sachiko , Sakamoto Kunihiro 
Published: April 2011

Abstract
The effect of daunorubicin on the endothelium-dependent vasorelaxing response to acetylcholine was investigated using rat isolated aorta and compared with the effect of aclarubicin. Treatment of aortic strips with daunorubicin (20 μM) significantly attenuated the relaxing response to acetylcholine in the absence of tetraethylammonium, but not in its presence. Pretreatment with daunorubicin at a higher concentration (50 μM) or with aclarubicin (20 μM) strongly attenuated the relaxing response to acetylcholine; this attenuation was unaffected by the presence of tetraethylammonium. The increase in aortic cGMP in response to acetylcholine was also significantly suppressed by pretreatment with 50 μM daunorubicin or 20 μM aclarubicin, but not by treatment with 20 μM daunorubicin. The inhibitory effect of 20 μM aclarubicin on the acetylcholine-induced responses was stronger than that of 50 μM daunorubicin. Even in strips pretreated with both 50 μM daunorubicin and 20 μM aclarubicin, relaxation induced by 0·1 μM sodium nitroprusside was retained. These results suggest that daunorubicin at 20 μM inhibits the endothelium-dependent vasorelaxing response to acetylcholine via a mechanism other than the nitric oxide-mediated pathway, whilst at 50 μM, it inhibits the nitric oxide-mediated vasorelaxation.
Binding Sites of Fluorescent Probes on Human Serum Albumin
Authors: Muller N , Lapicque F , Drelon E , Netter P 
Published: April 2011

Abstract
Human serum albumin is known to have two major and selective drug binding sites, termed sites I and II. The fluorescent probes, dansylamide and dansylsarcosine selectively interact with sites I and II, respectively. However, the binding site of the fluorescent probe dansylglycine on human serum albumin is not clear from the literature. This study investigated whether dansylglycine interacts tightly with site I or II. Spectrofluorimetric titrations (quenching and complex) and circular dichroism measurements were performed to determine the binding characteristics of dansylglycine to human serum albumin. Modification in probe fluorescence was described by fluorescence titrations to be a result of competitive displacement by ligands. The pattern of displacement of this probe by several ligands whose primary binding sites are exactly known, enabled the identification of its specific binding site. The fluorescence of dansylglycine is only extensively changed when ligands of site II are added, suggesting that it strongly interacts with the benzodiazepine/indole binding site on human serum albumin.
Decreased cerebral 5-HT1A receptors during ageing: reversal by Ginkgo biloba extract (EGb 761)
Authors: Huguet François , Drieu Kathy , Piriou Alain 
Published: April 2011

Abstract
Investigation of [3H]8-hydroxy-2(di-n-propylamino)tetralin binding to 5-HT1A receptors in cerebral cortex membranes of Wistar rats showed that the maximal number of binding sites (Bmax) was reduced significantly (22%) in aged (24-month-old) as compared with young (4-month-old) animals. Chronic treatment with Ginkgo biloba extract did not alter binding in young rats but increased binding density significantly (33%) in aged rats. These results confirm previously described age-related 5-hydroxytryptaminergic alterations. Together with data in the literature, they also suggest a restorative effect in aged rats, associated with decreased receptor density resulting from the protective action of Ginkgo biloba extract treatment on neuronal membrane.
Selectivity of LG50643 for Postjunctional Muscarinic-receptor Subtype in the Guinea-pig Trachea
Authors: D’Agostino G , Renzetti A R , Zonta F , Subissi A 
Published: April 2011

Abstract
The effects of (±)-LG50643, a new N-quaternary tropinic ester of phenylcyclohexene carboxylic acid, endowed with a potent antimuscarinic activity, have been investigated on muscarinic receptor-mediated responses of the guinea-pig trachea to electrical field stimulation. An isolated preparation which allows the simultaneous measurement of tritiated acetylcholine release (prejunctional effect) and smooth muscle contraction (postjunctional effect) was used. The guinea-pig epithelium-deprived trachea was stimulated with 500 pulses (20 Hz, 1 ms, 9 V for 5 s, 30 s apart) in the presence of indomethacin (1 μm). Three successive pre- and postjunctional responses were observed. The potencies (– logEC50) of (±)-LG50643 for pre- and postjunctional muscarinic receptors were determined and compared with those of selective muscarinic antagonists. In addition, the affinity values of (±)-LG50643 for muscarinic-receptor subtypes were determined in radioligand binding experiments in cerebral cortex, heart and salivary glands of rat as target tissues for M1, M2 and M3 receptors, respectively. The results obtained in both functional and binding assays indicate (±)-LG50643 is a potent and selective antagonist for the M3-receptor subtype.
The effect of (—)-4-(2-hydroxy-3(N-isopropylamino)-propoxyimino)-cis-carane on basal and forskolin-stimulated accumulation of cyclic AMP in the cerebral cortical slices of the rat
Authors: Librowski Tadeusz , Nalepa Irena , Czarnecki Ryszard , Vetulani Jerzy 
Published: April 2011

Abstract
(–)-4-(2-Hydroxy-3(N-isopropylamino)-propoxyimino)-cis-carane, a local anaesthetic and platelet aggregation inhibitor which is much more potent than lignocaine, facilitated forskolin-induced cyclic (c) AMP accumulation in cerebral cortical slices of the rat. Lignocaine was ineffective in this respect. It is hypothesized that a cAMP-related mechanism may be involved in increased efficacy of the compound.
Selective effects of pentamidine on cytosolic and granule-associated enzyme release from zymosan-activated human neutrophilic granulocytes
Authors: Arnott M A , Bennett N D , Cairns D , Hay J 
Published: April 2011

Abstract
Therapeutic concentrations (0·3–1·5 mg L−1) of pentamidine isethionate, normally obtainable in-vivo after parenteral administration of the drug, did not affect the in-vitro activity of the enzymes lysozyme, β-glucuronidase or myeloperoxidase released from zymosan-activated human neutrophilic granulocytes. At concentrations of 0·7, 1·1 and 1·5 mg L−1, activity of cytosolic enzymes lactate dehydrogenase and glucose-6-phosphate dehydrogenase were reduced relative to untreated cells (P&lt; 0·001 and P &lt; 0·01, respectively), but not in a dose-dependent fashion. Cell viability, as determined by dye-exclusion remained unaffected.
The Influence of Surface Properties on Uptake of Oil into Complex Coacervate Microcapsules
Authors: Rabiskova M , Song J , Opawale F O , BURGESS D J 
Published: April 2011

Abstract
A range of surfactants with different hydrophile-lipophile balance (HLB) values was selected to investigate the influence of interfacial properties on the uptake of oil droplets into complex coacervate microcapsules. The well characterized gelatin/acacia complex coacervate system was used in this study and the encapsulation of squalane, and oleic acid was investigated. The surfactants investigated were Span 85, Span 80, Span 40, egg yolk lecithin, and Tween 80. Combinations of surfactants were utilized to obtain intermediate HLB values. The percentage oil encapsulated was determined gravimetrically, based on the initial concentration and the amount extracted from the microcapsules. The aqueous interfacial tension values of the oils and oil/surfactant systems were measured using the Wilhelmy plate method. The interfacial properties were correlated to the percentage oil uptake by the coacervate phase. The relative hydrophobicity/lipophilicity of the oil influenced its uptake by complex coacervate droplets. The presence of surfactant affected oil uptake, depending on the HLB value of the surfactant or surfactant mixture. Uptake of squalane by the gelatin/acacia coacervates was found to be optimized by the addition of surfactants with HLB values in the range 2·5–6. The percentage uptake of oil decreased rapidly for systems prepared containing surfactants with HLB values outside this range. No correlation was observed between oil uptake by the coacervate phase and the interfacial tension of the oil and oil/surfactant systems with double-distilled deionized water.
Investigating the Surface Properties and Bioadhesion of Buccal Patches
Authors: Guo Jian-Hwa 
Published: April 2011

Abstract
By using a two-roll milling method, a new bioadhesive polymer patch formulation for drug controlled delivery and consisting of Carbopol 934P (CP), polyisobutylene (PIB), and polyisoprene (PIP) was prepared. The effects of different ratios of CP:PIB:PIP on the surface properties, adhesion, and swelling of buccal patches were investigated. It was found that the surface properties of buccal patches were not only dependent on the CP content but also dependent on the PIB:PIP ratio. The strongest peeling strength was found on the buccal patches with a CP:PIB:PIP ratio of 50: 43·75: 6·25. The maximum bioadhesion of patches was found following 2- to 8-h contact with the test medium, and this observation could be explained by the interpenetration of macromolecular chains at the polymer-polymer interface (based on the diffusion theory of polymer adhesion).
Pharmacokinetic Characteristics of 5-Fluorouracil and Mitomycin C in Intraperitoneal Chemotherapy
Authors: Kuzuya Takafumi , Yamauchi Masaji , Ito Akihiro , Hasegawa Masaya , Hasegawa Takaaki , Nabeshima Toshitaka 
Published: April 2011

Abstract
Eight patients with malignancies confined to the peritoneal space participated in this study. Five hundred milligrams 5-fluorouracil or 10 mg mitomycin C was diluted in 1 L saline. The mixed solution was injected intraperitoneally through the semi-permanent peritoneal catheter. Blood and peritoneal fluid were collected after injection. 5-Fluorouracil concentrations in the peritoneal fluid were 1000 times those in serum, while mitomycin C concentrations were 100 times those in serum. Areas under the concentration vs time curve (AUC) were calculated by the trapezoidal method with extrapolation to infinity. The ratio of peritoneal fluid AUC to serum AUC was about 1400 for 5-fluorouracil and 80 for mitomycin C. Patterns for the absorption and elimination from systemic circulation were similar for both compounds. Drug concentrations in the peritoneal fluid and serum were analysed according to the compartment model. The half-life in the peritoneal fluid (t½p) and the rate constant from the peritoneal fluid to the systemic circulation (ka) were nearly equal for both 5-fluorouracil and mitomycin C (t½p, 1·0 h for 5-fluorouracil and 1·3 h for mitomycin C; ka 0·71 h−1 for 5-fluorouracil and 0·68 h−1 for mitomycin C), although the apparent volume of distribution (Vds/F) and clearance in the peritoneal cavity (CLp) for mitomycin C (78 Lm−2 and 1.8 L h−1 m−2) were about twice the values for 5-fluorouracil (149 L m−2 and 0·8 L h−1 m−2).
Separation and Quantification of Murein and Precursors from Enterobacter cloacae after Treatment with Trimethoprim and Sulphadiazine
Authors: Richards R Michael E , Xing Dorothy K L 
Published: April 2011

Abstract
The intracellular concentrations of the soluble murein precursors UDP-Mur-NAc-pentapeptide in the cytoplasm, the membrane-bound lipid precursor disaccharide pentapeptide and the muropeptides of Enterobacter cloacae cultures treated with trimethoprim (12·5μg mL−1) and sulphadiazine (250 μg mL−1) were determined by using capillary zone electrophoresis analysis. In the presence of trimethoprim, UDP-Mur-NAc-pentapeptide as well as disaccharide pentapeptide accumulated. In the case of sulphadiazine-treated cells, the concentration of UDP-Mur-NAc-pentapeptide roughly paralleled the control cells but sulphadiazine caused a slow incremental accumulation of disaccharide pentapeptide. The muropeptide composition of the murein indicated that the differences between the peptidoglycans produced by the control cells and the cells grown in the presence of either trimethoprim or sulphadiazine alone or in combination were quite marked. The results suggest that the enhanced activity of trimethoprim plus sulphadiazine against E. cloacae is caused by an additional effect on the inhibition of the bacterial peptidoglycan biosynthesis and that this additional effect is a fundamental part of the antibacterial action of the antimetabolites. This effect leads to changes of cell morphology and resultant changes in bacterial cell permeability.
Use of the Walden Product to Evaluate the Effect of Amino Acids on Water Structure
Authors: Lutz Olivier , Vrachopoulou Maria , Groves Michael J 
Published: April 2011

Abstract
The Walden Product, the product of viscosity (η0) and conductivity at infinite dilution of a solution (Λ0), provides a measurement of the water-structuring activity of the solute. Measuring the effect of concentration on viscosity of solutions of amino acids, together with the conductivity of solutions of sodium chloride containing increasing concentrations of the amino acids, enabled Walden Products to be determined. The classical form of the Walden Product (Λ0η0) was used, together with a modified form, Λ0ηc, in which ηc was the slope of the concentration/viscosity curve. Most amino acids demonstrated modest water-structure-breaking activity but l-lysine, l-glutamic acid and l-aspartic acid, and their respective salts, all showed relatively higher activity. Dextrose behaved as a classical water-structure maker and, when added progressively, reversed the breaking activity of l-lysine. It is speculated that effects seen in bulk water may also occur at emulsion droplet surfaces, thereby inducing structural changes associated with the occasional rapid instability experienced when making admixtures of phospholipid-stabilized emulsions and additives such as amino acids and dextrose.
A Study of Modified Betaines as Cryoprotective Additives
Authors: Lloyd Andrew W , Olliff Cedric J , Rutt Ken J 
Published: April 2011

Abstract
Glycinebetaine and N-modified betaines have been previously shown to be effective at reducing leakage from liposomes on freeze-thaw procedures. This study involved the preparation of a series of other modified betaines and the comparison of their abilities to reduce leakage from frozen multilamellar liposomes. All the compounds investigated, with the exception of the octyl ester of betaine, reduced the degree of leakage on freezing and thawing with additive concentrations up to 0·6 m. The betaine esters were less effective than betaine as cryoprotective additives and caused an increase in the leakage from unfrozen liposomes. Taurinebetaine, a sulphobetaine, was also less effective at reducing leakage on freezing than betaine and again increased leakage from unfrozen liposomes. Increasing the number of methylene groups between the carboxylate group and the nitrogen improved the ability to reduce leakage, particularly at lower additive concentrations.
Peracylated β-Cyclodextrins as Novel Sustained-release Carriers for a Water-soluble Drug, Molsidomine
Authors: Uekama Kaneto , Horikawa Takashi , Yamanaka Masayuki , Hirayama Fumitoshi 
Published: April 2011

Abstract
Peracylated β-cyclodextrins with different alkyl chains (acetyl-octanoyl) were prepared by acylating all hydroxyl groups of β-cyclodextrin (β-CyD), and their physical properties were evaluated. These hydrophobic β-CyDs decreased the release rate of molsidomine, a peripheral vasodilator, in proportion to the lengthening of alkyl chain and suppressed a peak plasma level of molsidomine following oral administration of peracylated β-CyD complexes to dogs. Among the peracylated β-CyDs tested, perbutanoyl-β-CyD maintained sufficient plasma drug levels for a long period of time, while other peracylated β-CyDs having shorter or longer chains were inappropriate to control the in-vivo release behaviour of molsidomine. The prominent retarding effect of perbutanoyl-β-CyD was ascribable to the appropriate mucoadhesive property and hydrophobicity, compared with other peracylated β-CyDs. The present results suggest that perbutanoyl-β-CyD is particularly useful in modifying the release rate of water-soluble drugs as a novel slow-release carrier.