bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Assessment of D-Xylose Absorption between Small Intestine and Large Intestine
Authors: Yuasa Hiroaki , Kuno Chiaki , Watanabe Jun 
Published: April 2011

Abstract
The present study aimed to evaluate the absorption of D-xylose, a passively absorbed five-carbon monosaccharide, from the large intestine compared with the small intestine, in order to explore the absorption potential of the large intestine.
D-Xylose absorption was evaluated in the intestinal loop and everted sacs in rats and comparisons were made between small intestine (mid-gut) and large intestine (colon). The absorption of D-xylose was smaller, by an order of magnitude or more, after administration into the loop of large intestine than after administration into that of small intestine, based on appearance in plasma and disappearance from the intestinal loop. D-Xylose absorption was practically insignificant (nominal 4.9%) in 60 min in the large intestine, whereas it was moderate (57.0%) in the small intestine. Consistently, the uptake of D-xylose in everted sacs was about 20 times larger in the small intestine than in the large intestine.
Thus the passive membrane permeability of D-xylose was demonstrated to be negligible in the large intestine, even though the small intestine was fairly permeable. This result helps rationalize kinetic modelling strategies assuming the small intestine as the sole absorption site for gastrointestinal absorption in-vivo. It also suggests that hydrophilic drugs with molecular size similar to or larger than D-xylose may not be good candidates for colonic drug delivery by controlled release.
In-vitro Permeability of the Human Nail and of a Keratin Membrane from Bovine Hooves: Influence of the Partition Coefficient Octanol/Water and the Water Solubility of Drugs on their Permeability and Maximum Flux
Authors: Mertin Dirk , Lippold Bernhard C 
Published: April 2011

Abstract
Penetration of homologous nicotinic acid esters through the human nail and a keratin membrane from bovine hooves was investigated by modified Franz diffusion cells in-vitro to study the transport mechanism.
The partition coefficient octanol/water PCOct/w of the esters was over the range 7 to &gt; 51000. The permeability coefficient P of the nail plate as well as the hoof membrane did not increase with increasing partition coefficient or lipophilicity of the penetrating substance. This indicates that both barriers behave like hydrophilic gel membranes rather than lipophilic partition membranes as in the case of the stratum corneum. Penetration studies with the model compounds paracetamol and phenacetin showed that the maximum flux was first a function of the drug solubility in water or in the swollen keratin matrix. Dissociation hindered the diffusion of benzoic acid and pyridine through the hoof membrane. Since keratin, a protein with an isoelectric point of about 5, is also charged, this reduction can be attributed to an exclusion of the dissociating substance due to the Donnan equilibrium. Nevertheless, the simultaneous enhancement of the water solubility makes a distinct increase of the maximum flux possible.
In order to screen drugs for potential topical application to the nail plate, attention has to be paid mainly to the water solubility of the compound. The bovine hoof membrane may serve as an appropriate model for the nail.
Effect of Tamoxifen on the Pharmacokinetics of Theophylline in Rats
Authors: Poisson Denise , Dupuis Antoine , Breteau Michel , Bouquet Serge , Poterre Marc , Couet William 
Published: April 2011

Abstract
The effect of tamoxifen on the pharmacokinetics of theophylline was investigated in male Sprague–Dawley rats.
The oral administration of tamoxifen at a dose equal to 40 mg kg−1 48 h before the intravenous injection of theophylline 10 mg kg−1, significantly (P &lt; 005) increased the clearance of theophylline by 39%, with no apparent effect on the volume of distribution. As a consequence, the elimination half-life of theophylline was significantly (P &lt; 005) shortened in the tamoxifen-treated rats (3.56 ± 0.39 h vs 5.25 ± 0.48 h) as well as its mean residence time (5.04 ± 0.60 h vs 7.50 ± 0.75 h). Although these data cannot be directly extrapolated to the clinical situation, they provide experimental support to suggest that more attention should be paid to the potential risk of pharmacokinetic interactions in the presence of tamoxifen.
Intestinal Safety of Water-soluble β-Cyclodextrins in Paediatric Oral Solutions of Spironolactone: Effects on Human Intestinal Epithelial Caco-2 Cells
Authors: Tötterman Ann M , Schipper Nicolaas G M , Thompson Diane O , Mannermaa J-P 
Published: April 2011

Abstract
Effects of water-soluble β-cyclodextrins (βCDs) on intestinal epithelial integrity were investigated, to establish the safe use of these βSCDs as solubilizers of spironolactone in paediatric enteral solutions. Mannitol permeability and transepithelial resistance (TER) of human intestinal epithelial Caco-2 cell monolayers during exposure to dimethyl-β-cyclodextrin (DMβCD), hydroxypropyl-β-cyclodextrin (HPβCD) and sulphobutyl ether β-cyclodextrin (SBEβCD) were followed. Staining methods were used to discern cells with damaged membranes and to study the integrity of cytoskeletal actin and tight junctions. Cytotoxicity of the βCDs was tested by effects on intracellular dehydrogenase activity.
Exposure to HPβSCD and SBEβCD solutions had only minor effects on the integrity of Caco-2 cell monolayers. In contrast, DMβCD clearly increased the epithelial permeability for the hydrophilic marker [14C]mannitol across Caco-2 monolayers, decreased TER and showed a dose-dependent cytotoxicity. According to staining, DMβCD increased the permeability of the apical cell membrane without discernable effects on cytoskeletal actin.
HPβCD and SBEβCD appear to be safe additives for use in enteral spironolactone preparations with respect to their acute local effects on epithelial integrity.
Modifications on Antioxidant Capacity and Lipid Peroxidation in Mice under Fraxetin Treatment
Authors: Martín-Aragón Sagrario , Benedí Juana M , Villar Angel M 
Published: April 2011

Abstract
Fraxetin belongs to an extensive group of natural phenolic antioxidants. We have investigated the modifications in endogenous antioxidant capacity; superoxide dismutase (SOD), catalase (CAT), total and selenium-dependent glutathione peroxidases (GPx) and glutathione reductase (GR) and stress index; glutathione disulphide (GSSG)/reduced glutathione (GSH) ratio and thiobarbituric acid-reactive substances (TBARs) in liver and brain supernatants of C57BL/6J male 12-month-old mice under fraxetin treatment for 30 days.
Liver SOD and GPx (total and Se-dependent) activities were not significantly affected by fraxetin, whereas they were increased in the brain compared with control animals. GR activity increased significantly only in the liver of treated mice. Fraxetin treatment-related decreases were shown for GSSG/GSH ratio and rate of accumulation of TBARs (not significant in TBARs) in both tissues.
We concluded that the net effect of fraxetin treatment on endogenous antioxidant capacity suggests that this compound might provide an important resistance to, or protection against, free-radical-mediated events which contribute to degenerative diseases of ageing.
Studies on the Inhibitory Effects of Analogues of Dapsone on Neutrophil Function In-vitro
Authors: Coleman Michael D , Smith Joanna K , Perris Alan D , Buck Nicola S , Seydel Joachim K 
Published: April 2011

Abstract
We have compared twelve sulphone analogues of dapsone in terms of inhibition both of zymosan-mediated human neutrophil respiratory burst and inhibition of interleukin-1-stimulated neutrophil adhesion to transformed human umbilical vein endothelial cells.
Overall, there was a good correlation between the respective rank orders of compound potency in the two test systems. The most effective compounds in terms of respiratory burst and adherence inhibition were the 2-nitro-4-amino-, 2-hydroxy-4-aminopropyl-, and 2-methoxy-4-aminoethyl- derivatives. In general, potency was inversely associated with lipophilicity; compounds with bulky side-chains, e.g. the 2-methyl-4-aminopentyl, 2-methyl-4-aminohexyl and the 2-hydroxymethyl-4-aminoethyl derivatives, were less potent. A 2-hydroxy-4-amino- derivative was the exception, however, with low lipophilicity and relatively low potency.
All of the compounds tested showed comparable or greater inhibition in both the neutrophil-mediated assays compared with dapsone. Some of the compounds might, because of their good tissue penetration and lower toxicity than dapsone, have the potential to undergo further development.
VB20B7, a Novel 5-HT-ergic Agent with Gastrokinetic Activity. I. Interaction with 5-HT3 and 5-HT4 Receptors
Authors: Ramirez M J , García-Garayoa E , Romero G , Monge A , Roca J , Del Río J , Lasheras B 
Published: April 2011

Abstract
This study describes the in-vitro interaction of the gastrokinetic agent 2[1-(4-piperonyl)piperazinyl]benzothiazole (VB20B7) with the 5-hydroxytryptamine 5-HT3 and 5-HT4 receptor subtypes, using functional as well as radioligand binding studies. The benzamide derivative cisapride was used as a comparison.
In radioligand binding assays VB20B7 showed, like cisapride, a weak affinity at 5-HT3 receptors from rat cerebral cortex. The new compound lacked any affinity at other 5-HT receptors or at dopaminergic D2 receptors, whereas cisapride showed high affinity for the 5-HT4 receptors from guinea-pig hippocampus and moderate affinity at dopaminergic D2 receptors. In the non-stimulated guinea-pig ileum, the concentration-response curves to the specific 5-HT3 agonist 2-Me-5-HT and to 5-HT were shifted to the right by VB20B7. In the rat oesophagus tunica muscularis mucosae preparation (TMM), VB20B7 was evaluated for its activity at 5-HT4 receptors. VB20B7 behaved as a 5-HT4 receptor agonist, inducing a concentration-dependent relaxation of the preparation precontracted with carbachol. In this preparation, VB20B7 and cisapride were able to stimulate adenylate cyclase activity, an effect probably mediated through activation of 5-HT4 receptors, as can be inferred from the blockade by the 5-HT4 antagonist, tropisetron, of the enhanced cAMP formation. However, consistent with the lack of affinity at central 5-HT4 receptors, VB20B7 did not stimulate cAMP formation in guinea-pig hippocampal slices. VB20B7 also caused an increase in the twitch response of the transmurally stimulated guinea-pig ileum, although at a concentration higher than cisapride. This effect was blocked by desensitization of the 5-HT4 receptor with 5-MeOT and also by the 5-HT4 receptor antagonist tropisetron. Both VB20B7 and cisapride increased the K+-evoked acetylcholine release in this preparation.
The results show that VB20B7 possesses affinity for 5-HT4 receptors located in the rat TMM and guinea-pig ileum preparations, but is devoid of affinity at central 5-HT4 receptors. In addition, VB20B7 shows low to moderate affinity at both central and peripheral (enteric) 5-HT3 receptors The interaction of VB20B7 with the peripheral 5-HT4 and 5-HT3 receptors may be relevant for the gastrokinetic effects of the new compound.
Endothelium-dependent Vascular Responses in 1,3-Dipropyl-8-sulphophenylxanthine (DPSPX) Hypertensive Rats
Authors: Paiva M Q , Santos M J , Albino-Teixeira A 
Published: April 2011

Abstract
The study was undertaken to test the endothelium-mediated vascular responses in rats rendered hypertensive by chronic administration of 1,3-dipropyl-8-sulphophenylxanthine (DPSPX). The relaxant effect of carbachol (an endothelium-dependent relaxing drug) and of sodium nitroprusside (an endothelium-independent relaxing drug) as well as the potentiation of the contractile effect of noradrenaline by NG-nitro-l-arginine methyl ester (l-NAME) were compared in aortic rings from normotensive and DPSPX-hypertensive rats.
Carbachol and sodium nitroprusside caused concentration-dependent relaxations in aortic rings precontracted by 1 μM noradrenaline. The relaxant effect of carbachol was significantly reduced in tissues of DPSPX-hypertensive rats: the maximal relaxant effect being 86 ± 3% and 64 ± 4% (of the pre-existing tone) in normal and hypertensive rats, respectively, while there were no significant differences in the relaxant effect of sodium nitroprusside. l-NAME (100 μM) significantly reduced the EC50 values of noradrenaline (3.71 ± 0.28 times, n = 8 and 2.96 ± 0.27 times, n = 7, in normal and hypertensive rats, respectively) and significantly enhanced the maximal contractile effect of noradrenaline (46 ± 8%, n = 8 and 35 ± 6%, n = 7, in normal and hypertensive rats respectively): the factors of reduction of EC50 values and the percentages of enhancement of the maximal contractile effect in the aorta of normal and hypertensive rats were not significantly different.
The results obtained provide evidence of functional impairment of the endothelium in DPSPX-hypertensive rats.
Interaction of Thrombin-activated Platelets with Extracellular Matrices (Fibronectin and Vitronectin): Comparison of the Activity of Arg-Gly-Asp-containing Venom Peptides and Monoclonal Antibodies Against Glycoprotein IIb/IIIa Complex
Authors: Sheu J R , Ko W C , Hung W C , Peng H C , Huang T F 
Published: April 2011

Abstract
Platelets adhere to fibronectin and vitronectin substrates following activation with physiological concentrations of thrombin. Adhesion of activated-platelets to either substrate is dependent upon the amount of fibronectin and vitronectin, and the duration of the adhesion assay. In this study, we showed that the Arg-Gly-Asp-containing peptides (including naturally occurring polypeptides, triflavin, trigramin and rhodostomin, synthetic peptides GRGDS, GRGDSPK, GRGDF, and GRGD and monoclonal antibodies, 7E3, 10E5 and AP2, raised against glycoprotein IIb/IIIa complex, inhibited the adhesion of activated-platelets to fibronectin and vitronectin-coated plates in a dose-dependent manner.
In fibronectin-coated plates, GRGDF was shown to be much more efficient than GRGDS, GRGDSPK and GRGD at inhibiting the adhesion of activated-platelets to immobilized fibronectin. On the other hand, there were no marked differences in the abilities of these three peptides (GRGDF, GRGDS and GRGDSPK) to inhibit platelet adhesion to immobilized vitronectin. Furthermore, the RGD-containing venom peptide, triflavin was more effective than rhodostomin and trigramin at inhibiting the adhesion of activated-platelets to either substrates. The monoclonal antibodies raised against glycoprotein IIb/IIIa complex (i.e., 7E3, 10E5 and AP2) inhibited platelet adhesion to fibronectin and vitronectin in a similar dose-dependent manner. Interestingly, we found that 7E3 was more efficient than 10E5 and AP2 in this reaction.
These studies suggest that the glycoprotein IIb/IIIa complex, present on activated-platelets, may interact with fibronectin and vitronectin substrates through the Arg-Gly-Asp-dependent mechanism. Since fibronectin and vitronectin are present in the subendothelial matrix, they may be involved in platelet-vessel wall interaction. The Arg-Gly-Asp containing peptide, especially triflavin, is an ideal therapeutic agent for inhibiting thrombus formation by interrupting platelet-platelet and platelet-subendothelium interactions.
Reversible Blockade of Retrograde Axonal Transport in the Rat Sciatic Nerve by Vincristine
Authors: MacFarlane B V , Wright A , Benson H A E 
Published: April 2011

Abstract
Altered axoplasmic transport has been implicated as a contributing factor in neuropathic pain states. Treatments which produce transient axoplasmic transport blockade have shown initial promise as therapeutic procedures in the management of chronic neuropathic pain. The present study evaluated the capacity of the vinca alkaloid, vincristine to produce reversible blockade of retrograde axoplasic transport.
Results indicated that intraneural administration of 10−5 M vincristine resulted in blockade of retrograde axoplasmic transport of [3H]leucine 24 h following administration. Importantly, the effect reversed over the next four days and axoplasmic transport was re-instated fully at day five.
The implications of these results are discussed in relation to the potential use of axoplasmic transport blocking agents in the management of chronic neuropathic pain.
Effect of Cationic Surfactant on Transport of Model Drugs in Emulsion Systems
Authors: Yoon Kyung Ae , Burgess Diane J 
Published: April 2011

Abstract
Excess surfactant present in emulsions can influence the rates of transport of incorporated drugs by micellar solubilization, alteration of the partitioning process and by drug-surfactant complexation. Cetyltrimethylammonium bromide (CTAB), a cationic surfactant was selected to investigate these phenomena as it forms relatively stable mineral oil–water (O–W) emulsions and has the potential for ionic interaction. Phenylazoaniline, benzocaine, benzoic acid and phenol were chosen as model drugs for this study.
The emulsion critical micelle concentration (CMC) for CTAB determined using a combination of a membrane equilibrium technique and surface-tension measurement was 10% w/v in 10% v/v% O-W emulsion systems. Ionic interaction between model drugs and surfactants and drug hydrophobicity affected their transport rates in the emulsion systems. The transport rates of the lipophilic drugs (benzocaine and phenylazoaniline) and the ionized hydrophillic drug (benzoic acid, pH 70) in the emulsion systems increased with increasing CTAB concentration up to 0–5% w/v micellar concentration and then decreased at higher concentrations. The rate of transport of phenol was not affected by the presence of micellar phase.
Ionic interaction between surfactant and model drugs affected transport rates of model drugs in emulsion systems. The micellar phase was considered to affect the overall transport rates of model drugs.
Oral Sustained-release Cisplatin Preparation for Rats and Mice
Authors: Nakano Kousuke , Ike Osamu , Wada Hiromi , Hitomi Shigeki , Amano Yukihiko , Ogita Ikuo , Nakai Nobuko , Takada Kanji 
Published: April 2011

Abstract
A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II); cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios.
In-vitro dissolution studies showed that cisplatin release characteristics were zero-order for the formulation cisplatin–ethylcellulose–stearic acid (1:10:5) and levels equilibrated 7 h after the start of the experiment. The availability of cisplatin from this preparation was evaluated both in rats and mice. The cisplatin preparation (20 mg kg−1) was administered orally to rats and the resulting curve of serum cisplatin levels against time was compared with that obtained after intravenous infusion (20 mg kg−1) to rats. By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%. The mean residence time (MRT) of cisplatin solid dispersion was 6.13 ± 0.43 h, whereas the MRT of cisplatin administered by intravenous infusion was 3.89 ± 0.05 h. Serum cisplatin levels were maintained above 0.3 mg mL−1 (believed from our clinical studies to be the minimum effective concentration) for 24 h. The curve of serum cisplatin level against time suggested that cisplatin was released from the solid dispersion preparation in a sustained-release fashion. Similar levels were also maintained in mice for 24 h. The MRT of the cisplatin preparation was 10–16 h in mice, which is longer than that obtained after oral administration of the physical mixture. The serum free-cisplatin concentration was determined to be 0.10 mg mL−1 in mice serum in which the total cisplatin concentration was 0.30 mg mL−1. The free fraction of cisplatin in mice serum was the same as that in human patient serum. Pathological examination showed that this new sustained-release oral cisplatin preparation did not have any side effects on the gastrointestinal tract.
These results suggest usefulness of this new solid-dispersion preparation for oral cisplatin therapy in lung cancer patients.
Encapsulation, Stability and In-vitro Release Characteristics of Liposomal Formulations of Colchicine
Authors: Kulkarni Shirish B , Singh Mandip , Betageri Guru V 
Published: April 2011

Abstract
The severe toxicity and low therapeutic index of colchicine limit its therapeutic use. Encapsulation in liposomes might reduce these toxic effects. The objective of this study was to determine the factors influencing encapsulation of colchicine in liposomes and to optimize the encapsulation parameters.
Colchicine was encapsulated in multilamellar liposomes and large unilamellar liposomes prepared using various phospholipids. The effects of method of preparation, type of vesicle, charge, and concentration of cholesterol on encapsulation of colchicine in liposomes were investigated. Also, stability of colchicine under stress conditions and at various temperatures, and in-vitro release characteristics were determined. A significant difference in encapsulation of colchicine in multilamellar liposomes was observed when prepared by two different methods. Induction of charge on the liposome surface increased encapsulation of colchicine in multilamellar liposomes, but did not affect large unilamellar liposomes. The liposome preparations could withstand simulated transport conditions and frequent changes in temperature. Particle size and concentration of colchicine did not change significantly during storage at various temperatures for six months. In order to retain encapsulated colchicine in liposomes, storage at or below room temperature was found to be suitable. In-vitro release of colchicine from large unilamellar liposomes was biphasic and was influenced by two rate-limiting barriers, the dialysis membrane and the liposome bi-layers.
For optimum encapsulation and stability of colchicine liposomes were prepared from a mixture of 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol and either stearylamine or dicetyl phosphate.
Experiences with the Rectal use of Trimethoprim
Authors: Sallai J , Vernyik Á , Regdon G , Gombkötõ S , Németh J , Regdon G 
Published: April 2011

Abstract
The possibility of rectal use of trimethoprim was studied. The in-vitro liberation of the drug from 24 different suppository bases was examined and the results used to select bases for in-vivo examination.
The in-vitro liberation from the suppositories containing 50–200 mg trimethoprim was studied by the method of dynamic diffusion, and the released drug content was measured spectrophotometrically. The in-vivo examinations were performed in anaesthetized rats. The concentration of trimethoprim in blood was determined by bioassay. The absorption of the drug in the form of oral suspension, rectal solution and suppository was also studied. The pharmacokinetic parameters obtained after blood-level curve fitting were compared by use of the MedUSA 1.6 program. The best in-vivo results were achieved with the lipohydrophilic Witepsol W 35 vehicle containing 10% polysorbate 20 and 10% polysorbate 61 (bioavailability = 63.8%) and with Witepsol W 35 containing 10% polysorbate 60 (bioavailability = 63.8%). The results for hydrophilic Macrogol 1540 vehicle containing 5% of Macrogol 400 were only slightly worse (bioavailability = 52.9%). In the case of the lipohydrophilic Witepsol W 35 vehicle with 10% polysorbate 20 and 10% polysorbate 61 content a significant negative exponential relationship was found between the administered doses and their respective bioavailability values; this tendency was also observed during in-vitro examinations.
When incorporated in the appropriate vehicle trimethoprim was absorbed well. With three vehicles the extent of absorption exceeded that for oral administration on the same model (bioavailability = 38.8%). Trimethoprim rectal suppositories, which are formulated with the vehicles having the best in-vitro and in-vivo results, are suitable for clinical pharmacological investigation.