bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Antigen-induced Arthritis in Rabbits with Liposome-entrapped Methotrexate Injected Intra-articularly
Authors: Foong W C , Green K L 
Published: April 2011

Abstract
Rabbits with a bilateral antigen-induced arthritis were injected intra-articularly in one joint with methotrexate as the free drug or entrapped in liposomes. Free methotrexate (1 mg) injected as a single dose at the time of antigen challenge, suppressed the development of joint swelling and the rise in skin surface temperature of treated joints by 20–30% compared with contralateral control arthritic joints. The beneficial effect of methotrexate occurred within 24 h of injection and was maintained for at least 56 days. However, methotrexate was ineffective in suppressing arthritis when injected 7 days after antigen challenge. Liposomal methotrexate suppressed the development of arthritis at a dose one-tenth that of the free drug and it was also effective in suppressing arthritis of 7 days duration, although significant beneficial effects of liposomal methotrexate were delayed for 10 to 14 days after injection. Neither free nor liposomal methotrexate was effective in suppressing an established arthritis, having no significant effect on joint swelling or skin surface temperature when injected 21 and 35 days after antigen challenge. At the end of the study, 8 or 9 weeks after induction of arthritis, the joints were examined morphologically and histologically. Free methotrexate generally had no significant effect on joint pathology. However, liposomal methotrexate suppressed the development of synovial hyperplasia, cellular infiltration and the erosion of cartilage and bone when injected at the time of antigen challenge or 7 days later, but affected none of these parameters in an established arthritis of 3 weeks duration.
Quinine impairs quinidine clearance in rat perfused liver
Authors: Mihaly George W , Scott Haydn , Hyman Mark K , Morgan Denis J , Smallwood Richard A 
Published: April 2011

Abstract
We have examined the disposition of the cinchona alkaloids quinine and quinidine in the rat recirculating isolated perfused liver preparation. When administered as separate 1 mg doses, the hepatic clearances of quinine and quinidine were similar to the hepatic perfusate rate of 10 mL min−1. When 1 mg of each was administered simultaneously, mean hepatic clearance of quinine was unchanged (9·00 ± 2·20 mL min−1 separate dosage, n = 7; 6·87 ± 1·77 mL min−1 simultaneous dosage, n = 7; P &gt; 0·05). By contrast, mean hepatic clearance of quinidine was reduced significantly by concomitant quinine (10·6 ± 1·72 mL min−1 separate dosage, n = 7; 4·82 ± 1·25 mL min−1 simultaneous dosage, n = 7; P &lt; 0·05). There was no significant difference in volumes of distribution when each alkaloid was administered separately (131 ± 46 mL quinine, 129 ± 21 mL quinidine; P &gt; 0·05) but concomitant quinine administration increased quinidine volume of distribution to 169 ± 30 mL (P &lt; 0·05). Four further experiments with simultaneous dosages of 0·5 mg of each alkaloid produced similar findings, indicating that the interactions did not derive from nonlinear drug disposition.
K+ Concentration influences methohexitone inhibition of K+-stimulated release of [3H]noradrenaline from minislices of rat cerebral cortex
Authors: Jones C A , Silvers K M 
Published: April 2011

Abstract
This study investigated the effect of methohexitone, a barbiturate anaesthetic, with variation of the K+ concentration used to stimulate [3H]noradrenaline release from superfused minislices of rat cerebral cortex. The amount of [3H]noradrenaline released by K+-stimulation depended on the concentration of K+ used (increasing release was seen at 10–50 Mm K+). Methohexitone (10−7-3 × 10−4 m) added to the superfusing medium did not alter the basal efflux of [3H]noradrenaline, but high concentrations inhibited K+-stimulated release. Using 12·5 Mm K+, inhibition of release was observed only at 10−4 m methohexitone (48% inhibition); the effect of 25 Mm K+ was reduced by 3 × 10−5 m (72% inhibition) and higher concentrations while release stimulated by 50 Mm K+ was inhibited by 10−5 m methohexitone (30% inhibition) and higher concentrations.
Properties of Human Albumin Microparticles Prepared by a Chilled Cross-linking Technique
Authors: Oner L , Groves M J 
Published: April 2011

Abstract
Examination of conditions needed to form albumin microparticles (in the 1–5 μm diam. size range) by glutaraldehyde cross-linking, at low temperature (–15°C), suggested that the particles formed very rapidly over a short time scale and at low concentrations of cross-linking reagent. Detailed analysis showed that the particles increased in size with time of reaction and with an increase in glutaraldehyde concentration. Evaluation of the particle matrix using a dilute trypsin digestion process suggested that the above factors may influence the internal composition since the particles dissolved less rapidly than might be anticipated from a consideration of particle diameter alone.
Statistical Moments in Pharmacokinetics: Models and Assumptions
Authors: Dunne Adrian 
Published: April 2011

Abstract
The modelling basis of statistical moments in pharmacokinetics is considered and the associated assumptions and restrictions highlighted. Both deterministic and statistical models are described and they are seen to give identical results on the basis of equivalent assumptions. It is shown that it is not necessary to assume that all kinetic processes are first order and that some of the pharmacokinetic parameters may be dependent on the dose of administered drug and on the route of administration.
A Pharmacological Comparison of the Receptors Mediating Contractile Responses to 5-Hydroxytryptamine in the Rat Isolated Caudal Artery and Fundic Strip
Authors: Growcott James W , Cox Barry , Blackburn Thomas P 
Published: April 2011

Abstract
Contractile responses to 5-hydroxytryptamine (5-HT) and to a number of 5-HT-receptor agonists have been compared on the rat isolated caudal artery and stomach fundic strip. On the caudal artery, 5-HT was the most potent agonist tested. The 5-HT1-like agonist, 5-carboxamidotryptamine (5-CT), was less potent than 5-HT and produced a lower maximum response. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and RU24969 (5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole) were inactive as agonists and 8-OH-DPAT was not an antagonist. Ketanserin, ICI 169,369 (2-(2-dimethylaminoethyl-thio)-3-phenylquinoline hydrochloride) and ICI 170,809 (2-(2-dimethylamino-2-methylpropylthio)-3-phenylquinoline hydrochloride) were competitive antagonists of 5-HT on this preparation, indicating that 5-HT is acting via 5-HT2 receptors. In contrast, all the agonists produced contractions of the fundic strip (rank order of potency, 5-HT = 5-CT &gt; RU24969 &gt; 8-OH-DPAT). The maximum response to RU24969 was significantly lower than the maximum responses to the other agonists. Ketanserin was only a weak antagonist of 5-HT in the fundic strip, demonstrating that 5-HT2 receptors were not involved, but ICI 169,369 and ICI 170,809 were non-surmountable antagonists of 5-HT responses, as were methysergide and methiothepin. Since ICI 169,369 and ICI 170,809 are devoid of activity at 5-HT3 and 5-HT4 receptors, then these two subtypes would not appear to be implicated, a view that was confirmed in the case of 5-HT3 receptors by experiments using ondansetron. Since radioligand binding studies have shown that ICI 169,369 and ICI 170,809 have high affinity for 5-HT1C sites, α-methyl-5-HT, an agonist claimed to be selective for 5-HT1C and 5-HT2 receptors, was also tested on the fundic strip in the presence of ketanserin. This compound acted as an agonist and was antagonized in a competitive manner by ICI 170,809. Therefore, these results suggest that the receptors mediating contractile responses to 5-HT in the rat fundic strip are more similar to the 5-HT1C subtype than any of the other subtypes that have been described previously.
Synthesis, Properties, and Intratumoral Evaluation of Mitoxantrone-loaded Casein Microspheres in Lewis Lung Carcinoma
Authors: Knepp W A , Jayakrishnan A , Quigg J M , Sitren H S , Bagnall J J , Goldberg E P 
Published: April 2011

Abstract
Smooth, round, uniform bovine casein microspheres of 1–5 and 10–20 μm size were readily prepared by a steric stabilization technique previously developed in this laboratory for synthesis of albumin microspheres. The avid phagocytic uptake of casein and albumin microspheres was demonstrated with fluorescein-labelled microspheres using a macrophage-like mouse myelomonocytic leukaemia cell line. Post-synthesis loading of 25% mitoxantrone was achieved for casein microspheres containing 20% polyglutamic acid. Preliminary intratumoural chemotherapy experiments with a mouse Lewis lung carcinoma indicated that mitoxantrone and mitoxantrone-loaded casein-polyglutamic acid microspheres exhibited lower toxicity when administered intratumorally.
Effects of age on α1-adrenoceptor subtypes in the heart ventricular muscle of the rat
Authors: Gascón Silvia , Dierssen Mara , Màrmol Frederic , Vivas Nuria M , Badia Albert 
Published: April 2011

Abstract
The effects of ageing on α1-adrenoceptor subtypes have been examined in heart ventricular muscle of young (2–3 months) and middle-aged (18 months) Sprague-Dawley rats. Radioligand binding studies with [3H]prazosin revealed an age-related loss of binding sites (Bmax 56·7 ± 1·93 fmol (mg protein)−1 age 2 months vs 31·7 ± 2·45 fmol (mg protein)−l age 18 months) not followed by changes in the dissociation constant value (Kd 0·16 ± 0·03 nm age 2 months and 0·10 ± 0·03 nm age 18 months). Competition curves with WB 4101 showed two distinct sites with different affinities, the proportion of sites with high affinity being similar for both age groups (22·2 ± 1·89% vs 17·8 ± 1·96% for animals aged 2 and 18 months, respectively). Agonist displacement curves of [3H]prazosin indicate the existence of two different affinity sites for the agonist, that are maintained regardless of the ageing process (Rhigh= 16·2 ± 1·54% and Rlow = 83·8 ± 1·89% in rats aged 2 months and Rhigh= 16·3 ± 3·23% and Rlow = 83·7 ± 3·95% in rats aged 18 months). The fractional inactivation of α1-adrenoceptors by chloroethylclonidine resulted in a loss of [3H]prazosin specific binding, and a percentage of 22·5 ± 0·95 and 22·6 ± 4·2 of remaining binding sites for the groups of 2 and 18 months of age, respectively. The percentage of chloroethylclonidine-insensitive [3H]prazosin binding sites was similar to those with high affinity for WB 4101. The present study confirms a decline of α1-adrenoceptors with increasing age and reveals that the equilibrium of the expression of the two existing subpopulations of the receptor is maintained during ageing.
Increased ex-vivo colonic generation of PAF induced by diphenylmethane stimulant laxatives in rats, mice, guinea-pigs and rabbits
Authors: Izzo A A , Mascolo N , Autore G , Di Carlo G , Capasso F 
Published: April 2011

Abstract
The effects of in-vivo treatment with bisacodyl, phenolphthalein, picosulphate, sulphosuccinate, mannitol and lactulose laxatives were examined on the ex-vivo formation of platelet-activating factor (PAF) by duodenum and colon of rat, mouse, guinea-pig and rabbit. Bisacodyl (10 mg kg−1), phenolphthalein (20 mg kg−1) and picosulphate (10 mg hg−1), but not sulphosuccinate (40 mg kg−1), mannitol (50 mg kg−1) or lactulose (50 mg kg−1), at doses that all caused laxation, markedly increased PAF in the colon (P &lt; 0·01) but not in the duodenum. Intraluminal release of acid phosphatase was also significantly increased in the colon of rats treated with bisacodyl, phenolphthalein and picosulphate, but not in colons of animals treated with sulphosuccinate, mannitol or lactulose. The data show that enhanced generation of PAF is associated with the colonic damage induced by diphenylmethane laxatives, but do not show whether this is a cause or a consequence of the pathophysiological changes.
Ciliotoxicity of methyl- and propyl-p-hydroxybenzoates: a dose-response and surface-response study
Authors: Jian L , Po A Li Wan 
Published: April 2011

Abstract
The effect of methyl-p-hydroxybenzoate (methyl para-ben, MHB) and propyl-p-hydroxybenzoate (propyl paraben, PHB) on ciliary beat frequency was investigated using surface-response methodology. Both compounds are shown to be ciliotoxic at concentrations equal to or lower than those in use for preserving aqueous formulations. The dose-response curves show the typical sigmoidal pattern. Interaction by the two compounds is evidenced by the curved response surface for ciliotoxicity.
Emulsified Perfluorochemicals as Respiratory Gas Carriers: Recovery of Perfluorodecalin Emulsion Droplets from Rat Tissues
Authors: Lowe K C , Washington C 
Published: April 2011

Abstract
To further understand the in-vivo biokinetic behaviour of perfluorochemical (PFC) emulsions, male rats were injected (10 mL kg−1) with 30% (w/v) emulsified perfluorodecalin (FDC) and uptake into tissues assessed. At 72 h after injection, the mean (±s.e.m.) diameters of FDC droplets recovered from liver and spleen were 2·24 ± 0·04 and 2·78 ±0·10 μm, respectively; droplets recovered from lung after 72 h (mean: 1·73 ±0·13 μm) were significantly smaller (p &lt; 0·01). After 7 days, FDC droplet diameters in liver had increased to 3·31 ± 0·13 μm (P &lt; 0·01) and those in lung to 2·71 ± 0·14 μm (P &lt; 0·01); droplets in spleen after 7 days (2·22 ± 0·09 μm) were similar to those at 72 h. These data support the hypothesis that significant initial coalescence of FDC droplets occurs in the rat liver and spleen, with further coalescence in the liver up to 7 days. The mean percentage of the injected FDC dose recovered from the liver after 72 h was 2·2 ± 0·4%, and after 7 days was 0·07 + 0·05% (P &lt; 0·01). A smaller decrease in the percent injected FDC in spleen also occurred over the same period (72 h: 1·9 ± 0·3%; 7 days: 0·8 ± 0·5%; P &lt; 0·01). The percent injected FDC in lung was similar at 72 h (0·007 ± 0·004%) and 7 days (0·005 ±0·001 %). FDC was undetectable (&lt; 0·001 %) in all blood samples. The greater rate of FDC elimination from the liver than from the spleen may be related to differences in the rates of reticuloendothelial system processing between these organs.
Effect of an Histaminergic H3 Agonist on the Non-adrenergic Non-cholinergic Contraction in Guinea-pig Perfused Bronchioles
Authors: Burgaud J L , Oudart N 
Published: April 2011

Abstract
From the bronchioles of guinea-pigs, preparations were isolated for registration of perfused pressure on electrical field stimulation (EFS) and by application of drugs. The perfused bronchioles contracted when EFS was applied in the presence of atropine and phentolamine suggesting a non-adrenergic non-cholinergic (NANC) response. (R)-α-Methylhistamine (methylhistamine), a selective H3 agonist, reduced the NANC bronchoconstrictor response in a concentration-dependent manner. β-Adrenoceptors, muscarinic and histamine (H1) and H2 receptor) antagonists, epithelial removal and cyclooxygenase inhibition had no effect on this inhibitory action of methylhistamine whereas the H3 antagonist, thioperamide, reduced the inhibitory effect of methylhistamine with a Ki value of 2·98 × 10−9 m. Methylhistamine had no effect on the concentration-dependent contraction induced by exogenous substance P and neurokinin A, demonstrating that an H3 receptor might inhibit the release of transmitter from NANC nerves on guinea-pig perfused bronchioles in-vitro.
Effect of Fepradinol on Rat Hind Paw Oedema Induced by Several Inflammatory Agents
Authors: Masso J M , Conde J R , Villar A M , Martorell J 
Published: April 2011

Abstract
Fepradinol is an effective non-steroidal anti-inflammatory agent. The effect on rat paw oedema induced by various phlogistic agents was investigated. The inhibitory effect of fepradinol (25 mg kg−1, p.o.) on dextran-induced oedema was nearly equal to that of cyproheptadine (10 mg kg−1, p.o.). On oedema induced by platelet-activating factor only fepradinol (25 mg kg−1, p.o.) and phenidone (100 mg kg−1, p.o.) clearly inhibited the inflammatory process. Both the above induced oedemas are thought to be unrelated to prostaglandins in the rat system and therefore, the anti-inflammatory activity against them is not shared by selective cyclo-oxygenase inhibitors. Fepradinol (25 mg kg−1, p.o.) displayed an inhibitory effect on the early and late stage of kaolin- and nystatin-induced oedemas in contrast with indomethacin (10 mg kg−1, p.o.) and piroxicam (10 mg kg−1, p.o.) which only inhibited the late stage. The results obtained in this study confirm that fepradinol is a potent anti-inflammatory agent and indicate that its mechanism of action is different from that of other anti-inflammatory compounds.
Incorporation of alphaxalone into different types of liposomes
Authors: Dean T P , Hider R C 
Published: April 2011

Abstract
The poor solubility of steroid anaesthetics in water has been a serious drawback in the development of clinically acceptable intravenous formulations. The use of Cremophor EL to solubilize steroids such as alphaxalone led to unacceptable hypersensitivity reactions and consequent withdrawal of this anaesthetic. In principle, liposomes can act as a safe solvent for the intravenous administration of alphaxalone. We report the incorporation of [14C]acetylated alphaxalone in both multilamellar vesicles and stable plurilamellar vesicles prepared from a range of amphiphiles including synthetic polyhydroxyl lipids. For both types of preparations, addition of cholesterol to phosphatidylcholine-based lipids caused an increase in encapsulation efficiency. Maximum encapsulation was achieved with the stable plurilamellar vesicle preparation of 1-stearyl-2-myristylglycerate-3, N-methylglucamine: cholesterol: egg phosphatidylcholine (78%). The rate of efflux of this anaesthetic from a range of liposomes was measured in serum. The highest rate (85% after 30 min) was observed with an equimolar egg phosphatidylcholine: cholesterol stable plurilamellar vesicle preparation. From these studies it can be concluded that liposomes offer a suitable alternative for intravenous delivery of steroidal anaesthetics.
Calorimetric study on the solubilization of butanol by alkylphosphate and alkylphosphate-lecithin systems
Authors: Trotta M , Fubini B , Gallarate M , Gasco M R 
Published: April 2011

Abstract
Microcalorimetric studies on alkylphosphate-butanol and alkylphosphate-butanol-lecithin systems were carried out as a first step to study the role of butanol (used as cosurfactant) in the formation of microemulsions. The enthalpy of solubilization: ΔH, of the same amount of butanol (1·806 mol kg−1) in aqueous sodium monoalkyl-phosphates, with a hydrocarbon chain varying from 6 to 10 carbon atoms, was investigated as a function of alkylphosphate concentration. Measurements were performed in the presence and in the absence of lecithin. The enthalpy values measured upon addition of butanol to the mixtures were negative in all cases. Below the critical micelle concentration (CMC) of the alkylphosphates, the heats of butanol dissolution were found to decrease upon increasing the concentration of the alkylphosphate. This behaviour was related to the dissolution of butanol in water and to the formation of mixed butanol-alkylphosphate and butanol-alkylphosphate-lecithin micelles. Above the CMC essentially constant ΔH values were found. The ΔH measured may be the sum of simultaneous effects—heat of alcohol dissolution and the simple alkylphosphate micelle dissociation or alkylphosphate-lecithin mixed aggregate dissociation and the heat of mixed micelle formation. The ΔH at the plateaus were linearly related to the corresponding CMC values of the alkylphosphates.
The effect of a nutritional model of chronic liver injury on the hepatic glucuronidation of morphine in rats
Authors: Callaghan Richard , Desmond Paul V , Masheord Maurice L 
Published: April 2011

Abstract
The effect of a choline-deficient diet on the hepatic glucuronidation of morphine was investigated using a rat perfused liver system. Rats fed a choline-deficient diet developed a fatty liver with minimal necrosis. Despite the morphological changes, neither hepatic extraction ratio (0·51 ± 0·02 incontrol; 0·45 ± 0·04 in the choline-deficient rats) nor intrinsic clearance (0·85 ± 0·05 in control; 0·77 ± 0·09 in choline-deficient rats) were affected by this injury model. This finding suggests that glucuronidation is relatively resistant to this chronic liver injury.
An α-adrenoceptor-mediated mechanism of hypoactivity induced by β-amyrin palmitate
Authors: Subarnas Anas , Tadano Takeshi , Kisara Kensuke , Ohizumi Yasushi 
Published: April 2011

Abstract
Inhibitory effects of β-amyrin palmitate in locomotor activity of mice were studied by combining this compound with α-adrenergic agonists or antagonists and a dopaminergic agonist. β-Amyrin palmitate (2·5, 5·0 and 10·0 mg kg−1, i.p.) decreased locomotor activity of mice in a dose-dependent manner. It enhanced hypoactivity of mice treated with clonidine (0·025 mg kg−1, i.p.) and antagonized hyperactivity produced by phenylephrine (40 μg, i.c.v.). The inhibitory action of β-amyrin palmitate was not affected by yohimbine (1·5 mg kg−1, i.p.), but was potentiated by prazosin (0·75 mg kg−1, i.p.). When combined with a dopaminergic agonist, apomorphine (2·0 mg kg−1, i.p.), β-amyrin palmitate (5·0 and 10·0 mg kg−1, i.p.) did not affect locomotor stimulation produced by apomorphine. These results suggest that β-amyrin palmitate might inhibit α1-adrenoceptors.
Rheology of Model Aerosol Suspensions
Authors: Sidhu B K , Washington C , Davis S S , Purewal T S 
Published: April 2011

Abstract
The rheological properties of model aerosol suspensions at phase fractions of less than 5% w/v (phase ratio of 0.05) were investigated. The rheological profiles of lactose in chloroform, lactose in trichlorofluoromethane (Propellent 11, P11), and salbutamol sulphate in P11 have been investigated in the presence and absence of lecithin, a phospholipid surface-active agent. The relative viscosities of these disperse systems correlated with the increasing disperse phase fractions and the addition of surfactant was found to reduce these viscosities to a relative viscosity of aproximately 1·0. The results suggest that the relative viscosity is a useful indicator of flocculation in these systems, and may be valuable in formulation development.