bluuebunny/crossref_metadata_2025_split huggingface dataset:
The metabolism of dibenzylamine: identification of NN-dibenzylhydroxylamine as the major in vitro metabolic product from rabbit fortified hepatic homogenates
Authors: Beckett A H , Coutts R T , Gibson G G 
Published: April 2011

Abstract
A study of the in vitro metabolism of dibenzylamine with fortified rabbit liver 9000 g supernatant fractions has shown that N-oxidation is the major metabolic process. Of the total amount of dibenzylamine metabolized, 90% is converted to NN-dibenzylhydroxylamine. The primary amine, benzylamine, is formed to the extent of only 6% of total substrate metabolized. The identity of the major metabolite, NN-dibenzylhydroxylamine has been established by thin-layer chromatography, gas-liquid chromatography and combined gas-liquid chromatography-mass spectrometry.
The interaction of antihistamines with lecithin monolayers
Authors: Attwood D , Udeala O K 
Published: April 2011

Abstract
The interaction of a series of antihistamines with monolayers of l-α-dipalmitoyl lecithin has been examined. An increase in the monolayer surface pressure was noted for monolayers spread on the antihistamine solutions, suggesting penetration of the film by drug molecules. At high surface pressures there was an apparent ejection of drug molecules from the film. The ability of the antihistamines to increase surface pressure was correlated with their surface activity at the air-solution interface. The effect of drug concentration on the magnitude of the surface pressure was examined for diphenhydramine hydrochloride. Application of the Gibbs adsorption equation at low surface compressions indicated an approximate area per molecule for diphenhydramine in the film which was in good agreement with the value previously obtained at the air-solution interface. Preliminary measurements showed that the surface pressure increase was larger in the presence of phosphate buffer at pH 6·8. It was not clear whether this effect was caused by the buffer components or was a pH effect.
Phenylbutazone-warfarin interaction in the dog
Authors: Bachmann K A , Burkman A M 
Published: April 2011

Abstract
The administration of phenylbutazone together with warfarin to dogs resulted in an elevation of the free fraction of warfarin in the plasma from 2·6 to 8·0% thus providing direct support for the notion that phenylbutazone induced inhibition of warfarin binding to plasma proteins. This inhibition as evaluated by a kinetic method was accompanied by a two-fold decrease in the plasma half-life of warfarin from 18·4 h in control animals to 9·6 h in phenylbutazone-treated animals. Marked increases in warfarin-induced hypoprothrombinaemia were observed when at doses up to 8 mg kg−1 (orally) it was given with phenylbutazone (50 mg kg−1, orally). The unbound fraction of warfarin in canine plasma ranged from 1·7 to 4·3% indicating individual differences in the extent of the plasma binding of warfarin in the dog.
The effect of pancuronium on myocardial contraction and catecholamine metabolism
Authors: Ivankovich A D , Miletich D J , Albrecht R F , Zahed B 
Published: April 2011

Abstract
The effects of pancuronium bromide infusion on the uptake and release of [14C] noradrenaline (14C-NA) by the isolated, perfused rat heart and on the chronotropic and inotropic activity of the isolated heart were evaluated. Hearts were removed from animals under light ether anaesthesia, transferred to a modified Langendorff perfusing apparatus and perfused with Krebs-Ringer bicarbonate solution at a rate of 5 ml min−1. The effect of pancuronium on the uptake of noradrenaline was determined by perfusing hearts for 5 min with perfusate containing various concentrations of pancuronium and 200 ng ml−1 of 14C-NA. After 5 min pancuronium-treated hearts contained less 14C-NA. The degree of reduced uptake increased with increasing concentrations of pancuronium. In addition, the combination of pancuronium perfusion and electrical stimulation (15 mA for 10 ms at 4 Hz) blocked the 50 min uptake of 14C-NA by the heart to a greater degree than either factor separately. The release of noradrenaline was determined after perfusing hearts with 14C-NA followed by perfusion with solution containing pancuronium but no 14C-NA for 1 h. Pancuronium infusion did not significantly alter the release of 14C-NA from the heart after 1 h of perfusion. The infusion of pancuronium caused a reduction in both the rate and strength of myocardial contraction of the isolated heart which was reversed by perfusion with perfusate free of pancuronium. Following perfusion with pancurnium the rate and strength of contraction of the heart was seen to “rebound” above pre-pancuronium values for a short period. The rebound of myocardial rate and contraction may have been due to the presence of myocardial noradrenaline previously blocked from reuptake by pancuronium since hearts removed from reserpinized animals did not demonstrate “rebound.”
Cornea preparation for in vitro biopharmaceutical evaluation of ophthalmic dosage forms
Authors: Barrelet J , Tsacopoulos M , Buri P 
Published: April 2011

Abstract
A system has been developed for a specific biopharmaceutical purpose: testing, for ophthalmic preparations, the influence of formulation on drug transport through the cornea. The apparatus is a lucite cell, divided in two compartments by a clamped rabbit cornea. Physiological conditions are ensured by a supply of oxygenated perfusion medium. They are monitored by electrical conductivity and corneal thickness measurements. Reliability of the system was tested in a set of experiments.
Comparison of the nuclear magnetic resonance and infrared spectroscopic methods for the quantitative analysis of polydimethylsiloxane
Authors: O’Neill I K , Pringuer M A , Prosser H J 
Published: April 2011

Abstract
A method based on nuclear magnetic resonance spectroscopy is described for the quantitative determination of polydimethylsiloxane (PMS) in a variety of pharmaceutical preparations. An extraction procedure using deuterochloroform within the sample tube was devised. In the presence of an internal standard, the PMS concentration was determined directly using integrated peak areas, without the necessity of establishing calibration curves. Accurate quantitative results were achieved with samples containing at least 2mg PMS, extracted from formulations containing greater than 0.5% PMS. The extraction procedure and nmr assay were both more efficient and convenient than the B.P.C. method.
The role of dopamine and noradrenaline in temperature control of normal and reserpine-pretreated mice
Authors: Cox B , Tha S J 
Published: April 2011

Abstract
Drugs with the common property of stimulating dopamine receptors, have been tested for their effects on core temperature in control and reserpine-pretreated mice. Apomorphine, amantadine, amphetamine, L-dopa and atropine all produced a fall in mouse oesophageal temperature, their efficacy correlating with their ability to activate central dopamine receptors. Amphetamine and L-dopa had a biphasic effect the initial fall being followed by a rise. In reserpine-pretreated mice only amphetamine, apomorphine, L-dopa and D,L-threo-dihydroxyphenyl-serine effectively reversed the hypothermia. Amphetamine had the highest efficacy of all the drugs tested. The sum of the effects of apomorphine and D,L-threo-dihydroxyphenyl-serine was equivalent to the effect of amphetamine alone. It is suggested that in control mice dopaminergic mechanisms mediate the hypothermia and noradrenergic mechanisms the hyperthermia. In reserpine-pretreated mice both systems are involved in the mechanisms restoring body temperature to normal.
Release of adrenaline by anaphylaxis in the guinea-pig: its effect on lung lipid content
Authors: Goadby P 
Published: April 2011

Abstract
The study was undertaken to discover whether the catecholamines released as a result of the stress and hypoxia of anaphylaxis were responsible for the concomitant loss of lipid from the lung. A method is described whereby the respiratory rate and volume and heart-rate of conscious sensitized guinea-pigs were measured and the electrocardiogram recorded during anaphylaxis induced by aerosolized antigen. After 7 days or more, some animals were anaesthetized with pentobarbitone and respiration was artificially maintained at the level recorded in the conscious state, whilst the quantity of catecholamines liberated during anaphylaxis was assayed using an extracorporeal blood circulation to superfuse smooth muscle preparations. In other animals of the same group, it was shown that intravenous infusion of adrenaline in a similar quantity to that detected in the circulation following anaphylaxis (0.3 μg min−1 for 40 min) caused losses of triglyceride and partial glycerides from the lungs. Thus, the loss of choline-containing phospholipid was attributed to the direct effects of the anaphylactic reaction on the lung tissue.
The effect of some polyene macrolides on absorption from the small intestine in the rat
Authors: English J , Chakraborty J , Marks V 
Published: April 2011

Abstract
The effect of three polyene macrolides, candicidin, amphotericin B and nystatin on the absorption of [3H]cholesterol was studied in the rat by using the in situ gut loop perfusion technique. Chronic treatment with candicidin and its presence at various concentrations in the gut loop perfusion experiments inhibited [3H]cholesterol absorption although a smaller effect was also obtained with amphotericin B and nystatin at higher concentrations. A similar but much less pronounced action of candicidin was also observed on the absorption of [3H]corticosterone and [14C]phenytoin.
The influence of casting solvent composition on structure and permeability of acrylic-methacrylic ester copolymer films
Authors: Abdel-Aziz S A M , Anderson W 
Published: April 2011

Abstract
Decrease in the solvation of polymer by inclusion of ethanol in the acetone casting solution resulted in greater permeability to urea of cast acrylate-methacrylate film. The greater permeability was accompanied particularly by a decrease in pore size and increase in pore number, despite the absence of change in pore area. A decrease in cohesiveness in the film was suggested by the decrease in tortuosity of the pores as seen by scanning electron microscopy; also, water uptake was increased when the film was cast from an ethanolic solution. The results support the view that, in practice, the composition of the solvent, by its effect on microstructure, can affect the function of the film cast from it.
A simple technique for the frequent intravenous infusion of fluid without heparin into the rabbit
Authors: Bowyer D E , Reidy M A 
Published: April 2011

Abstract
A technique is described for the daily intravenous injection over 16 weeks in the rabbit. The system consists of a Teflon cannula passed down the external jugular vein with the tip in the superior vena cava. The cannula is joined at the point of entry to the jugular vein to a length of silicon rubber tubing, which is then passed subcutaneously to the forehead. The silicon tubing is terminated on a Luer needle hub, which is held in a simple Perspex plate secured subcutaneously between the rabbit's ears. The Luer hub is covered with a replaceable rubber cap through which injections may be made. With this system cannulae were maintained patent for 16 weeks by flushing once a day with Hanks' balanced salt solution, pH 7·4.
Reversed ester analogues of pethidine: isomeric 4-acetoxy-1,2,6-trimethyl-4-phenyrpiperidines
Authors: Casy A F , Coates J E , Rostron C 
Published: April 2011

Abstract
The preparation and stereochemical characterization of all three isomeric forms of 4-acetoxy-1,2,6-trimethyl-4-phenylpiperidine is described. Of these, only the t-2-Me,c-6-Me,r-4-OCOMe isomer was an effective analgesic in mice (2·3 × pethidine) as judged by the hot-plate test. The results, together with reported data, demonstrate the potency raising effects of axial methyl α- to nitrogen and the lowering action of equatorial α-methyl substituents in reversed esters of pethidine.
Gastrointestinal absorption of carbenoxolone in the rat determined in vitro and in situ: deviations from the pH-partition hypothesis
Authors: Bridges J W , Houston J B , Humphrey M J , Lindup W E , Parke D V , Shillingford J S , Upshall D G 
Published: April 2011

Abstract
The absorption of [14C] carbenoxolone from everted rat ileum in vitro and from rat stomach and ileum in situ has been examined. The rate of its mucosal to serosal transfer in vitro increases as pH increases from 5 to 8 whereas the amount bound to ileum tissue decreases with increased pH; absorption closely parallels the drug's solubility. The uptake of carbenoxolone in situ is bi-exponential and the rate constants for the two processes, have been calculated. Absorption in situ, and biliary excretion, of the drug increases with increasing pH from 5·0 to 7·4. Tissue binding to the ileum in situ is not dependent on pH except below pH 5·0 when extensive tissue accumulation of carbenoxolone occurs because of its low solubility. Tissue binding to the stomach increases markedly with decrease of pH from 7·4 to 6·5 and at pH 6·5 is 80 times greater than binding to the intestine. The rate of absorption from the stomach, at pH 6·5–7·4, was much less than that from the intestine in situ. When allowance is made for the binding of carbenoxolone to the stomach, contrary to the pH-partition hypothesis, correlation is apparent between its absorption and the amount present in the ionized form.
Some pharmacological properties of the venom, venom fractions and pure toxin of the yellow-bellied sea snake Pelamis platurus
Authors: Tu Tsuchih , Tu Anthony T , Lin Tzu-Shen 
Published: April 2011

Abstract
The effects of the crude venom, four partially purified venom fractions and pure toxin (Pelamis toxin a) from yellow-bellied sea snake, Pelamis platurus, on respiration, blood pressure, heart and skeletal muscle of rabbits have been examined. Results indicated that crude venom, a partially purified toxic fraction and Pelamis toxin a caused initial respiratory stimulant effects followed by respiratory paralysis. In most cases, respiratory paralysis occurred before a profound fall in arterial pressure. Depression of the twitch response to nerve stimulation was observed in the tibialis anterior muscle. No significant change in the electrocardiogram was seen. Three partially purified non-toxic fractions of the crude venom induced transient respiratory stimulant effects. It was concluded that the crude venom and Pelamis toxin a had an identical mode of action and that they caused respiratory paralysis in rabbits.
Oxytetracyline tablet formulations: effect of variations in binder concentration and volume on granule and tablet properties
Authors: Chalmers A A , Elworthy P H 
Published: April 2011

Abstract
Formulation studies have been conducted on an oxytetracycline dihydrate tablet formulation containing microcrystalline cellulose and alginic acid, wet granulated with polyvinylpyrrolidone (PVP) solution. A range of granule properties including size, strength, packing and porosity, and tablet properties including breaking load, porosity, disintegration and dissolution have been measured. Increased compaction pressure decreased tablet porosity. The reproducibility of the above properties was determined by tests on nine standard batches of granules and tablets. An increased concentration of PVP in the binder solution decreased the rate of tablet dissolution. Although the volume of granulating solution apparently controlled the granule size, it did not significantly alter the tablet dissolution, when the amount of PVP was constant.
The crystallization behaviour of sulphathiazole
Authors: Jordan D , Carless J E 
Published: April 2011

Abstract
Previous investigations into the dissolution kinetics of sulphathiazole Form 1 have shown the process to be first order with respect to driving force. However, below 37° first order kinetics did not apply, due to the surface reaction becoming the rate controlling factor. The present study examines the kinetics of crystallization over the temperature range 25 to 50°. Crystallization is a process greatly dependent upon the high-entropy surface integration step which, unlike the dissolution process, is much more sensitive to crystal growth inhibitors. In the absence of inhibitors crystallization above 34° follows first order kinetics but below 34° the process changes to third order. Similar temperature effects on the dissolution of sulphathiazole have been previously reported.
Acute anti-inflammatory effects of aspirin and dexamethasone in rats deprived of endogenous prostaglandin precursors
Authors: Bonta I L , Bult H , Vincent J E , Zijlstra F J 
Published: April 2011

Abstract
Paw oedema, induced by carrageenan, was potentiated in normal rats by arachidonic acid and bishomo-γ-linoleic acid, but not by 5,8,11-eicosatrienoic acid. The latter is not an endogenous prostaglandin precursor, but replaces the other two in essential fatty acid deficient (EFAD) rats. Carrageenan oedema was partially suppressed in these EFAD rats. Aspirin exhibited equal suppression of carrageenan oedema in both normal and EFAD rats, despite the fact that, in the latter, prostaglandins are of negligible importance. The anti-inflammatory effect of dexamethasone was also identical in both normal and EFAD rats. The view that interference with the prostaglandin-system explains the acute anti-inflammatory effects of the two drugs, is discussed, in relation to the present results.
The effect of compression on some physical properties of microcrystalline cellulose powders
Authors: Sixsmith David 
Published: April 2011

Abstract
Tablets have been prepared from previously characterized microcrystalline cellulose (Avicel) powders, using an instrumented single station tablet machine. The regenerated particle size was found to increase with increase in compaction pressure. Compaction caused a slight initial decrease in B.E.T. surface area, followed by an increase mainly as a result of elastic recovery of the particles. The intra-particulate pore size distribution showed no change throughout the range of compaction pressures studied, demonstrating that the internal pores did not collapse. Measurement of the interparticulate porosity by mercury porosimetry, liquid penetration techniques and scanning electron microscopy showed a decrease in this parameter with increase in compaction pressure. The dissolution behaviour from the compacts showed in general a decreased rate with increase in compaction pressure, that from the cellulose grade PH 105 being slower than from the remaining grades.
Dimensional changes of compacts after compression
Authors: York P , Baily E D 
Published: April 2011

Abstract
A non-contact optical technique has been used to measure changes in the heights and diameters of compacts prepared from sodium chloride, spray dried lactose, two samples of methylcellulose powder and two spray-dried lactose-maize starch granulations. Both sodium chloride and spray dried lactose exhibited relatively small dimensional changes whilst the methylcellulose powders showed up to 30% axial and 3% radial expansion. The results are discussed in terms of the inherent properties of the materials. When the lactose was granulated with maize starch, the ratio of axial: radial strain recovery was reduced from 5·9:1 to approximately 1:1, suggesting an improved distribution of forces during compression of the granulations.
The influence of temperature on the sorption of benzocaine by nylon 6 from aqueous cosolvents
Authors: Richardson N E , Meakin B J 
Published: April 2011

Abstract
The influence of temperature on the sorption of benzocaine by nylon 6 powder from aqueous cosolvents has been assessed. At about 30° discontinuities appear in the Van't Hoff plots for sorption from water and aqueous PEG 400, which may be attributed to transitional changes in the polymer structure. No such discontinuities are apparent for sorption from aqueous ethanol over the temperature range 15–60°, which is indicative of plasticization by this cosolvent.
The fate of prostaglandin A1-5,6-3H in the rat
Authors: Sinha A J Wickrema , Shaw S R 
Published: April 2011

Abstract
The plasma concentrations, tissue distribution and excretion of prostaglandin A1 (PGA1) and related metabolites have been determined in rats, following the intravenous injection of a single dose of PGA1-5,6-3H. Urinary and faecal excretion accounted for averages of 25 and 43%, of the administered dose of PGA1, respectively. Oxidative cleavage of the carboxyl side chain of PGA1 appeared to be a major metabolic pathway in the rat. PGA1-5,6-3H was deemed unsuitable for metabolism studies in man, in view of the significant loss of tritium label from the prostaglandin.
The effect of some binding agents on the mechanical properties of granules and their compression characteristics
Authors: Doelker E , Shotton E 
Published: April 2011

Abstract
The modulus of elasticity and the crushing strength of cylindrical granules prepared by a template method, and the friability of conventional granules were measured and the effect of the binding agents, PVP, methyl cellulose and maize starch examined. These properties were related to the compression characteristics of the granules and to the crushing force of the subsequent tablets. According to the base material two cases were observed. With dicalcium phosphate little plastic flow was evident and low radial stress transmission was noticed, the softest granules led to the weakest compacts. With paracetamol more plastic flow occurred giving a greater axial to radial conversion of force and the softest granules produced the strongest tablets. The extent of further generated contact area played the major role. Generally, due to the better bonding capacity, dicalcium phosphate gave stronger compacts than paracetamol, although lower radial transmission ratios were recorded. A good conversion of axial to radial force was thus proved not to be the main factor in obtaining good tablets, as was also confirmed by the paracetamol powder alone. With paracetamol the residual pressure on the die wall was greater with the formulations producing satisfactory tablets than with paracetamol alone which gave rise to capping.
Derivatization to stabilize some aliphatic primary hydroxylamines for g.l.c. analysis
Authors: Beckett A H , Achari R 
Published: April 2011

Abstract
By appropriate choice of trimethylsilylating and trifluoroacetylating reagents and organic solvents for extraction, stable derivatives of aliphatic primary hydroxylamines metabolites, N-hydroxyphentermine, N-hydroxychlorphentermine, N-hydroxymexiletene, N-hydroxy-phenethylamine, N-hydroxyamphetamine, and N-hydroxy-3,4-dimethoxyamphetamine, were obtained and examined by g.l.c. analysis without decomposition and without interference from the parent drug or other metabolic products.
The enkephalins and opiates: structure-activity relations
Authors: Horn Alan S , Rodgers John R 
Published: April 2011

Abstract
The X-ray structures of 9 ‘opiate’ drugs which exhibit a range of pharmacological activity have been examined in detail leading to the theory that one of the reasons why the enkephalins and related peptides possess morphine-like activity is because they have a tyrosine, and hence a ‘tyramine’, residue at the amino terminal position. This residue or a conformationally similar moiety, can be shown to be present in many opiates and analogues.
The effects of etilefrine on blood vessels in the rat tail
Authors: Frost B R , Frewin D B , Gerke D C 
Published: April 2011

Abstract
Etilefrine was found to constrict blood vessels in the rat tail through a mechanism which was partly dependent on the sympathetic nerves present in these vessels. The response to the drug was enhanced by pretreatment with noradrenaline and cocaine, and totally abolished by the α-receptor antagonist phentolamine. When compared with several other sympathomimetic agents which were tested on the vessel, etilefrine appeared to have a low order of vasoconstrictor activity. These findings would seem to have considerable relevance to the clinical situation where an attempt has been made to use etilefrine in the treatment of patients with orthostatic hypotension.