bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Lactose Particle Size on the Extrusion Properties of Microcrystalline Cellulose-Lactose Mixtures
Authors: Fielden K E , Newton J M , Rowe R C 
Published: April 2011

Abstract
Ram extrusion has been used to assess and compare the flow characteristics and quality of wet powder masses formed from mixtures of water with microcrystalline cellulose and two different particle size samples of lactose. The force-displacement profiles can reveal poor flow properties. Steady state flow was achieved for the mixture containing fine lactose which produced an extrudate of uniform moisture content at all extrusion rates except the lowest (5 cm min−1). Increasing the lactose particle size significantly altered the extrusion properties of the formulation with forced flow predominating and high extrusion pressures observed. Formulations showing that type of extrusion are to be avoided as they produce poor quality extrudate which may be unsuitable for spheronization. Flow visualization studies showed that problems associated with such mixtures are caused by failure to maintain a constant angle of convergence during extrusion, which is essential for maintenance of steady state flow. With the mixture made with coarse lactose, the extrudate quality could be improved by extruding at high velocities, information that may be of significance in the development of formulations for large-scale production. Differences between formulations may be expressed quantitatively by plotting the apparent shear stress-shear rate relationship. The curves are modified by the particle size of lactose included in the mixtures. Such curves have implications in predicting the suitability of an extrudate, produced under particular experimental conditions, for spheronization.
The Bioavailability of a Mixed Micellar Preparation of Vitamin K1, and its Procoagulant Effect in Anticoagulated Rabbits
Authors: Winn M J , White P M , Scott A K , Pratt S K , Park B K 
Published: April 2011

Abstract
We have investigated the pharmacokinetics and procoagulant activity of a new, mixed-micellar preparation of vitamin K1 (MM-K) in male New Zealand White rabbits. Oral administration of MM-K alone caused a significant (P&lt;0·01) increase in the plasma concentrations of vitamin K1 as measured by normal-phase high-performance liquid chromatography (HPLC). Maximum plasma concentrations of vitamin K1 (450 ng mL−1, range 133–824 ng mL−1) were recorded at 3·3 h (range 3–5 h), and were significantly (P &lt; 0·05) greater than those seen after administration of an existing polyethoxylated castor oil preparation (PE-K; Konakion), which were 260 ng mL−1, range 198–390 ng mL−1 (tmax 0·8 h, range 0·4-1·2 h). AUC after MM-K (4·6 μg mL−1 h−1, range 2·1–6·3 μg mL−1) was also significantly (P &lt; 0·05) greater than after PE-K; (1·6 μg mL−1 h−1, range 1·0–2·1 μg mL−1 h−1). However, the bioavailability of vitamin K1 after administration of MM-K was poor (9·4%), and there was considerable intra-individual variability between the concentrations of vitamin K1 recorded in the plasma samples.
Both preparations of vitamin K1 stimulated clotting factor synthesis in rabbits anticoagulated with the potent and long-acting coumarin, brodifacoum. Maximum stimulation of clotting factor synthesis by vitamin K1 after MM-K was 87%, range 44–124% (%PCA). The maximum was seen later (tmax 12 h) than after PE-K (PCA 82%, range 47–125%; tmax 5 h). However, there was considerable intra-individual variability in response to both MM-K and PE-K. Furthermore, there was no difference between the maximum PCA produced by the two preparations. It is concluded that the incorporation of vitamin K1 into bile salt micelles does not enhance either the absorption or efficacy of the vitamin after oral administration.
Reduction by acetylsalicylic acid of paracetamol-induced hepatic glutathione depletion in rats treated with 4,4‘-dichlorobiphenyl, phenobarbitone and pregnenolone-16-α-carbonitrile
Authors: van Bree L , Groot E J , de Vries J 
Published: April 2011

Abstract
The role of enzyme induction in the reduction by acetylsalicylic acid (ASA) of paracetamol-induced hepatic glutathione (GSH) depletion has been studied in rats. Administration of an overdose of paracetamol to control rats resulted in an appreciable decrease of GSH concentration. Pretreatment with the enzyme inducers phenobarbitone, 3-methylcholanthrene (3-MC), pregnenolone-16-α-carbonitrile (PCN) and 4,4′-dichlorobiphenyl (4,4′-DCB) significantly potentiated the paracetamol-induced depletion of GSH. Simultaneous administration of an equimolar dose of ASA resulted in a reduction of the paracetamol-induced depletion of GSH in all instances except for those rats that were not pretreated and those given 3-MC. Benorylate, the ASA ester of paracetamol, depressed rat liver GSH to levels comparable to those produced by the combination of paracetamol and ASA. ASA itself caused only minor changes in liver GSH concentrations. The results demonstrate that ASA causes a diminution of paracetamol-induced GSH depletion in rats with phenobarbitone type of enzyme induction. Inhibition of the formation of the reactive metabolite of paracetamol or reduction of the absorption rate of paracetamol seem to be unlikely as mechanisms underlying the ASA-induced effect. An ASA-mediated effect via changes of the hepatic thiol status is proposed.
RS-61756-007: a potent and selective thromboxane receptor (TP) agonist
Authors: Eglen R M , Whiting R L 
Published: April 2011

Abstract
The activity of RS-61756-007 (methyl-9-oxo, 15 α-hydroxy, 16-phenoxy, 17,18,19,20-tetranor prosta 4,5,13(E)trienoate, 4,5,6 (R), 8(R)) has been assessed at prostanoid receptors (DP, EP1, EP2, FP, IP and TP) in-vitro. The activity profile of RS-61756-007 resembles that of U46619, in that agonism was observed at TP and to a lesser extent at FP receptors, but there was no activity at the remaining subtypes. The actions of both RS-61756-007 and U46619 were antagonized in a similar manner by the TP antagonist SQ 29,548. We conclude that RS-61756-007 is a highly potent TP agonist.
Cefazaflur: kinetics of hydrolysis in aqueous solution, acid dissociation constant and alkaline decomposition to fluorescent products
Authors: Irwin Vincent P , Timoney Richard F 
Published: April 2011

Abstract
The values of the pseudo-first order hydrolysis rate constants in the pH range 1 to 10, and the pKa, were determined for cefazaflur in aqueous solution at 37°C and ionic strength 0·2 M. A fluorimetric assay, based on alkaline hydrolysis at 100°C, was also developed for this compound. The results are consistent with previously reported related properties of other monoprotic cephalosporins.
Prediction of the In-vitro Human Skin Permeability of Nicorandil from Animal Data
Authors: Sato Kiyoshi , Sugibayashi Kenji , Morimoto Yasunori , Omiya Harumi , Enomoto Naoyoshi 
Published: April 2011

Abstract
A method for estimating the in-vitro permeability of human skin to drugs, based on in-vitro permeation studies using animal skins, has been developed. The skins from hairless rats, guinea-pigs, dogs and pigs were used, with nicorandil and deionized water as model drug and solvent in a drug-donor compartment. Diffusion coefficients through the skin barrier, D, and partition coefficients from the drug-donor compartment to skin, K, of the drug, in each species, were calculated by curve-fitting the in-vitro permeation data to a diffusion equation describing the drug permeation through a homogeneous membrane, using a non-linear least squares method. Each barrier thickness, L, was measured microscopically from microtomed skin sections. A positive relationship was found between the skin permeability, Kp, and K value among the four species, but species differences in the D and L values were small in spite of the Kp values being different among the four species. A positive correlation was also observed between the calculated and experimental K values among the four species, and hence it was suggested that the main factor for the species difference in the skin permeability of nicorandil would be the difference in partitioning of the drug from vehicle to stratum corneum. As a result, it has become feasible to predict and estimate skin permeability of nicorandil in humans by substituting each parameter, extrapolated from the animal skin permeation data and partition experiments, in the diffusion equation.
Pharmacokinetic Profile of Idazoxan in the Beagle Dog
Authors: Vallès J , Pruñonosa J , Menargues A , Nomen M , Obach R 
Published: April 2011

Abstract
The α2-antagonist idazoxan (2- (2- (l,4-benzodioxanyl))-2-imidazoline) has been given intravenously and orally to five beagle dogs at 1, 3 and 10 mg kg−1 doses. Idazoxan plasma levels were determined by a HPLC method. After intravenous administration, a linear kinetic behaviour was obtained. Half-life and mean residence time values ranged 105·2–117·1 and 138·1–154·0 min, respectively. Total plasma clearance values and volume of distribution at steady state values ranged from 25·6–32·1 (mL kg−1) min−1 and 3·60-4·36 L kg−1, respectively. After oral administration, time to peak values averaged around 1 h. Dose normalized peak concentration values ranged 161–182 ng mL−1. Bioavailability values ranged 60–88%. Low idazoxan bioavailability has been described in other animal species and attributed to a first-pass effect.
Disposition of the Hypolipidaemic Agent, 2,3-Dihydrophthalazine-1,4-dione, in Sprague Dawley Rats
Authors: Hall Iris H , Oswald C Brent , Wyrick Steven D , Maguire James H , Shrewsbury Robert P 
Published: April 2011

Abstract
The disposition of [14C]2,3-dihydrophthalazine-1,4-dione, a potent hypolipidaemic agent, has been determined after both intravenous and oral administration. Both the routes of administration afforded multi-exponential disposition with an estimated t 1/2 of approximately 75 h. After oral administration, the drug was observed to be absorbed rapidly from the intestine and distributed quickly to all tissues of the body. A large quantity of the 14C-radioactivity was found in the skin and carcass. Approximately 35% of the administered radioactivity was excreted in urine after oral administration and 11% in the faeces. Approximately 66% of the radioactivity excreted in urine was the parent drug. There was evidence of an additional metabolite which accounted for 28% of the urinary radioactive excretion. The parent drug has little serum protein binding, is highly water soluble, and is probably taken up by cells by passive diffusion.
Bioavailability of intramuscular vitamin E acetate in rabbits
Authors: Pedraz J L , Calvo B , Bortolotti A , Celardo A , Bonati M 
Published: April 2011

Abstract
The bioavailability of α-tocopherol acetate and α-tocopherol (vitamin E) was assessed in male rabbits given 50 mg kg−1 doses according to a randomized design. After intramuscular injection of α-tocopherol acetate in colloidal aqueous solution, a mean absolute bioavailability of 65% was calculated for the acetate and 35% for the physiologically active compound, α-tocopherol. Comparison of the kinetic profiles after intravenous and intramuscular administration of the acetate and intravenous injection of α-tocopherol, revealed absorption of α-tocopherol acetate from the site of injection and hydrolysis of the acetate to be potential limiting steps in the bioavailability of α-tocopherol. Intramuscularly injected α-tocopherol acetate in olive oil (the only formulation available in a few European countries) proved completely bio-unavailable. It thus appears necessary to re-assess the utility of current vitamin E supplementation, since the only formulations available offer poor bioavailability.
Hydroxylamine dilates resistance blood vessels of the perfused rat kidney and mesentery
Authors: Moore P K , Burrows L , Bhardwaj R 
Published: April 2011

Abstract
Hydroxylamine (ED50 values, 47 ± 8·9 nmol and 320 ± 39 nmol) dilates resistance arterioles of the perfused noradrenaline-preconstricted rat kidney and mesentery. In this respect hydroxylamine was approximately 63 × and 320 × less potent than acetylcholine (ACh) and 15 × and 128 × less potent than nitroprusside in the two perfused organs studied. The vasodilator effect of hydroxylamine (unlike that of ACh) was unaffected by CHAPS de-endothelialization suggesting that its effect is independent of endothelium-derived relaxing factor (EDRF).
Iontophoretic transport of weak electrolytes through the excised human stratum corneum
Authors: Siddiqui Ovais , Roberts Michael S , Polack Alan E 
Published: April 2011

Abstract
The effect of iontophoresis on the rate of permeation of a number of therapeutically active weak acids and bases through excised human stratum corneum has been examined, over a range of pH values. It has been shown that the amount of ionized drug species present in the drug solution is an important factor in the delivery of acids and bases by this route and that the molecular weight of the drug does not influence the rate of delivery by iontophoresis.
Effect of Particle Shape on the Mixing of Powders
Authors: Wong L W , Pilpel N 
Published: April 2011

Abstract
Mixtures were prepared containing 200 g of 600 μm lactose and 0.5 g of 3 μm calcium carbonate of different particle shapes using a Y cone mixer. Measurements were made of the time required to achieve the acceptable standard deviation of mixing σA and of the segregation that occurred on subsequently vibrating the mixtures. The time taken to achieve σA increased with the irregularity of the particles of both components and the mixtures containing irregular particles segregated less on vibration.
Macrophage Activation for Antitumour Function by Muramyl Dipeptide-protein Conjugates
Authors: Tabata Yasuhiko , Ikada Yoshito 
Published: April 2011

Abstract
A muramyl dipeptide (MDP) has been conjugated directly with various proteins by means of a water-soluble carbodiimide. The enhancement of the antitumour activity of mouse peritoneal macrophages by the MDP-protein conjugates has been investigated to assess the ability of the proteins for targeting MDP to the macrophages. These were activated to inhibit the in-vitro growth of tumour cells much more effectively, when immunoglobulin (IgG), fibronectin (FN), and gelatin conjugates were used than when MDP was used alone. The minimum amount of MDP in both the MDP-gelatin and the MDP-IgG conjugates necessary for macrophage activation was approximately 2000 times lower than the amount of free MDP needed. The macrophages activated by the conjugates exhibited growth inhibitory activity against phenotypically diverse tumour cells. The activity induced by the MDP-gelatin conjugate was higher than that of the MDP-IgG conjugate over the range of MDP concentrations, regardless of the isoelectric point of the gelatin used. When MDP was conjugated with bovine serum albumin (BSA), the antitumour activity of macrophages was reduced as the amount of BSA conjugated increased. With both free MDP and MDP-protein conjugates, the macrophages were more strongly activated, the longer they were pretreated. However, less pretreatment time was needed to potentiate macrophage activation by the MDP-gelatin conjugate than by free MDP. Also, the macrophages pretreated with the MDP-gelatin conjugate could maintain their activated state for longer than those pretreated with free MDP. It is concluded that gelatin is an effective carrier protein for the targeting MDP to macrophages, resulting in their activation.
Influence of Lignocaine on Plasma Protein Binding and Pharmacokinetics of Verapamil in Dogs
Authors: Belpaire Frans M , de Rick Andre , Bourda Alain , de Smet Frits , Rosseel Marie-Therese , Bogaert Marc G 
Published: April 2011

Abstract
The effect of lignocaine (lidocaine) on the plasma protein binding of verapamil has been studied in-vitro and in-vivo in dogs. The binding of verapamil was ca 85%. In-vitro addition of lignocaine at therapeutic concentrations displaced verapamil from its plasma binding sites. Lignocaine in this regard was equipotent with tris(2-butoxyethyl)phosphate, suggesting an interaction at the level of α1-acid glycoprotein binding sites. On in-vivo administration of 4 mg kg−1 in a bolus to dogs in which steady state concentrations of verapamil were present, the free fraction of verapamil increased transiently. During the lignocaine maintenance infusion, it then decreased to a level higher than that before administration of the local anaesthetic. The free verapamil concentrations increased suddenly upon the administration of the lignocaine loading dose, and then returned to values slightly higher than those before lignocaine. After a bolus injection of verapamil during a lignocaine infusion, the verapamil total plasma concentrations were lower than during a saline infusion, but the free concentrations were not different. The volume of distribution of verapamil was increased, whereas the blood clearance had not changed; the lignocaine infusion did not change the hepatic blood flow, as measured by indocyanine green clearance. These results show that lignocaine displaces verapamil in-vitro and in-vivo from its plasma protein binding sites, but the ensuing pharmacokinetic changes do not lead to significant changes in free verapamil concentrations.
Effect of time of dosing relative to a meal on the raft formation of an anti-reflux agent
Authors: Washington Neena , Greaves Jane L , Wilson Clive G 
Published: April 2011

Abstract
Gamma scintigraphy was used in twelve healthy volunteers to establish whether the time of dosing of Liquid Gaviscon relative to a meal influenced its therapeutic action. Indium-113m labelled Liquid Gaviscon was administered to fasted subjects, 30 min after a technetium-99m labelled meal or immediately before ingestion of the meal. The time for 50% of the Gaviscon to empty from the stomach was 0.36 ± 0.13 h, 3.10 ± 0.31 h and 0.68 ± 0.04 h (s.e.m.), respectively. The preparation was found to empty rapidly from the fasted stomach and could not be floated on a meal consumed subsequently. For raft formation to occur, Liquid Gaviscon should be taken 30 min after a meal.
Gastric mucosal cytoprotection in the rat by naftidrofuryl oxalate
Authors: Salim Aws S 
Published: April 2011

Abstract
Ischaemic gastric mucosal injury was assessed in the rat by measurement of the area of the injury produced after 6 h by reserpine (5 mg kg−1 i.p.) or 5-hydroxytryptamine (5-HT) (50 mg kg−1 i.p.). Pretreatment with naftidrofuryl 1 mL, 1% by gavage significantly (P &lt; 0001) protected the rat stomach against the reserpine (24 ± 2.7 mm2 vs 40 ± 4.7 mm2, mean ± s.e.m., n = 10) and 5-HT injury (11.4 ± 1.7 mm2 vs 27 ± 4.1 mm2, mean ± s.e.m., n = 10). Naftidrofuryl 1 mL 2% by gavage was more effective (P &lt; 0.001) in this respect and mucosal injury only developed in 50% of rats injected with reserpine (9.4 ± 1.1 mm5) and 30% of those injected with 5-HT (3.2 ± 0.4 mm2). Administration of naftidrofuryl 1 mL 5% by gavage completely protected the rat against both the reserpine- and 5-HT-induced acute gastric mucosal injury. This protection was not associated with any significant influence on the H+ output.
α2-Adrenoceptor-mediated Inhibitory and Excitatory Effects of Detomidine on Rat Gastric Acid Secretion
Authors: Blandizzi C , Bernardini M C , Natale G , Del Tacca M 
Published: April 2011

Abstract
The effects of the selective α2-adrenoceptor agonist detomidine on gastric acid secretion from pylorus-ligated and stomach-perfused rats have been investigated. In pylorus-ligated rats i.p. injection of detomidine markedly inhibited acid secretion, this effect being prevented by yohimbine or idazoxan. Under the same conditions, idazoxan significantly increased secretion in a dose-independent fashion. In non-vagotomized and vagotomized stomach-perfused rats i.p. detomidine stimulated acid secretion: this excitatory effect was antagonized by idazoxan. The present results suggest that both inhibitory and excitatory gastric secretory effects of detomidine are mediated by α2-adrenoceptors on cholinergic and adrenergic nerves, respectively. The stimulant activity of idazoxan on gastric secretion from pylorus-ligated rats may be interpreted in terms of increased excitatory vagal tone following the blockade of inhibitory α2-adrenoceptors.
Inhibition of gastric H+, K+-ATPase by chalcone derivatives, xanthoangelol and 4-hydroxyderricin, from Angelica keiskei Koidzumi
Authors: Murakami S , Kijima H , Isobe Y , Muramatsu M , Aihara H , Otomo S , Baba K , Kozawa M 
Published: April 2011

Abstract
Two chalcone derivatives, xanthoangelol (I) and 4-hydroxyderricin (II) isolated from Angelica keiskei Koidzumi, inhibited pig gastric H+, K+ -ATPase with IC50 values of 1.8 and 3.3 μM, respectively. The inhibition by I or II was competitive with respect to ATP and was non-competitive with respect to K+. I and II also inhibited K+, stimulated p-nitrophenyl phosphatase, with IC50 values of 1.3 and 3.5 μM, respectively. Proton transport in-vitro was inhibited by I or II, in a dose-dependent manner. I at 100 mg kg−1, i.p. significantly inhibited acid secretion and the formation of stress-induced gastric lesions. These results suggest that the antisecretory effect of I is due to the inhibition of gastric H+, K+-ATPase.
The Effect of Some Anti-inflammatory Agents on Elastase Release From Neutrophils In-vitro
Authors: Adeyemi E O , Chadwick V S , Hodgson H J F 
Published: April 2011

Abstract
In view of the potential role of released polymorphonuclear leucocyte elastase in causing tissue damage, the effect of commonly used anti-inflammatory drugs on elastase release from neutrophils has been studied in-vitro. Elastase release from neutrophils exposed to the synthetic bacterial cell wall peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (10−6 M) was quantitated using a radiometric immunoassay and a functional assay of elastase. Prednisolone and non-steroidal anti-inflammatory drugs inhibited elastase release at concentrations from 0.1 mM-0.1 nM. No inhibition by sulphosalicylic acid, D-penicillamine or chloroquine sulphate was observed. The clinical relevance of these findings is discussed.
The effect of chronic captopril administration on hepatic blood flow of the rat
Authors: Bar-Meir Simon , Prigojin Haia , Bruck Rafael , Krepel Zipora , Avni Yona 
Published: April 2011

Abstract
The effect of chronic captopril administration on indocyanine green (ICG) clearance and hepatic extraction has been studied in the rat using the intact liver for ICG clearance and the isolated perfused liver for ICG extraction. The captopril was added to the drinking water to give a calculated daily intake from 0–45 mg kg−1. Hepatic clearance of ICG was dose related from 16.5 ± 2.4 (control) to 7.2 ± 1.6 mL min−1. kg−1, respectively. The hepatic extraction of ICG was not significantly different (37 ± 6%) from the control value in groups on 4 and 45 mg kg−1 daily. Since ICG clearance and extraction are dependent on hepatic blood, a change in ICG clearance without a change in the extraction reflects a similar change in the hepatic blood flow. This remained unchanged at daily captopril intakes of 1 and 4 mg kg−1 and decreased when the daily intake was 10 mg kg−1 or higher. If these results in the rat are applicable to man, the chronic administration of therapeutic doses of captopril (0.5-2 mg kg−1) will not affect the hepatic blood flow.