bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapidly Absorbed Solid Oral Formulations of Ibuprofen Using Water-soluble Gelatin
Authors: Imai Teruko , Kimura Susumu , Iijima Takeo , Miyoshi Tetsu , Ueno Masao , Otagiri Masaki 
Published: April 2011

Abstract
Rapidly absorbed oral dosage forms of ibuprofen using water-soluble gelatin (hydrolysate of common gelatin: mean mol. wt: 6000) have been studied and compared with tablets prepared with common gelatin (mean mol. wt: 100 000) and commercial tablets. Spray-dried and speed-kneaded powders, two types of granules and tablets were prepared with water-soluble gelatin. The in-vitro dissolution rates of water-soluble gelatin preparations were significantly faster than those of commercial tablets, whereas the tablets prepared using common gelatin had slower dissolution rates than commercial tablets. Water-soluble gelatin enhanced the dissolution rate of ibuprofen by improving the wettability of the drug particle surface by water, without any interaction in solution and the solid state. The absorption behaviour of various preparations was evaluated in four beagle dogs. The peak concentration time (tmax) of the water-soluble gelatin preparations was significantly shorter than that of tablets prepared with common gelatin and commercial tablets. The maximum concentration (cmax) and the area under the serum concentration-time curve (AUC0–10 h) were similar in all cases. The serum concentration profiles of water-soluble gelatin solid preparations were almost the same as those of the solutions. On the other hand, the profiles of the common gelatin tablets were similar to those of the commercial tablets. The mean absorption time (MAT) from water-soluble gelatin preparations was about 0.7 h, while the MAT from commercial tablets and common gelatin tablets was about 1.2 h. The differences in the MAT of water-soluble gelatin preparations and commercial tablets or common gelatin tablets were the same as the differences in mean dissolution time (MDT) in gastrointestinal fluid. The MDTs of the water-soluble gelatin preparations were from 1 to 5 min, so both disintegration and dissolution steps were rapid. The water-soluble gelatin preparations were stable at 40°C and 70% RH for at least 30 days. The results suggest that the water-soluble gelatin is a useful additive to solid ibuprofen formulations as it may initiate a more rapid and uniform dissolution and absorption of the drug.
Microcalorimetric Study for the Binding of Ionic Drugs to Human Erythrocytes and the Ghost Membranes
Authors: Aki Hatsumi , Yamamoto Magobei 
Published: April 2011

Abstract
The binding of phenothiazine derivatives (as cationic drugs) and non-steroidal anti-inflammatory drugs (as anionic drugs) to human erythrocytes and ghost membranes has been compared with respect to their thermodynamic characteristics, by flow microcalorimetry at pH 7.4 and 37°C. From enthalpy-entropy correlation, it was shown that anionic and cationic drugs are bound to different binding sites on the membranes. Phenothiazines bind to a single common site of the erythrocyte membranes with relatively high binding affinities (K = 104-105 M−1). The binding is entropy-driven and characterized by a small negative enthalpy (ΔH) and a positive entropy change (ΔS), reflecting hydrophobic interactions. However, the binding reaction for the intact erythrocytes shows large negative values for both AH and AS. The values of K for the membranes and ΔH for the intact erythrocytes increased with the increase of the hydrophobic character of the substituent group at the C-2 position of the phenothiazine nucleus (H &lt; Cl &lt; CF3). The results indicate that phenothiazines bind and/or penetrate to the inner membranes of the erythrocytes and react with intracellular components such as haemoglobin, while anti-inflammatory drugs bind to the surface protein on the membranes with a lower affinity (K = 103 M−1) than phenothiazines, reflecting the small negative ΔH and positive ΔS for the interaction with intact erythrocytes.
Cerebral Pharmacokinetics of Ipsapirone in Rats After Different Routes of Administration
Authors: Nocon H , Daniel W , Danek L , Melzacka M 
Published: April 2011

Abstract
Ipsapirone, a putative non-benzodiazepine anxiolytic, was extensively metabolized in rats to 1-(2-pyrimidinyl)piperazine (1-PP) which accumulated in the brain. Neither the route of administration (i.p. or p.o.), nor prolonged administration of ipsapirone or 1-PP affected their accumulation in the rat brain. The cytochrome P450 level and ethylmorphine N-demethylase activity in rat liver microsomes were unchanged by chronic treatment with ipsapirone or 1-PP. The results indicate that 1-PP may contribute to the α2-adrenoceptor antagonism of ipsapirone in rats and that chronic treatment with the drug does not affect its biotransformation to 1-PP.
Potent inhibition of prostaglandin inactivation in rabbit gastric antral mucosal slices by selenium ions in-vitro
Authors: Fujita Tadashi , Nakatani Emi , Funaishi Nobuyuki , Sakuma Satoru , Fujimoto Yohko 
Published: April 2011

Abstract
The effect of selenium ions on prostaglandin (PG) catabolism and synthesis in rabbit gastric antral mucosal slices has been examined. Selenium ions had a potent inhibitory effect on the inactivation process for PGE2 and PGF2α. Simultaneously, the levels of PGE2 and PGF2α were increased. These results suggest that selenium ions have the potential to increase the levels of biologically active PGs in gastric mucosa by preventing their inactivation and that this effect may represent some pharmacological action of selenium ions.
Cortisone: a potent GABAA antagonist in the guinea-pig isolated ileum
Authors: Ong Jennifer , Kerr David I B , Capper Hugh R , Johnston Graham A R 
Published: April 2011

Abstract
In the guinea-pig isolated ileum, cortisone at 0.001–10 nM induced a non-competitive, dose-dependent antagonism of GABAA-receptor-mediated contractile responses to applied GABA, depressing the maximum contractile response to GABA (100 μM), without affecting contractile responses to acetylcholine or cholinergic twitch contractions. At higher concentrations (&gt;10 nM), cortisone depressed contractile responses to acetylcholine (10–100 nM) and cholinergic twitch responses to transmural stimulation. Cortisone is thus the most potent non-competitive antagonist at GABAA-receptor complexes in the guinea-pig ileum. From molecular modelling, sterically there appeared little difference between cortisone and cortisol, the latter being an enhancer of GABAA-receptor-mediated action in the ileum. However, there were significant differences in electrostatic potentials between the two steroids, due to the different levels of oxidation at C11 which may contribute to such opposing actions.
Enhancement of Morphine Clearance Following Intravenous Administration by Oral Activated Charcoal in Rabbits
Authors: El-Sayed Y M , Hasan M M 
Published: April 2011

Abstract
A single dose of activated charcoal (10 g) significantly reduced the half-life of elimination (1.02 ± 0.10 and 0.70 ± 0.04 h for the control and treated groups, respectively) and mean residence time (1.01 ± 0.12 and 0.76 ± 0.05 h for the control and treated groups, respectively) of morphine in rabbits. A 40% increase in the systemic clearance (85.73 ± 7.72 and 122.64 ± 16.32 mL min−1 kg−1 for the control and treated groups, respectively) and a 30% decrease in AUC (204.38 ± 22.20 and 140.03 ± 19.32 μg h L−1 in the control and treated groups, respectively) were also noted. Charcoal administration did not significantly alter the volume of distribution (Varea and VSS) or the apparent distribution half-life. A two-compartment model adequately described morphine kinetics in control and treated rabbits; charcoal administration produced a significant increase in the tissue compartment rate constant (K21). This finding indicates that activated charcoal not only enhances the systemic elimination of morphine, but also accelerates the rate of transfer of morphine from the tissue compartment to the central compartment.
Prostaglandin E2-mediated Stimulation of Mucus Synthesis and Secretion by Rhein Anthrone, the Active Metabolite of Sennosides A and B, in the Mouse Colon
Authors: Yagi Teruyo , Miyawaki Yoshie , Nishikawa Atsuko , Horiyama Shizuyo , Yamauchi Kazuko , Kuwano Shigeaki 
Published: April 2011

Abstract
Rhein anthrone, the active metabolite of sennosides A and B, stimulated PGE2 release into the mouse colonic lumen. At 6.24 mg kg−1, it decreased net water and Na+ absorption significantly in the case of water, but could not reverse the net absorption in mouse ligated colon, although it enhanced net K+ secretion. Pretreatment with indomethacin diminished the effects of rhein anthrone except on K+ net secretion. Rhein anthrone or PGE2 markedly stimulated mucus secretion and synthesis in mouse ligated colon. The enhanced mucus secretion and synthesis induced by rhein anthrone were significantly suppressed by pretreatment with indomethacin. Our results have shown that the colonic secretion of water and electrolytes mediated by PGE2 is partly involved in the rhein anthrone-induced diarrhoea but that in mice, the mucoid diarrhoea induced by rhein anthrone results mainly from PGE2-mediated mucus synthesis and secretion in the colon.
A Comparison of the Effects of an Extract of Feverfew and Parthenolide, a Component of Feverfew, on Human Platelet Activity In-vitro
Authors: Groenewegen W A , Heptinstall S 
Published: April 2011

Abstract
Extracts of the herb feverfew inhibit human blood platelet aggregation and secretion induced by a number of agents in-vitro and this may relate to the beneficial effects of feverfew in migraine. We previously identified several compounds with antisecretory activity in human blood platelets using adrenaline as the stimulant. In the present study, we have compared the inhibitory activity of one of these compounds, parthenolide, with that of crude feverfew extract. The effects of both on [14C]5-HT secretion from platelets and on platelet aggregation induced by a number of different stimulants were determined. The activating agents studied included the phorbol ester PMA, ADP, arachidonic acid, collagen, the thromboxane mimetic U46619, the calcium ionophore A23187, the diacylglycerol analogue OAG and adrenaline. The results show that there are marked similarities between the effects of feverfew extract and of parthenolide on both [14C]5-HT secretion and platelet aggregation, which is consistent with the effects of feverfew extract on platelets being brought about by parthenolide or similar compounds in the extract. Only in one case, when A23187 was used as the stimulatory agent, was there any discrepancy, which may have been due to materials in the extract other than parthenolide. Both feverfew extract and parthenolide were more effective as inhibitors of the [14C]5-HT secretion and aggregation induced by some agents and not others, and were most effective as inhibitors of the [14C]5-HT secretion (but not the aggregation) induced by PMA. This suggests that the effects of feverfew/parthenolide on the protein kinase C pathway warrants further study.
Effect on Cerebral Blood Flow of Orally Administered Indomethacin-loaded Poly(isobutylcyanoacrylate) and Poly(DL-lactide) Nanocapsules
Authors: Ammoury Nazih , Fessi Hatem , Devissaguet Jean-Philippe , Allix Monique , Plotkine Michel , Boulu Roger G 
Published: April 2011

Abstract
Nanocapsules, containing indomethacin, were prepared either by interfacial polymerization of isobutylcyanoacrylate monomers or by interfacial deposition of a preformed (DL-lactide) polymer. In-vitro release of indomethacin from nanocapsules was dependent on the pH of the sink solution and was enhanced by addition of albumin. A decrease in cerebral blood flow was noted 15 min after oral administration to rats of indomethacin nanocapsules (5 mg kg−1) and lasted over 3 h. Empty nanocapsules had no effect. Since release of indomethacin from nanocapsules is unlikely to occur in the lumen of the stomach, due to unsuitable pH conditions, and nanocapsules have been previously shown to be able to cross the intestinal barrier, to reach the villi vessels intact and to protect against the ulcerating effect of the free drug, it is suggested that the rapid onset of the pharmacological effect was sufficiently induced by free indomethacin released in the plasma following absorption of the intact nanocapsules.
Preferential Decrease in Dopamine Utilization in Prefrontal Cortex by Zopiclone, Diazepam and Zolpidem in Unstressed Rats
Authors: Boireau A , Dubedat P , Laduron P M , Doble A , Blanchard J C 
Published: April 2011

Abstract
This study has compared the effects of a cyclopyrrolone, zopiclone, a benzodiazepine, diazepam, and an imidazopyridine, zolpidem, on dopamine (DA) and DOPAC levels, and DA utilization (DOPAC/DA ratio) in rat striatum and prefrontal cortex. The endogenous levels of DA were significantly increased by both zopiclone (2.5, 10 and 40 mg kg−1 p.o.) and diazepam (10 and 40 mg kg−1 p.o.) in the prefrontal cortex, whereas striatal DA content was significantly increased only with the highest dose of diazepam (40 mg kg−1 p.o.). Diazepam (10 and 40 mg kg−1 p.o.) decreased cortical level of DOPAC more markedly than striatal levels, whereas zopiclone (40 mg kg−1 p.o.) only slightly decreased striatal DOPAC levels. Zopiclone and diazepam dose-dependently decreased DA utilization, an effect which was more marked in prefrontal cortex than in striatum. This result was confirmed with zolpidem, another benzodiazepine ligand. Zopiclone was most potent at decreasing DA utilization at the cortical level. The diazepam-induced decreases in DA metabolism and utilization were antagonized by Ro 15–1788, suggesting that the effects seen were mediated by specific benzodiazepine receptors. Thus, our results clearly show that ligands acting on the benzodiazepine receptor/GABA receptor/chloride ionophore complex can decrease the utilization of dopamine in unstressed rats. The preferential decrease in cortical DA utilization induced by benzodiazepine ligands may be compared to the well-known activation by stress of the mesocortical DAergic system.
The Effects of Haematocrit, Plasma Protein Concentration and Temperature of Drug-containing Blood In-vitro on the Concentrations of the Drug in the Plasma
Authors: Tamura Akira , Sugimoto Kazumoto , Sato Takashi , Fujii Tatsuzo 
Published: April 2011

Abstract
Factors which influence the plasma drug concentrations in whole blood have been investigated in-vitro using human blood containing radio-labelled phenytoin or chlorpromazine. Phenytoin (3.55 μg mL−1, 0.01 mM) or chlorpromazine (2.74 μg mL−1, 0.01 mM) was mixed with normal or modified blood and the plasma drug level was measured. Plasma phenytoin and chlorpromazine levels decreased with decrease in the protein concentration of plasma, but were not influenced by addition of y-globulin to the blood specimen. Plasma phenytoin levels increased with an increase in haematocrit from 20 to 45%, whereas the chlorpromazine level remained constant. The partition coefficients of phenytoin and chlorpromazine between blood cells and plasma were almost the same at various haematocrit values. By cooling the blood containing each drug to 4°C, plasma phenytoin and chlorpromazine levels were higher compared with those at 37°C. Similar temperature effects on the drug levels in plasma were obtained when the washed erythrocytes were resuspended in albumin medium, but not when resuspended in saline.
Effect of structural variations of non-ionic surfactants on surface properties: surfactants with semi-polar hydrophobes
Authors: Attwood D , Elworthy P H , Lawrence M J 
Published: April 2011

Abstract
The surface properties of a series of non-ionic surfactants in which a polar group (either an ether or a keto group) has been introduced into a hydrocarbon chain of octadecylpolyoxyethylene glycol monoether (C18E17–19) have been investigated. Surface tension measurements indicated that the critical micelle concentrations for these semi-polar surfactants in aqueous solution were all significantly higher than those of C18E22, the corresponding unsubstituted octadecylpolyoxyethylene glycol monoether. The minimum areas per molecule of the semi-polar surfactants in the surface monolayer were all larger than the area obtained for C18E22, from which it was concluded that the hydrophobe, and not the polyoxyethylene chain was the main determinant of surface area.
Differential scanning calorimetry characterization of process-induced variations in an ointment base
Authors: Timmins Peter , Browning Ivan , Payne Nicholas I 
Published: April 2011

Abstract
Preparation of an experimental emollient wax-gelled ointment base by two processes differing only in cooling rate produced material with markedly different physical properties. Differential scanning calorimetry showed that a major endotherm, possibly related to a phase change in a major triglyceride wax component, Synchrowax HGLC, was different in the two products. Mean enthalpies for this major endotherm for the two products were 7.36 J g−1 (s.d. = 0.49, n = 5) in slow cooled samples and 4.35 J g−1 (s.d. = 0.21, n = 5) in fast cooled samples. The degree of order of the Synchrowax HGLC in the ointment is suggested as being different in the two preparations and it is this that controls the physical properties of the ointment.
In-vitro antibacterial activity of noxythiolin and taurolidine
Authors: Blenkharn J Ian 
Published: April 2011

Abstract
The minimum inhibitory concentrations (MIC) of noxythiolin and taurolidine were determined for strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Tests were performed in broth alone and in broth plus 25% v/v serum or 25% v/v urine. Inoculum density was either 103, 105 or 107 colony forming units per mL−1. Slight inoculum-dependent variation in the activity of both agents was observed for some, but not all, strains of P. aeruginosa and S. aureus. A more pronounced medium-dependent increase in activity was observed with both drugs, with up to 8-fold reduction of values for MIC when tested in the presence of serum or urine. These observations may help to clarify the disparity between the observed clinical efficacy of these agents and relatively poor in-vitro activity when tested using conventional methods in synthetic media.
Comparative effects of (+)-propranolol and nonoxynol-9 on human sperm motility in-vitro
Authors: Gadd A L , Curtis-Prior P B 
Published: April 2011

Abstract
Using the modified transmembrane migration method to measure sperm motility, it was shown that the surfactant nonoxynol-9 alone, was twice as potent as (+)-propranolol alone as a spermicidal agent. Addition of (+)-propranolol to nonoxynol-9 shifted the dose-response curve to the left of the curves for either component alone, and a surprising synergistic action was evident. These observations may form the basis for the development of a new advantageous topical contraceptive combination product.
The relative dependence of calcium antagonists and neuroleptics binding to brain and heart receptors on drug lipophilicity
Authors: Rojratanakiat Winyu , Hansch Corwin 
Published: April 2011

Abstract
QSAR analysis of the binding of calcium antagonists to brain and heart tissue shows that relative binding to brain tissue increases with increasing octanol/water partition coefficients. A number of antischizophrenic drugs follow the same pattern.
Evaluation of Release from Selected Thermosoftening Vehicles
Authors: Kopcha Michael , Lordi Nicholas G , Tojo Kakuji J 
Published: April 2011

Abstract
Release of D&C Yellow No. 10 and anhydrous theophylline have been determined from a thermosoftening, hydrophilic matrix, Gelucire 50/13, incorporating a water-soluble additive, polyethylene glycol 4000. As additive level increased, release also increased. The effect of mixtures of Gelucire 50/13 (G50/13) and Gelucire 50/02 (G50/02) on release was also investigated as a function of temperature and pH. As the level of G50/02 increased, release decreased and became predominantly diffusional. As temperature was increased, release changed from diffusion to a mixed model of both diffusion and erosion. At basic pH, release from these composite systems became more erosional in character, possibly reflecting partial hydrolysis of the ester-linked matrices. Diffusion coefficients and apparent diffusion coefficients were calculated in G50/02 and G50/13 matrices, respectively, and were in agreement with published data.
Epithelium Modulates the Reactivity of Sensitized Guinea-pig Trachea: Influence of the Surface of Drug Entry
Authors: Iriarte C F , Pascual R , Villanueva M M , Román M , Ortiz J L , Cortijo J , Morcillo E 
Published: April 2011

Abstract
A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings isolated from sensitized guinea-pigs was applied to study the role of the epithelium in modulating responses to KCl, acetylcholine, histamine and antigen (bovine serum albumin, BSA). Epithelium removal did not alter the responsiveness or sensitivity of tracheal rings to KCl. In contrast, a leftward shift occurred for concentration-response curves to acetylcholine (concentration ratio (CR) = 4·1), histamine (CR = 2·9) and BSA (CR = 33·9) entering from the mucosal surface of de-epithelialized trachea. This shift was not associated with changes in the maximal effect of the spasmogens. Response to the adventitial entry of these spasmogens was not altered by epithelial stripping. These results confirm that the epithelium modulates tracheal responses to certain spasmogens including antigen challenge. This role was exclusively exerted for mucosal drug entry. The mechanism underlying this protective effect of epithelium remains to be determined.
Influence of Calcium Entry Blockers and Calmodulin Inhibitors on 5-Hydroxytryptamine-, Potassium- and Calcium-induced Contractions in Human Umbilical Artery In-vitro
Authors: Medeiros Yara S , Calixto João B 
Published: April 2011

Abstract
The effects of calcium (Ca2+) withdrawal, Ca2+ entry blockers and calmodulin inhibitors on the contractile responses to 5-hydroxytryptamine (5-HT), K+ and CaCl2 have been studied in human isolated umbilical artery. Following Ca2+ withdrawal from the medium (30 min), both 5-HT- and K+ -induced contractions were virtually abolished. Ca2+ entry blockers (nifedipine, verapamil, diltiazem and cinnarizine) were significantly more effective in inhibiting 5-HT- than K+-induced contractions. In relation to calmodulin inhibitors, trifluoperazine inhibited all types of contractions, whereas W-7 (N-6-aminohexyl-5-chloro-1-naphthalene sulphonamide) only inhibited 5-HT- and CaCl2-induced contractions. All drugs inhibited CaCl2-induced contractions in a non-competitive manner. These findings indicate that the mechanisms by which these drugs exert their inhibitory effects on human umbilical artery are markedly different from those reported in other vascular beds.