bluuebunny/crossref_metadata_2025_split huggingface dataset:
The antifibrillatory potency of aprindine, mexiletine, tocainide and lignocaine compared on Langendorff-perfused hearts of rabbits and guinea-pigs
Authors: Almotrefi Abdulrahman A , Baker J B E 
Published: April 2011

Abstract
The effectiveness of three new antiarrhythmic drugs, aprindine, mexiletine and tocainide in elevating ventricular fibrillation threshold measured in the Langendorff-perfused rabbit heart and in protecting against ouabain-induced arrhythmias in the Langendorff-perfused guinea- pig heart has been compared with that of lignocaine. All these drugs have produced a significant rise in the threshold but quantitatively mexiletine was about equal to, tocainide five times less and aprindine thirty-eight times more potent than lignocaine in this effect. Aprindine differed from the other three drugs in that it had a slow onset of action and its effect was not entirely removed upon reperfusion with the drug-free solution. Only aprindine and mexiletine provided complete protection against ouabain-induced ventricular fibrillation while 3 of 6 and 4 of 6 hearts fibrillated in the presence of lignocaine or tocainide respectively.
In vitro actions of NN-dimethyl-2-aminoindane and related compounds
Authors: Little Hilary J , Rees J M H 
Published: April 2011

Abstract
The actions of 2-aminoindane, 2-amino-1,2,3,4-tetrahydronaphthalene and amphetamine and their N-methyl and NN-dimethyl derivatives on the guinea-pig ileum were compared. All, except the tertiary 2-aminoindane, inhibited the responses to electrical stimulation and it is suggested that this is not fully explained by their sympathomimetic properties. NN- Dimethyl-2-aminoindane increased these responses and caused contractions of the unstimulated ileum due to a nicotine-like action. The indane series was more effective in producing contractions of the ileum than the other compounds. The three tertiary derivatives antagonized competitively the actions of histamine on the ileum and those of 5-hydroxytryptamine on the rat uterus.
Influence of the sterilization method and of magnesium oxide on the tissue responses in the rat to modified starch glove powders
Authors: Pelling D , Butterworth K R 
Published: April 2011

Abstract
The tissue response to samples of a surgical glove powder was assessed from counts of the adhesions and granulomas found 7 and 14 days after introduction into the peritoneal cavity of rats, and by a histological study of affected tissues. Negative control groups treated with no powder and positive controls treated with talc were included. Various sample treatments were implemented to examine the effect of the sterilization method on the tissue response and the influence of magnesium oxide, normally added as a dispersing agent. The glove powder produced less reaction when steam-sterilized than when γ-irradiated and the presence of magnesium oxide at 2% concentration made no detectable difference.
Quantitative structure-activity relationships: the Van't Hoff heats of transfer of resorcinol monoethers from water to n-octanol
Authors: Beezer Anthony E , Hunter William H , Storey David E 
Published: April 2011

Abstract
The partition coefficients of resorcinol and some resorcinol monoalkyl-ethers from water to n-octanol have been measured as a function of temperature. These data are used to evaluate ΔG, ΔH and ΔS for the solute transfer process. The data suggest direct calorimetric measurement of these parameters should be performed. Correlation with calori-metrically determined ‘biological response’ will permit a more detailed and precise commentary upon the quantitative structure-activity relationships for these compounds.
The assay of pseudoephedrine hydrochloride in tablets and liquid formulations by two phase acid-base titration
Authors: Jones R , Marnham G 
Published: April 2011

Abstract
A novel titration method for the assay of pseudoephedrine hydrochloride in formulations is presented. Pseudoephedrine base is extracted into chloroform and titrated with acid in a two phase system. The method is specific for the drug in tablet and syrup formulations. The precision and speed of assay are comparable with existing spectrometric and titration methods for amine drugs.
Age-dependent differences in the effect of phenprocoumon on the vitamin K1-epoxide cycle in rats
Authors: Trenk Dietmar , Beermann Dieter , Oesch Franz , Jähnchen Eberhard 
Published: April 2011

Abstract
The anticoagulant activity and the pharmacokinetics of phenprocoumon as well as the effect of phenprocoumon on the vitamin K1-epoxide cycle in younger (12 weeks) and older (36 weeks) male inbred Lewis rats has been examined in a study of the mechanism responsible for the increase in the responsiveness to oral anticoagulant drugs (OAD's) with increasing age. After a single i.v.-dose of phenprocoumon (0†355 mg kg−1 the anticoagulant effect obtained was greater in older than in younger rats. There were no differences between younger and older rats in the rate of elimination, volume of distribution and in the free fraction and free concentration values of phenprocoumon in plasma and liver. After i.v.- injection of 64·3 μg kg−1 [3 H]vitamin K1 and different doses of phenprocoumon (0·02 to 3 mg kg−1) the [3 H]vitamin K1 concentration in the liver decreased and the [3 H] vitamin K1-2, 3-epoxide concentration increased dependent on the dose and the liver concentration of phenprocoumon. These changes were more pronounced in the older than in the younger rats. Concentration-response curves gave similar EC50-values for both age-groups but a 1·6-fold higher maximal response (expressed as vitamin K1-epoxide/vitamin K1 ratios) in the older rats. Since OAD's exert their anticoagulant effect most probably by inhibiting an enzyme (vitamin K1-epoxide reductase) which regenerates vitamin K1 from the epoxide metabolite and since the vitamin K1-epoxide/vitamin K1 ratios in the liver may reflect the degree of inhibition of the epoxide reductase by OAD's, our results may indicate that the inhibitory effect of phenprocoumon on this enzyme is more pronounced in older than in younger rats. This could explain the age-dependent differences in the anticoagulant activity.
On the importance of agonist concentration-gradients within isolated tissues. Increased maximal responses of rat vasa deferentia to (–)-noradrenaline after blockade of neuronal uptake
Authors: Kenakin Terry P 
Published: April 2011

Abstract
It is assumed often that blockade of agonist uptake processes in isolated tissues results only in shifts to the left of the concentration-response curves to the agonist with no concomitant increase in the maximal response. This may not be true in tissues where diffusion is not fast enough to permit penetration of the agonist to a sufficient number of muscle cells for production of tissue maximal response. Under these circumstances an agonist-concentration gradient is created within the tissue which, when altered, could lead to an increase in the maximal response to the agonist. The increased maximal responses of rat vasa deferentia to (–)-noradrenaline after blockade of neuronal uptake by either cocaine or desmethylimi-pramine have been analysed in terms of a concentration-gradient hypothesis. The data are compared with a theoretical calculation based on a model of restricted diffusion of enzymesubstrates into structured tissues. Both the experimental data and theoretical calculations suggest that an altered concentration-gradient of (–)-noradrenaline within the muscle layers of rat vasa deferentia is responsible for the increased maximal response. The effects of such gradients are discussed in terms of quantitation of drug-receptor phenomena and as a caveat to ascribing increases in maximal responses to post-synaptic effects of uptake inhibitors.
Factors affecting the release and excretion of dopamine in the rat
Authors: Akpaffiong M J , Redfern P H , Woodward B 
Published: April 2011

Abstract
The effects of inorganic salts and of diuretic agents on the excretion of dopamine (DA) were examined in the rat. Both types of treatment evoked significant increases in urinary DA excretion, urine volume and urinary sodium excretion. In the salt-treated animals a significant correlation was observed between DA excretion and urine volume, whereas after diuretic treatment there was better correlation between DA and urinary sodium excretion. The salt- treated animals showed a high correlation between administered chloride and DA excretion. Subcutaneous administration of DA produced a significant diuresis and an increase in sodium excretion. The mechanisms responsible for these responses are discussed with reference to the possibility that DA has a physiological role in the kidney.
Analysis of factors affecting the mean sizes of granules produced from ternary mixtures of powders
Authors: JAIYEOBA K T , SPRING M S 
Published: April 2011

Abstract
Multiple linear regression analysis has been used to relate the mean sizes of granules prepared from ternary mixtures of powders to such physical properties as particle size, solubility and wettability and to processing variables such as the amount of binder and the proportions of the different components. The major influences on granule size were the amount of binder and the affinity of the third component for the binder liquids.
Some solute-solvent complexes involving testosterone and testosterone propionate
Authors: JAMES K C , MEHDIZADEH M 
Published: April 2011

Abstract
Solute-solvent interactions have been studied by observing the influences of carbon tetrachloride, carbon disulphide, ethyl oleate, isopropyl myristate and octanol on the solubilities of testosterone and testosterone propionate in an inert solvent (cyclohexane). Complexation with testosterone was detected, but there was no evidence of complexation between testosterone propionate and these solvents. The solvent-induced infrared shifts were due to non-specific solvent effects. The existence of solute-solvent complexes between the two solutes and chloroform, previously detected by infrared absorption, was confirmed. The solubility technique, which has previously only been used with solid complexing agents, is adaptable to liquid complexing agents, but has limitations.
Evaluation and comparison of colorimetric, radiometric and high performance liquid chromatographic assays for aminopyrine-N-demethylation by rat liver microsomes
Authors: BAST A , NOORDHOEK J 
Published: April 2011

Abstract
Aminopyrine (DMAP) is metabolized by two successive N-demethylations to monomethyl-4-aminoantipyrine (MMAP) and 4-aminoantipyrine (AAP). Separation and quantification of DMAP and its metabolites in microsomal incubation mixtures by h.p.l.c. showed that other reactions also occur. In the radiometric method where [Me2-14C] DMAP is used as substrate, [14C]formaldehyde is formed during the N-demethylation. However since commercial [14C]DMAP, is not completely double labelled, and both MMAP and AAP are formed, it is impossible to calculate the formaldehyde formation accurately from the specific activity of [14C]DMAP. Moreover, it was shown that DMAP, AAP and particularly MMAP may all develop considerable colour intensity with the Nash reagent, which is used to determine formaldehyde. Despite this difficulty, DMAP may still be used as a model substrate in vitro, with the Nash assay being used to determine formaldehyde if low substrate concentrations and a short incubation time are used. Thus the interference of DMAP or its metabolites with the Nash assay is negligible. As the same Km and Vmax values were obtained from both the radiometric and the relatively precise colorimetric assay it is suggested that there is little wrong with either method, at least under our experimental conditions. The h.p.l.c. method however, underestimates formaldehyde formation, probably because metabolites other than MMAP and AAP are formed. The latter method however may be used to analyse the aminopyrine metabolism in more detail.
Evaluation of a prototype micro-electronic autoclave cycle integrator
Authors: KIRK B , HAMBLETON R 
Published: April 2011

Abstract
Instability and non-uniformity of spore preparations and the non-conformity of chemical indicators to the temperature coefficients of spore inactivation are problems associated with current methods of autoclave cycle monitoring. A prototype micro-electronic instrument, which largely overcomes these problems, is described. It monitors autoclave cycles in terms of the integral F0 and Nabla functions. Its thermometric and integrating accuracy is demonstrated. A discussion of the problems associated with the use of sensitive electronic instruments in the autoclave room environment reveals the need for independent monitoring areas when such devices are used. Inactivation constants were determined for spores of the organism Bacillus stearothermophilus, NCTC 10 003 and were described using D115 (12.0 min) and Z (9.0 °C) values and the first order reaction Arrhenius constants A (1041, 2 min−1) and Ea (74.4 kcal mol−1, 311 kJ mol−1). These have been compared with recently published values. The standardization of F0 and Nabla is discussed with reference to the setting of minimum values related to product bioburden and maximum values related to an acceptable degree of product degradation.
The mechanism of interaction between chlorhexidine digluconate and poly(2-hydroxyethyl methacrylate)
Authors: PLAUT B S , DAVIES D J G , MEAKIN B J , RICHARDSON N E 
Published: April 2011

Abstract
The extent of the interaction between chlorhexidine digluconate and poly(2-hydroxyethyl methacrylate), (PHEMA), is independent of temperature between 22–50 °C which is consistent with an ion-ion interaction mechanism. Different contact lens materials exhibit different affinities for chlorhexidine digluconate, the extent of uptake correlating in rank order with the number of free carboxylic acid sites in the polymers. Esterification of the carboxyl groups with diazomethane, resulted in a reduction in the affinity of the treated polymers for chlorhexidine to a near basal level. The uptake of chlorhexidine in soaking solution experiments involving lenses made from PHEMA and the more ionic material, poly(2-hydroxyethyl methacrylate - co-isobutyl methacrylate - co - methacrylic acid), was consistent with their carboxylate content. However, the fraction of bound disinfectant released was lower from the terpolymer, suggesting there are differences in bonding strengths between chlorhexidine and different contact lens hydrogels.
Two metabolites of sulphinpyrazone and their identification and determination by mass spectrometry
Authors: JAKOBSEN P , PEDERSEN A KIRSTEIN 
Published: April 2011

Abstract
Sulphinpyrazone is an antiplatelet agent in vivo and in vitro. Two active metabolites, a sulphide (S) and a hydroxylated sulphide (S-OH) have been identified in rabbit and human plasma and a selective and sensitive g.c.-m.s.-method for quantitative determination of the sulphide and hydroxylated sulphide in plasma and urine has been evolved which allows concentrations down to 5 ng ml−1 for the sulphide and 30 ng ml−1 for the hydroxylated sulphide to be detected. The time course of the metabolite concentrations in plasma corresponds to the biological findings, suggesting that the metabolites contribute significantly to the in vivo effects of the drug.
A metabolic and pharmacokinetic comparison of theophylline and aminophylline (theophylline ethylenediamine)
Authors: MONKS T J , SMITH R L , CALDWELL J 
Published: April 2011

Abstract
The metabolism and pharmacokinetics of intravenously administered theophylline and aminophylline (theophylline ethylenediamine) have been studied in 3 volunteers, using 14C-labelled theophylline. Both compounds were metabolized extensively and 1, 3-dimethyl-uric acid, 1-methyluric acid, 3-methylxanthine and two unknown minor metabolites were excreted in the urine, in addition to theophylline. The elimination of theophylline, 1, 3-dimethyluric acid, 1-methyluric acid and the unknown metabolites followed first-order kinetics, but that of 3-methylxanthine followed Michaelis-Menten kinetics. When given as aminophylline, theophylline was metabolized more rapidly and extensively than when given alone. The recovery of 14C in the urine was significantly higher after aminophylline than after theophylline. Abstention from intake of dietary methylxanthines for 7 days resulted in more rapid and extensive metabolism of aminophylline compared with results from the same subjects on their usual diets. The results indicate that, from a metabolic and pharmacokinetic viewpoint, aminophylline and theophylline are not equivalent.
Effect of pH on the micellar properties of amphiphilic drugs in aqueous solution
Authors: ATTWOOD D , NATARAJAN R 
Published: April 2011

Abstract
The influence of pH on the micellar properties of several amphiphilic drugs under conditions of constant ionic strength has been investigated. No significant effect of pH on the critical micelle concentration or micellar size of chlorpromazine hydrochloride was noted over a pH range well below the pKa. The micellar properties of opipramol, thiopropazate, flupenthixol, clopenthixol, and trifluoperazine, which contain a piperazine moiety showed considerable pH dependence. The concentration dependence of the pKa in these micellar systems was taken into consideration in the selection of pH values representative of complete protonation of either one or both of the piperazine N atoms. A lower aggregation number and higher critical micelle concentration was observed at a low pH corresponding to complete protonation of both charge centres. Mepyramine maleate exhibited a non-micellar mode of association at pH 5·5 which could be described by a stepwise association model in which association constants, KN, increased sequentially with aggregation number, N, according to the relationship, KN = K(N − 1)/N where K = 31·3 dm3 mol−1. No significant association could be detected at pH 2 when the pyridine ring N was fully protonated.
Effects of structural variations of non-ionic surfactants on micellar properties and solubilization: surfactants containing very long hydrocarbon chains
Authors: ARNARSON THORDIS , ELWORTHY P H 
Published: April 2011

Abstract
Polyoxyethylene mono-ethers of dotriacontanol (C32E41) and 4, 9-dimethyltritriacontanol (C35E40) have been synthesized. The micellar weights in water at 298K were 4·82 × 105 and 5·90 × 105, the aggregation numbers 212 and 260, and the levels of hydration 290 and 283 mol water mol−1 surfactant, respectively. The solubilization of azobenzene, cortisone acetate, griseofulvin, sulphadiazine, phenylbutazone, betamethasone, tolbutamide, and menaphthone was studied in 2% solutions of the above surfactants. The presence of large micelles did not result in increased solubilization; C32E41 and C35E40 had a lower solubilizing capacity than that of cetomacrogol.
A theoretical conformational study of substituted o-anisamides as models of a class of dopamine antagonists
Authors: PANNATIER A , ANKER L , TESTA B , CARRUPT P A 
Published: April 2011

Abstract
The quantum mechanical PCILO method has been used to investigate the conformational behaviour of N-(2-aminoethyl)- and N-(2-dimethylaminoethyl)-o-anisamide, two model molecules of substituted benzamides. The molecules are shown to have only limited conformational freedom due to the presence of two intramolecular hydrogen bonds acting as conformational locks. The molecules in their preferred conformation are characterized by a distance between the centre of the aromatic ring and the nitrogen atom of almost 6 Å, i.e. almost 1 Å longer than in the fully extended dopamine conformers. Some implications at the receptor level of this topographical dissimilarity are discussed.
Actions of dopamine and apomorphine on the vasoconstrictor responses of perfused mesenteric arteries of mouse, rat and rabbit
Authors: ANWAR N , MASON D F J 
Published: April 2011

Abstract
Dopamine (10−7-10−6 m) and apomorphine (5 × 10−7 − 5 × 10−6 m) inhibited the vasoconstrictor responses of the perfused mesenteric artery preparations of rat, rabbit and mouse to adrenergic nerve stimulation but did not affect responses to added noradrenaline. The inhibitory effects of both dopamine and apomorphine were prevented by haloperidol (3 × 10−7 m) but not by yohimbine (3 × 10−8 m) in rat and rabbit mesenteric artery preparations. In contrast, yohimbine (3 × 10−8 m), but not haloperidol, antagonized the inhibitory effect of dopamine and apomorphine in mouse mesenteric artery preparations. In higher concentrations, dopamine (10−6 − 10−4 m) produced a direct vascoconstrictor effect, which involved post-junctional α-adrenoceptors in all three species. However, in preparations contracted with 10−7 m 5-hydroxytryptamine and in the presence of phentolamine (3 × 10−7 m) and propranolol (10−6 m), dopamine (10−6 − 10−4 m) produced a direct relaxant effect in rabbit mesenteric artery preparations but not in those of rat and mouse. It is suggested that inhibition of neurogenic vasoconstrictor responses, by dopamine and apomorphine, may be mediated through a specific prejunctional inhibitory dopamine receptor in the mesenteric artery of rat and rabbit whereas in the mouse they involve activation of α-adrenoceptors.
An analysis of the mechanism of 5-hydroxytrypt-amine-induced vasopressor responses in ganglion-blocked anaesthetized dogs
Authors: FENIUK W , HARE J , HUMPHREY P P A 
Published: April 2011

Abstract
5-Hydroxytryptamine (5-HT) administered intravenously (i.v., 1–30 μg kg−1) to ganglion-blocked anaesthetized dogs produced dose-related increases in diastolic blood pressure and we have analysed the mechanism involved. Cyproheptadine and methysergide (10–100 μg kg−1 i.v.) were potent and specific antagonists of the 5-HT induced rise in blood pressure, while the α-adrenoceptor blocking agent phentolamine (0·3–3 mg kg−1 i.v.) also caused dose-related inhibition. Syrosingopine pretreatment converted the vasopressor action of 5-HT to a vasodepressor action and acute bilateral adrenalectomy caused a marked reduction in the 5-HT-induced rise in blood pressure. In two dogs, 5-HT (30 μg kg−1 i.v.) markedly increased the venous plasma concentrations of noradrenaline and adrenaline. We concluded that the 5-HT-induced rise in diastolic pressure in the ganglion blocked anaesthetized dog is due largely to the release of catecholamines of which a substantial component is from the adrenal gland. The rise in diastolic blood pressure is specifically blocked by low doses of cyproheptadine and methysergide suggesting that the release of catecholamines is mediated by specific 5-HT receptors located mainly within the adrenal medulla.
Animal modelling of human polymorphic drug oxidation—the metabolism of debrisoquine and phenacetin in rat inbred strains
Authors: AL-DABBAGH S G , IDLE J R , SMITH R L 
Published: April 2011

Abstract
The metabolism of debrisoquine (5mg kg−1 orally) was investigated in females of 7 strains of rat. Two major metabolic pathways, those of 4- and 6- hydroxylation were found to be polymorphic. The DA strain eliminated in urine only 7–10% of the dose as 4-hydroxy-debrisoquine together with 31–55% debrisoquine while the corresponding values for the Lewis strain were 44–55% and 11–17% respectively. Accordingly, DA and Lewis rats were proposed as models for the human PM (poor metabolizer) and EM (extensive metabolizer) drug oxidation phenotypes. To further test this model, DA and Lewis rats were given phenacetin (200 mg kg−1 orally). This underwent O-de-ethylation to paracetamol (52–55%) and aromatic 2-hydroxylation (7–8%) in Lewis rats. The corresponding findings in DA rats were 35–40% O-de-ethylation and 12–13% 2-hydroxylation. It is suggested that, with respect to both debrisoquine and phenacetin, Lewis and DA inbred rat strains afford a model of oxidative drug metabolism for the human EM and PM phenotypes respectively.