bluuebunny/crossref_metadata_2025_split huggingface dataset:
The vascular changes after ephedrine tachyphylaxis
Authors: Morishita H , Furukawa T 
Published: April 2011

Abstract
The changes elicited after ephedrine tachyphylaxis in the dog femoral and rabbit aortic strips isolated from the untreated and ephedrine pre-treated animals have been studied. In untreated strips, ephedrine exhibited dose-dependent contractions which were blocked by phenoxybenzamine. These contractile responses to ephedrine were reduced after pre-treatment with ephedrine in vivo. In rabbit aortic strips previously contracted with noradrenaline or KCl, ephedrine induced dose-dependent relaxations at high concentrations, which were not affected by propranolol. These relaxation responses were likewise diminished after ephedrine. Dose-related contractile responses to noradrenaline were potentiated at low concentrations and depressed at high concentrations after ephedrine whereas those to adrenaline were inhibited over the entire agonist range. Responses to KCl were not affected. These reductions in the responses to noradrenaline and adrenaline after treatment with ephedrine in vivo were inhibited by increased calcium2+ concentration. From the results, it can be presumed that the observed changes in vascular responsiveness may be partially involved in the development of ephedrine tachyphylaxis.
An investigation into the deposition of inhalation aerosol particles as a function of air flow rate in a modified ‘Kirk Lung’
Authors: Davies P J , Hanlon G W , Molyneux A J 
Published: April 2011

Abstract
The effect of air flow rate on the deposition of inhalation aerosol particles in a modified ‘Kirk Lung’ has been studied. Two commerical products were used. The amount depositied in the mouthpiece and throat regions decreases with increasing flow rate. The amount in the collector rises to maximum of approximately 50%. This material represents the therapeutically available portion. Such an apparatus would be useful for routine quality control of the size distribution ratios for inhalation aerosol particles.
The in vitro dissolution of phenobarbitone sodium from ethyl cellulose microcapsules
Authors: Jalsenjak I , Nicolaidou Constantia F , Nixon J R 
Published: April 2011

Abstract
Microcapsules of sodium phenobarbitone, with a wall of ethyl cellulose, have been prepared. The size distribution was determined by use of standard sieves and the effect of core: wall ratio noted. Release of the drug into an aqueous medium was studied. The release pattern was found to have similar characteristics to the release of a drug from an insoluble porous matrix.
Factors affecting the binding of tricyclic tranquillizers and antidepressants to human serum albumin
Authors: Sharples D 
Published: April 2011

Abstract
The linear free energy-related model for structure activity relations developed by Hansch & Fujita (1964) has been used to correlate the binding of tricyclic tranquillizers and antidepressants to human serum albumin (HSA) with hydrophobic and electronic parameters. The parameters chosen being the chromatographic parameter (Rm) and the affinity of charge transfer complex formation (kc). The relative importance of these factors has been assessed by linear and multiple linear regression analysis. Results show that the major factor in binding is electronic with only a minor contribution from the hydrophobic parameter.
Effects of phosvitin on the ecg changes induced under hypoxia in the rat
Authors: Caprino L , Falchetti R , Borrelli F 
Published: April 2011

Abstract
The effect of phosvitin (1 g kg−1, i.p.) on ecg changes induced in rats by a reduction of partial oxygen pressure in the respiratory mixture was studied. Phosphocreatine, phosphoserine, ATP and Na2HPO4.2H2O were also administered intraperitoneally for comparison. Phosvitin alone was found to prevent the hypoxia-induced T-wave changes (flattening or disappearance), which were also temporarily aggravated by injection of noradrenaline. As to the metabolic, hypoxia-induced myocardial changes, two hypotheses are discussed: a release of phosvitin phosphate radicals ready for immediate utilization or a drug action mediated via a membrane-bound intrinsic proteinkinase system.
The effect of propranolol on sympathetic nerve stimulation in isolated vasa deferentia
Authors: Hughes I E , Kneen Barbara 
Published: April 2011

Abstract
(±)-Propranolol hydrochloride (0·5 mg kg−1 twice daily, subcutaneously, for 3 days or approximately 2·4 mg kg−1 daily, orally, for 21 days) failed to produce ptosis or to affect responses to transmural stimulation of isolated vasa deferentia removed from treated mice. In guinea-pig isolated vasa deferentia responses to transmural stimulation through parallel electrodes were reduced by propranolol (1 to 20 μg ml−1); blockade was concentration dependent, fast to equilibrium (45 min), easily reversed by washing but not reversed by (+)-amphetamine sulphate (0·2 μg ml−1). At lower concentrations (0·04 and 0·2 μg ml−1), propranolol marginally potentiated responses to transmural stimulation. In contrast, guanethidine (0·2 μg ml−1) produced a slow onset blockade which was completely reversed by (+)-amphetamine. The response to electrical stimulation through concentric ring electrodes was reduced by low concentrations of propranolol but this effect is ascribed to the known local anaesthetic actions of propranolol and no evidence of true adrenergic neuron blockade was found.
Oxytetracycline tablet formulations: the influence of excipients and the method of granulation
Authors: Chalmers A A , Elworthy P H 
Published: April 2011

Abstract
The proportion of microcrystalline cellulose and alginic acid present as excipients in the dry mix for an oxytetracycline dihydrate tablet formulation, prepared by a conventional wet granulation process, has been shown to influence granule formation and properties. Granule size distributions have varied widely due perhaps to variation in binder distribution. Granulating with water was equally satisfactory to granulating with a PVP solution. Slugged granules produced robust tablets, which disintegrated and dissolved rapidly.
Aggregation of antiacetylcholme drugs in aqueous solution: micellar properties of some diphenylmethane derivatives
Authors: Attwood D 
Published: April 2011

Abstract
Light scattering methods have been used to examine the aggregation in aqueous solution of a series of antiacetylcholine drugs based on the diphenylmethane nucleus. The drugs investigated included adiphenine hydrochloride, piperidolate hydrochloride, benztropine mesylate, orphenadrine hydrochloride, chlorphenoxamine hydrochloride, lachesine hydrochloride, poldine methylsulphate, pipenzolate bromide, clidinium bromide, benzilonium bromide and ambutonium bromide. A micellar pattern of association was established for all compounds and critical micellar concentrations and aggregation numbers have been determined.
Anomalies in some properties of powder mixtures
Authors: Varthalis S , Pilpel N 
Published: April 2011

Abstract
Mixtures of lactose and paracetamol and of lactose and oxytetracycline exhibit anomalous properties. The mean particle sizes, tensile strengths and flow properties of the mixtures are not proportionally intermediate between those of the constituents. The results are ascribed to changes that occur in the packing arrangements of the particles. These changes could have practical consequences in monitoring the progress of a mixing operation by measuring apparent particle size and in controlling the properties of granules, capsules and tablets prepared from the mixtures.
Effect of polymer cation content on certain film properties
Authors: OKOR R S 
Published: April 2011

Abstract
Mixing of two acrylate-methacrylate copolymers designated A and B and differing only in cation (quaternary ammonium) content in the ratio 2:1 (A:B) provided a means of varying polymer cation content in resulting films. Film permeability to the permeant urea, increased with increase in cation content; a two phase change characterized by a slow increase at a low cation content level followed by about 13 times more rapid increase at a high cation content level. The point of transition from the slow to the rapid phase was 53 moles cation per mole polymer chain. On average a 2 fold increase in cation content resulted in a 500 fold increase in permeation rate. Increases in film swelling and pore size also accompanied the increase in cation content, but the change in permeability was more positively correlated with the corresponding change in film pore size. Mutual repulsion by charged groups during film formation is suggested as a factor promoting the formation of large pores in the film at high cation content.
Effects of structural variations of non-ionic surfactants on micellar properties and solubilization: variation of oxyethylene content on properties of C22 monoethers
Authors: ARNARSON THORDIS , ELWORTHY P H 
Published: April 2011

Abstract
Studies on erucyl alcohol ethoxylated with 40 and 47 units, and on behenyl alcohol ethoxylated with 33 and 43 units, gave values of 106, 101, 271, and 304 (all × 103) for the micellar weight, 51, 42, 152, and 137 for the aggregation numbers, and 257, 362, 209, and 311 moles water mol−1 surfactant for the micellar hydration, respectively. Measurements of the solubilization of azobenzene, cortisone acetate, griseofulvin, sulphadiazine, phenylbutazone, betamethasone, tolbutamide, and menaphthone showed that the erucyl derivatives were better solubilizers than the behenyl compounds, and that solubilization increased as the polyoxyethylene chain was shortened; this change was more pronounced with the erucyl compounds.
Pathways of decomposition of propylbenzilylcholine mustard in neutral and alkaline solution
Authors: YOUNG J M 
Published: April 2011

Abstract
High-voltage electrophoresis has been used to follow the decomposition of propylbenzilylcholine mustard (PrBCM) in aqueous solution. Dilute solutions of PrBCM in 10 mM phosphate buffer, pH 7.5, or Krebs-Henseleit solution allowed to stand for 1 h at room temperature (22–24 °C) contain mainly the aziridinium ion derivative. At pH 7.5 the concentration of this ion declines slowly, giving rise first to the N-hydroxyethyl derivative and then ultimately, following hydrolysis of the ester bond, to NN-bis(2-hydroxyethyl)propylamine and benzilic acid. In contrast, in 5 mM NaOH the ester bond undergoes rapid hydrolysis, so that the major species present after 15 min at room temperature is the N-hydroxyethylaziridinium ion. This ion then undergoes slow reaction with hydroxyl ion to yield the same final decomposition product, NN-bis(2-hydroxyethyl)propylamine, as is observed at pH 7.5.
Volume of water-filled pores in the ethyl cellulose membrane and the permeability of microcapsules
Authors: VIDMAR VESNA , Jalšenjak I , KONDO T 
Published: April 2011

Abstract
The volume fraction of the water-filled pores in the microcapsule membranes was calculated and the values from 0.55 to 2.5% were obtained. Differential scanning calorimetry of aqueous suspensions of microcapsules showed no structured water present in the ethyl cellulose membranes. The temperature effect on the apparent diffusion coefficient of a drug was investigated and the apparent activation energy of diffusion was calculated.
An investigation of the relationship between particle size and compression during capsule filling with an instrumented mG2 simulator
Authors: JOLLIFFE I G , NEWTON J M 
Published: April 2011

Abstract
An instrumented mG2 capsule filling machine simulator has been employed to study the effects of the amount of compression (compression ratio) on the capsule fill weight uniformity and measured compression and ejection stresses. Four size fractions of lactose were studied (mean particle sizes 15.6, 17.8, 37.5 and 155.2 μm). The range of compression over which satisfactory filling could be achieved was large for fine, cohesive powders but decreased with increasing particle size. The lower limit of filling ability was the ability to retain the powder and the amount of compression needed to achieve retention increased with increasing particle size. The upper limit on compression, was the compaction of the powder which prevented the piston acting to cause retention. Large particle sizes were able to undergo only a small change in volume before compaction occurred whilst fine, cohesive powders were considerably more compressible and hence could be filled satisfactorily at higher compression settings.
Anti-warfarin antibody preparation and its characterization for radioimmunoassay
Authors: SATOH HIROKO , HAYASHI MASAHIKO , SATOH SUSUMU 
Published: April 2011

Abstract
Anti-warfarin antiserum was prepared in rabbits by immunization with a synthesized warfarin antigen, 4′-azo-warfarin human serum albumin, which possesses two enantiomorphic haptenic sites of warfarin on the molecule. The antiserum recognized both R- and S-warfarin to the same degree, 50% cross reactivities of racemic warfarin, respectively. One of the warfarin metabolites, racemic warfarin alcohol, showed 1% cross reactivity, and R- or S-warfarin alcohol have half the reactivity of the racemic alcohol. Rabbit plasma warfarin levels were determined by radioimmunoassay using this antiserum and racemic [14C]warfarin and by fluorometric assay after isolation by thin layer chromatography. After a single administration of warfarin (2 mg kg−1 orally or 500 μg kg−1 i.v.), the plasma levels determined by both assay methods showed a good correlation (r = 0.97, P &lt; 0.001, Y = 1.04–0.09). The results show that the radioimmunoassay can determine total plasma warfarin without interference of plasma metabolite. The applicability and limitation of the radioimmunoassay for pharmacokinetic study are discussed.
Cardiovascular effects in the rat of ketanserin, a novel 5-hydroxytryptamine receptor blocking agent
Authors: PERSSON BENGT , HEDNER THOMAS , HENNING MATTS 
Published: April 2011

Abstract
Following intravenous administration of ketanserin (0.3–10 mg kg−1) to conscious or anaesthetized normotensive and spontaneously hypertensive rats there were dose-dependent blood pressure reductions but no compensatory tachycardia. Intracerebroventricular administration of ketanserin (25–500 μg) had inconsistent and largely insignificant cardiovascular effects. In a dose range where it produces hypotension ketanserin antagonized the pressor responses to adrenaline and noradrenaline as well as to 5-hydroxytryptamine in monoamine depleted and spinalized rats. It is suggested that the hypotensive action of ketanserin in the rat does not involve a central mechanism but a peripheral α-adrenolytic action is implicated.
Demonstration of maximum solubilization in a polyoxyethylene alkyl ether series of non-ionic surfactants
Authors: ELWORTHY P H , PATEL M S 
Published: April 2011

Abstract
The solubilization of azobenzene, menaphthone, cortisone acetate, and griseofulvin was measured in a series of non-ionic surfactants of structure CH3[CH2](m−1) [OCH2CH2]1.25mOH, where m varied from 8 to 18. Maximum solubilization occurs when m = 16 (the hexadecyl alkyl ether). This is explained in terms of changes in the oxyethylene mantle close to the micelle core/mantle interface, which appears to be the main locus of solubilization. Micellar properties of CH3[CH2]17[OCH2CH2]22OH are also reported and discussed.
A study of enzyme and protein microencapsulation—some factors affecting the low apparent enzymic activity yields
Authors: WOOD D A , WHATELEY T L 
Published: April 2011

Abstract
Microencapsulation of aqueous solutions of enzymes, α-chymotrypsin (EC 3.4.21.1) and histidase (EC 4.3.1.3), with semipermeable polyamide membranes resulted in a loss of enzymic activity. The low yields (less than 40%) found with both enzymes were typical of others reported in the literature. The activity of broken histidase-containing microcapsules was greater than that of the microcapsules before breaking, and this was interpreted as being due to a simple diffusional restriction on the substrate and product. The maximum of the apparent pH-activity curve of α-chymotrypsin was found to be shifted one unit to more alkaline pH when the enzyme was encapsulated. This phenomenon was explained in terms of the hydrogen ion concentration in the microenvironment surrounding the enzyme being different from that in the bulk solution. Microencapsulation of aqueous solutions of enzymes is accomplished by in situ polymerization reactions at the interface of a water-in-oil emulsion. 125I-labelled proteins (albumin and fibrinogen) were encapsulated under similar conditions to determine the efficiency of the microencapsulation process. About one third of these proteins was lost during the overall preparation procedure and a further fraction was attached to the membranes of the microcapsules.
Nabumetone (BRL 14777, 4-[6-methoxy-2-naphthyl]-butan-2-one): a new anti-inflammatory agent
Authors: BOYLE E A , FREEMANM P C , MANGAN F R , THOMSON M J 
Published: April 2011

Abstract
Nabumetone is a compound of novel structure which displays acute anti-inflammatory activity in the carrageenan-induced oedema model in rats and the ultraviolet-induced erythema model in guinea-pigs. Its activity in these tests is greater than that of aspirin but less than that of naproxen and indomethacin. In the cotton pellet-induced granuloma model in the rat, the compound is active and produces no signs of toxicity at doses much greater than the lowest effective dose, unlike aspirin, naproxen or indomethacin. Nabumetone is also active in the adjuvant-induced arthritis test in rats. In contrast to aspirin, indomethacin and naproxen, the compound is well tolerated by the stomach of fasted rats at doses in excess of those with anti-inflammatory activity. These findings could be linked to the relatively poor ability of nabumetone to inhibit the synthesis of prostaglandins in vitro and to its non-acidic structure. The compound has greater mild analgesic activity than paracetamol, is equi-active with phenylbutazone, but less active than aspirin, naproxen and indomethacin. Nabumetone also has antipyretic activity in the rabbit. No interactions with the hypothalamic-pituitary-adrenal axis have been found.
The effect of a novel, non-steroidal anti-inflammatory compound, nabumetone (BRL 14777), on cellular infiltration into 24-hour polyvinyl sponge implants in the rat, compared with some steroidal and nonsteroidal anti-inflammatory drugs
Authors: BOYLE ELIZABETH A , MANGAN F R 
Published: April 2011

Abstract
The time-course of cell migration into saline-soaked sponge implants over 5 days showed peak polymorphonuclear leucocyte (PMNL) infiltration at 24 h. In common with the corticosteroids dexamethasone and hydrocortisone, and the non-steroidal anti-inflammatory drugs indomethacin, (+)-naproxen, BW 755C and benoxaprofen, nabumetone decreased cell migration into the sponges. PMNLs and mononuclear cells were reduced at 24 h, and there was a parallel decrease in exudate levels of the lysosomal acid hydrolase β-N-acetyl glucosaminidase [NAG ECB, 3, 2, 1, 30]. Impregnation of sponges with λ-carrageenan (1%) caused a 2–3 fold increase in cell numbers, with a relatively greater proportion of PMNLs; drug effects were more marked in these implants.
Particles in small volume injections
Authors: Taylor S A , Spence J 
Published: April 2011

Abstract
The level of particulate contamination in small volume injections has been examined using the light blockage (HIAC) and electrical sensing zone (Coulter counter) techniques, the HIAC system being found to be the more suitable. Particle counts on the same batch of injection showed a large and variable difference between the HIAC and the Coulter counter results, especially below 5 μm. None of the injections examined complied with the British Pharmacopoeia limits for particulates in large volume parenterals, suggesting the unsuitability of the limits for small volume parenterals.
The effects of BW755C and other anti-inflammatory drugs on eicosanoid concentrations and leukocyte accumulation in experimentally-induced acute inflammation
Authors: Salmon John A , Simmons Paula M , Moncada Salvador 
Published: April 2011

Abstract
BW755C (3-amino-1-[m-trifluoromethyl)phenyl]-2-pyrazoline HCl) reduced the concentration of leukotriene B4 (LTB4), thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) in exudate derived from the subcutaneous implantation in rats of 0˙5% carrageenanimpregnated polyester sponges. Polymorphonuclear leukocyte (PMN) migration into the inflammatory exudate was also decreased. The inhibition of LTB4 may, in part, account for the lower number of cells in the exudate since LTB4 is a potent leukotactic agent. Inhibition of LTB4-formation and cell migration by BW755C was dose-related, but the two dose-response curves were not parallel. Cell influx still occurred at doses of BW755C that completely inhibited formation of LTB4: this indicates that, although LTB4 may have a chemotactic role in-vivo, other factors must also contribute to cell migration into the inflammatory exudate. Treatment of rats with dexamethasone also caused a reduction in leukocytes and eicosanoids in the exudate. As with BW755C, there was a differential effect on PMN and LTB4: dexamethasone (1 mg kg−1) reduced PMN accumulation by 40% but LTB4 formation was inhibited by 70%. Leukocyte accumulation was also inhibited by the non-steroidal anti-inflammatory drugs (NSAID's), indomethacin and flurbiprofen. These drugs reduced the concentration of both PGE2 and TXB2 in exudate but that of LTB4 was unchanged. This suggests that reduction of PMN accumulation by indomethacin and flurbiprofen is mediated by a mechanism other than inhibition of LTB4-synthesis. Aspirin also reduced the levels of PGE2 and TXB2 in the exudate but did not consistently affect PMN influx, thereby confirming that inhibition of cyclo-oxygenase does not reduce cell migration in inflammation.
The effects of polymorphism, particle size and compression pressure on the dissolution rate of phenylbutazone tablets
Authors: Tuladhar M D , Carless J E , Summers M P 
Published: April 2011

Abstract
The dissolution rate of phenylbutazone from tablets after disintegration has been used to determine whether the drug particles underwent crushing or bonding during compression. Two polymorphic forms of the drug were used and the predominant effect for high drug concentration (60%), during compression was dependent upon the original particle size of the drug and its polymorphic form. With a low drug concentration (10%) in the tablet, the diluent protected the drug particles from bonding together. The particle size change of the drug during compression was affected by the nature of the diluent present. Lactose had an abrasive action on Form A phenylbutazone compared with Avicel but had little effect on the more ductile Form B. When the contact time of compression was decreased from 29 to 0·-26 s, the 6 μm particles of drug showed less bonding at the shorter time (faster rate of compression) but the effect observed with the larger particles was independent of the compression rate.
Determinants of systemic availability of promethazine in rabbits
Authors: Taylor G , Houston J B 
Published: April 2011

Abstract
Promethazine blood concentration-time curves have been determined in 7 rabbits following intravenous, oral and hepatic portal vein administration of promethazine. This phenothiazine has a large volume of distribution and a high metabolic clearance resulting in low blood concentrations particularly when the oral route is used. Analysis of the areas under the blood concentration-time curves indicates that hepatic first-pass metabolism is the major determinant of promethazine’s low oral availability. Absorption from the gastrointestinal tract is essentially complete in most rabbits and the contribution of metabolism by the intestinal mucosa is minimal. The present findings are compared with the literature on other phenothiazines.