bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dosage uniformity in hydrocortisone ointment B.P
Authors: Orr N A , Hill E A , Smith J F 
Published: April 2011

Abstract
The content uniformity of hydrocortisone in seven commercially available brands of hydrocortisone ointment B.P. 1% has been investigated. Fifty 5 mg samples were assayed by high pressure liquid chromatography and the results indicated that for 95% confidence levels only two of the ointments exhibited no positive skewness, one exhibited a significant degree of positive skewness and four exhibited a highly significant degree of positive skewness. The extent of the skewed distributions is discussed in relation to previously published particle/ agglomerate distributions for these ointments. The content uniformity in terms of the coefficient of variation CE calculated from the h.p.l.c. data is compared with the coefficient of variation CP that can be predicted from mixing theory on the basis of the particle/agglomerate distribution of the hydrocortisone. The departure from normality in drug content uniformity in the ointment is attributed to the hydrocortisone particles not being individually available for randomization, a large number being in an agglomerated form. That is, the manufacturing process is failing to achieve the full potential of the formulation by dispersing all of the agglomerates. Theoretical and experimental models predict that percutaneous absorption of drug may be enhanced over areas, where agglomerates are located, possibly not only resulting in localized toxicity but increased systemic availability. Drug content variability in small samples (5 mg) of topical steroid formulations could also effect the degree of skin blanching response in Mackenzie-Stoughton type tests since 5 mg portions containing in excess of twice the labelled strength were found. Regulatory control of content uniformity should be considered for certain topical steroids if unintentional over-dosage on small discrete areas is to be avoided.
Four benzodiazepine radioimmunoassays are described, the most sensitive of which can detect sub-therapeutic levels of bromazepam, chlordiazepoxide, clobazam, demoxepam, desalkylflurazepam, desmethyldiazepam, diazepam, flunitrazepam, lorazepam, medazepam, nitrazepam, oxazepam, prazepam, temazepam and triazolam. The standard curve for diazepam has a concentration range of 0–2·5 ng ml The assay is particularly applicable to blood samples of forensic interest that may be haemolysed or decomposing. A 75 μI sample is required. The antiserum and [3 H]flunitrazepam used are commercially available
Authors: Robinson Katherine , Rutterford Mary G , Smith R N 
Published: April 2011

Abstract
Four benzodiazepine radioimmunoassays are described, the most sensitive of which can detect sub-therapeutic levels of bromazepam, chlordiazepoxide, clobazam, demoxepam, desalkylflurazepam, desmethyldiazepam, diazepam, flunitrazepam, lorazepam, medazepam, nitrazepam, oxazepam, prazepam, temazepam and triazolam. The standard curve for diazepam has a concentration range of 0–2·5 ng ml The assay is particularly applicable to blood samples of forensic interest that may be haemolysed or decomposing. A 75 μI sample is required. The antiserum and [3 H]flunitrazepam used are commercially available.
Rate constants for drug release from micellar solutions of non-ionic surfactants
Authors: Collett J H , Dickinson N A 
Published: April 2011

Abstract
The release of a weak acid from micellar solutions containing different concentrations of two structurally related non-ionic surfactants was estimated using a dynamic dialysis apparatus. In all cases the effect of the surfactant was to reduce the amount of weak acid transferred. The data have been subjected to compartmental analysis using non-linear regression analysis. Rate constants for exchange across the dialysis membrane were independent of surfactant concentration. As surfactant concentration increased the rate constants for transfer from the non-micellar region did not show a marked change.
Availability of tritium from non-aqueous solutions of [1,2-3H]methyltestosterone, administered orally to rats
Authors: James K C , Nicholls P J , Sanders L M 
Published: April 2011

Abstract
The solvent-water distribution coefficients of 17α-methyltestosterone have been determined in selected alkanes, alkanols and alkane-alkanol blends. The oral availability of tritium from solutions of [3 H]methyltestosterone in these solvents and blends was studied in rats by measuring radioactivity in plasma, faeces and urine. Disappearance of radioactivity from the gut and biliary recirculation of 3 H were also examined. Variation of the solvent led to marked changes in the absorption of radioactivity, suggesting a possible method of varying bioavailability from soft gelatin capsules. Neither distribution coefficients nor tritium concentrations changed significantly from one homologue to another, but there was a marked difference when the alkane series was compared with the alkanol series. Blends of octane and octanol, together with the pure solvents, provided a suitable spread of distribution coefficients and tritium concentrations, but no simple relationship could be established between the two properties.
Some factors influencing the metabolism of benzylamine by type A and B monoamine oxidase in rat heart and liver
Authors: Parkinson David , Lyles Geoffrey A , Browne Barbara J , Callingham Brian A 
Published: April 2011

Abstract
The ability of MAO-A and MAO-B to metabolize benzylamine in vitro has been investigated in mitochondrial preparations from rat liver and heart. Although under normal circumstances benzylamine appeared to be metabolized exclusively by MAO-B in the rat liver, a contribution by both MAO-A and a clorgyline-resistant enzyme component was revealed when the MAO-B activity was much reduced by pretreatment of the mitochondria with appropriate concentrations of deprenyl. These three enzyme activities also contributed to benzylamine deamination in rat heart mitochondria. However, binding studies with [3 H]pargyline, which provided an estimate of the respective concentrations of MAO-A and MAO-B active centres in heart mitochondria, indicated a ratio between MAO-A and MAO-B, markedly different from that shown by plots of inhibition of benzylamine metabolism by various concentrations of clorgyline. The interpretation of these clorgyline plots is discussed in terms of the kinetic constants of both MAO-A and MAO-B, and the relative amounts of each enzyme. It is proposed that although the turnover rate constant for benzylamine metabolism by MAO-A is much smaller than that shown by MAO-B, in those tissues containing a large ratio of MAO-A:MAO-B content, the metabolism of benzylamine by MAO-A can be detected.
The effect of the particle size of an inert additive on the surface roughness of a film-coated tablet
Authors: Rowe R C 
Published: April 2011

Abstract
The effect of the particle size of a model inert additive—a dolomite, commercially available in a wide range of grades with varying particle sizes—on the surface roughness of a coated tablet has been studied using a stylus surface roughness measuring instrument. With all grades with a maximum particle size below 10–15 μm there was only a marginal increase in roughness on the addition of the material at low concentrations with a marked increase at concentrations in excess of 20–30% v/v. With the largest particle size material (mean size 18 μm) there was a marked increase in surface roughness at low concentrations with a decrease at higher concentrations. The different trends were due to the influence of the inherent roughness of the tablet substrate used. The results illustrate the potential of this accurate, rapid, simple and non-destructive technique in the optimization of film formulations during product development.
Mechanism of smooth muscle relaxation by tiropramide
Authors: PLANA R R VIDAL Y , CIFARELLI A , SETNIKAR I 
Published: April 2011

Abstract
Experiments on rabbit isolated colon show that a carbachol-induced contraction is accompanied by a decrease in cAMP content of the smooth muscle. (±)-α-(Benzoylamino)-4-[2-(diethylamino)-ethoxy]-NN-di-propylbenzen-propanamid (tiropramide, CR 605), a new tyrosine derivative with antispastic properties, increases cAMP concentrations within the same dose range that produces smooth muscle relaxation with or without carbachol (0·1 μm). These effects are potentiated by 1 mM theophylline, a phosphodiesterase inhibitor. In a purified microsomal preparation from rabbit colon smooth muscle, corresponding to sarcoplasmic reticulum, tiropramide induced a dose-dependent increase Ca2+ binding in the presence of ATP and Mg2+. Tiropramide inhibited phosphodiesterase activity in rabbit colon homogenates in a range of doses about ten times that producing relaxation, cAMP content enhancement and increase Ca2+ binding to sarcoplasmic reticulum. The effects of tiropramide on the carbachol-stimulated rabbit colon in the presence of theophylline, indomethacin or PGE1 are more in agreement with an action of tiropramide as inhibitor of cAMP catabolism than as a result of a prostaglandin-mediated effect. These observations suggest that the smooth muscle relaxant activity of tiropramide arises from drug-induced increase of cAMP concentrations possibly because of inhibition of cAMP catabolism. This effect is accompanied by the binding to the sarcoplasmic reticulum of Ca2+, preventing its interaction with the contractile proteins of the smooth muscle. A direct effect of tiropramide-enhanced cAMP content on contractile proteins in the smooth muscle cannot be excluded.
On the mechanism of salicylate-induced hypothrombinaemia
Authors: PARK B K , LECK J B 
Published: April 2011

Abstract
The mechanism of salicylate-induced hypothrombinaemia has been investigated in the rabbit. Administration of methyl salicylate produced a significant decrease in prothrombin complex activity, in the activity of clotting factors II, VII and X but no significant change in factor V activity. Metabolic studies with [3H]vitamin K1 showed that salicylate increased the plasma concentration ratio of [3H]vitamin K1-epoxide: [3H]vitamin K1. The results are consistent with the concept that salicylate produces its anticoagulant effect, like the coumarin anticoagulants, by interruption of the physiologically important vitamin K1-epoxide cycle at the epoxide reductase.
Inhibition of prostaglandin biosynthesis by clidanac and related compounds: structural and conformational requirements for PG synthetase inhibition
Authors: TAMURA SHIGEO , KUZUNA SEIJI , KAWAI KIYOHISA 
Published: April 2011

Abstract
The inhibition of prostaglandin (PG) biosynthesis by clidanac (6-chloro-5-cyclohexyl-1-indancarboxylic acid, TAI-284), its metabolites and some analogues has been examined using various microsomal preparations as enzyme source. Clidanac and some analogues were among the most potent inhibitors. The (+)-isomer of clidanac was shown to be 1000 times more potent than the (−)-isomer in inhibiting PG synthetase activity. The cis-3′-hydroxyl metabolite which retains anti-inflammatory activity comparable to that of clidanac had much less inhibitory activity. Structure-activity studies with clidanac analogues showed that the position of halogen substitution in 1-indancarboxylic acid is of considerable significance for the conformational requirement for binding to the enzyme.
Immobility test: effects of 5-hydroxytryptaminergic drugs and role of catecholamines in the activity of some antidepressants
Authors: BORSINI F , BENDOTTI C , VELKOV V , RECH R , SAMANIN R 
Published: April 2011

Abstract
Fenfluramine and m-chlorophenylpiperazine, two drugs purported to enhance central 5-hydroxytryptaminergic transmission, and metergoline, a 5-HT antagonist, did not modify the duration of immobility induced in rats made to swim in a restricted space. Nomifensine, desipramine and amineptine, three antidepressants known to block neuronal catecholamine uptake, significantly reduced the duration of immobility. Penfluridol, a dopamine antagonist at central receptors, counteracted the effect of nomifensine and amineptine but not that of desipramine. Propranolol and phenoxybenzamine respectively reduced the effects of desipramine and nomifensine but did not modify amineptine's effect. Metergoline pretreatment did not counteract the effect of any drug. The results indicate that various antidepressants can reduce the duration of immobility in rats by activating dopaminergic and/or noradrenergic mechanisms in the brain. Either α- or β- noradrenergic receptors could contribute to the anti-immobility effects, depending on the drug used. The immobility test appears to be insensitive to drugs activating or reducing 5-HT-ergic mechanisms in the brain.
The measurement of phenol coefficients by flow microcalorimetry
Authors: BEEZER ANTHONY E , HUNTER WILLIAM H , STOREY DAVID E 
Published: April 2011

Abstract
Microcalorimetric bioassay procedures have been applied to the determination of phenol coefficients and dilution coefficients. The derived values are compared with those from a standard AOAC test procedure. The microcalorimetric results indicate close agreement with AOAC values, good reproducibility (±2%), rapidity (30 min per test), potential for automation and the determination of in-use dilutions of disinfectants.
Some emulsifying and suspending properties of a polysaccharide gum derived from Mucuna flagillepes, Papilionaceae
Authors: UDEALA O K , UWAGA U N 
Published: April 2011

Abstract
The emulsifying and suspending properties of a new polysaccharide gum derived from an edible bean, Mucuna flagillepes have been investigated. The stability of the emulsion prepared with the gum was compared with that of emulsions prepared with acacia or tragacanth. Sherman's equations for concentrated emulsions were applied to determine the rate of coalescence k, and changes in mean cube globule diameter. Suspensions of sulphdimidine or zinc oxide prepared with tragacanth gum were compared with those prepared with mucuna gum. The final sedimentation height, Hu for each suspension was predicted using a biexponential relationship in the sedimentation pattern. The indication is that mucuna gum can be usefully employed as both an emulsifying and a suspending agent.
The effect of punch tip geometry on powder movement during the tableting process
Authors: SIXSMITH DAVID , MCCLUSKEY DAVID 
Published: April 2011

Abstract
Axial and radial powder movements during the tableting process have been studied using punches with various tip geometries. Radial powder movement has been shown to occur. Alteration of punch tip geometry did affect both axial and radial powder movement, the extent being dependent on the relative curvature of the punch tip. Addition of lubricant decreased relative axial movement but had little effect on radial movement.
The effect of compression on the capillary microstructure of tablets
Authors: CARLI F , COLOMBO I , SIMIONI L , BIANCHINI R 
Published: April 2011

Abstract
The effect of compaction pressure on the capillary characteristics of compacts of a crystalline drug and of a pure polymer was studied by means of penetration and porosimetry measurements. Not only the constant but also the exponent m of the general penetration volume-time relationship V = Kmtm proved to be strongly dependent on the pressure: as the compaction pressure is increased, the value of m tends to decrease. The capillary penetration data also showed the development of a marked heterogeneity in the structure of the polymer compacts at the lower compaction pressures: at these pressures the surface layers showed a much lower penetrability than the inner core of the compacts, whereas at the higher pressures the structure of the compacts was homogeneous. Furthermore, on the basis of a generally used equation describing the powder consolidation process, it was possible to relate the most relevant variation of the kinetics of capillary penetration into the drug compacts to the deformation of the particles. It is concluded that the capillary penetration measurements can give useful information in the understanding of the behaviour of pharmaceutical powders under compression.
Human brain monoamine oxidase: one molecular entity-multiple binding sites?
Authors: SCHURR AVITAL , HO BENG T , SCHOOLAR JOSEPH C 
Published: April 2011

Abstract
Monoamine oxidase (MAO) of human brain cortex was partially characterized by using different substrates and inhibitors. Two Km values were calculated for each of the three substrates tested, i.e., phenethylamine (PEA), benzylamine (BA) and 5-hydroxtryptamine (5-HT). Clorgyline and 5-HT, both known as MAO-A occupants, were able to abolish the second (high) Km deamination of PEA. 5-HT, while non-competitively inhibiting the deamination of low BA concentrations, competitively inhibited the deamination of high concentrations of this type B substrate. The kinetics of 5-HT deamination showed positive cooperation which indicates the involvement of subunits in the enzyme structure. The ability of some phospholipids to change the enzyme behaviour was considered as indication that these molecules might play a role in determining the ratio between the so-called A and B types of MAO, and in the regulation of the enzyme's activity.
Stability of bovine insulin
Authors: FISHER BARRY V , PORTER PATRICIA B 
Published: April 2011

Abstract
A stability experiment on purified crystalline bovine insulin showed that it deteriorates at normal refrigeration temperature (5°C) and that storage at −20°C is necessary to ensure stability. Purified insulin degrades by two mechanisms: deamidation and polymerization. Immunochemical potency determinations alone are insufficient to determine the stability of insulin as they may be little affected by the chemical changes which occur on storage. The activation energy for the polymerization of insulin was found to be 66 kJ mol−1 and for deamidation 45 kJ mol−1. It is recommended that crystalline bovine insulin be stored at −20°C.
Non-ionic surfactants and gastric mucosal transport of paraquat
Authors: WALTERS K A , DUGARD P H , FLORENCE A T 
Published: April 2011

Abstract
The influence of a range of polyoxyethylated non-ionic surfactants upon the transport of [14C]-paraquat dichloride across rabbit isolated gastric mucosa was investigated. Paraquat was shown to cross the mucosal epithelium by passive diffusion. Certain members of the surfactant series enhanced transmucosal paraquat transfer at low surfactant concentration (e.g. 0·001%) but the occurrence and magnitude of this effect was not dependent in a simple manner upon surfactant structure or physicochemical properties. At micellar concentrations the increase in paraquat transport was greatest with those surfactants possessing both ethylene oxide chains of 10–20 units and alkyl chains longer than C7-C9. The most effective absorption promoter was found to be Brij 36T (C12E10). At micellar surfactant concentrations, the enhancement of paraquat transfer appeared, from histological evidence, to be related to the ability of the surfactants to solubilize membrane components and disrupt epithelial cells.
The pharmacokinetics of a new benzamide drug, clebopride, in the rat and the dog
Authors: SEGURA J , GARCÍA I , BORJA L , TARRÚS E , BAKKE O M 
Published: April 2011

Abstract
After intravenous, intramuscular and oral administration of clebopride in the rat and the dog its apparent volume of distribution is high (1·6–3·2 1 kg−1) and it has a longer biological half-life than metoclopramide in both species. High clearance values and concentrations of metabolites in plasma after oral administration indicate that the drug is subjected to an extensive first pass metabolism in the rat. Thus, clebopride administered orally gives relatively low concentrations in the systemic circulation in rats even though it is rapidly absorbed. The metabolic processes appear to become saturated at high doses which is reflected in dose-dependent kinetics. Linear kinetics were observed in the dog, although enterohepatic recycling could occur.
How β2-selective is the adrenoceptor antagonist drug, IPS 339?
Authors: O'DONNELL STELLA R , WALDUCK KARIN 
Published: April 2011

Abstract
Schild plots for the compound (t-butylamino-3-ol-2-propyl)oximino-9-fluorene (IPS 339) have been obtained on isolated intrinsic tone trachea and atria (rate) of guinea-pigs. α-Adrenoceptors and uptakes were inhibited. The Schild plots for IPS 339 on trachea (fenoterol as agonist) and on atria (noradrenaline as agonist) were not superimposed suggesting that IPS 339 was β2-selective. The slopes of the Schild plots obtained on intrinsic tone tracheal preparations (isoprenaline or fenoterol as agonist), although greater than 1·0, were not significantly different from that on atria (noradrenaline as agonist). From the average separation of these Schild plots on trachea and atria IPS 339 was assessed to be only 3·3 times more active on β2- than on β1-adrenoceptors. The experiments in the literature which showed a high β2-selectivity for IPS 339 (155 fold) were carried out on carbachol-contracted tracheal preparations (isoprenaline as agonist) and the Schild plot obtained had a very low slope which was quite different from that on atria. Therefore, the results illustrate how the quantitative estimate of the selectivity of a β-adrenoceptor antagonist can be misleading when Schild plots with different slopes are compared.
A hypertensive response to baclofen in the nucleus tractus solitarii in rats
Authors: PERSSON B 
Published: April 2011

Abstract
The hypertension and tachycardia after intraperitoneal administration of baclofen, 5 mg kg−1, to conscious rats was prevented by a midcollicular decerebration but not by a brain transection rostral to the hypothalamus. In conscious rats, local application of baclofen (50 ng) into the region of the nucleus tractus solitarii (NTS) caused a consistent pressor response while injections into the hypothalamus, n. fastiguus, nn. amygdala, nn. dorsalis raphe or n. locus coreuleus did not. The cardiovascular effects of NTS injections of baclofen in anaesthetized animals were variable. The reflex heart rate reduction to noradrenaline (0·5 μg i.v.) was prevented by administration of baclofen i.v. as well as locally into the NTS. It is concluded that baclofen causes elevation of blood pressure in the NTS, and that this structure is a possible locus of action for systemically administered baclofen in producing hypertension.
Withdrawal syndrome after continuous infusion of clonidine in the normotensive rat
Authors: THOOLEN M J M C , TIMMERMANS P B M W M , VAN ZWIETEN P A 
Published: April 2011

Abstract
The effects on heart rate and arterial pressure of continuous subcutaneous infusion of clonidine (500 μg kg−1 day−1) via an ALZET miniosmopump and sudden termination of this treatment were studied in conscious normotensive rats. No consistent decreases of heart rate and blood pressure were observed during the clonidine infusion. Within a few hours following removal of the minipumps, a pronounced and long-lasting tachycardia developed. Mean arterial pressure did not exceed control level consistently, but transient blood pressure ‘upswings' were observed. The withdrawal phenomena were accompanied by a small, significant rise in plasma noradrenaline content. During the clonidine-infusion period piloerection and sedation were prominent. The present study indicates, that the occurrence of the withdrawal phenomena following cessation of clonidine treatment is not dependent upon a decrease of blood pressure and heart rate preceding clonidine withdrawal. Furthermore, the model presented may be suitable for the study of withdrawal phenomena of other antihypertensive drugs.