bluuebunny/crossref_metadata_2025 huggingface dataset:
Viscosity of phosphatidylcholine (lecithin)
Authors: PERRIN J H , SAUNDERS L
Published: April 2011

The viscosities of egg lecithin dispersed in water have been measured by means of a Couette viscometer. The more concentrated dispersions are thixotropic, but below 1·8% w/w of lecithin the sols become Newtonian. From the extrapolated ratio of specific viscosity to volume fraction, the dispersed particles are considered to be of an elongated rod-like shape. When the coarse dispersions of lecithin are irradiated ultrasonically, an irreversible clearing of the sols occurs, accompanied by a big decrease in viscosity. None of the irradiated sols examined was thixotropic and the extrapolated viscosity ratio indicated a low asymmetry and degree of hydration for the dispersed particles. The effect of ultrasonic irradiation is not only to reduce size and asymmetry of the aggregates but also to expel water from them.
Further effects of imipramine and its desmethyl derivative on the hypothermia induced by reserpine
Authors: BERNARDI D , JORI A , MORSELLI P , VALZELLI L , GARATTINI S
Published: April 2011

Imipramine and desipramine injected intracerebrally increase the temperature of fully reserpinised rats. Desipramine is more effective than imipramine in this. The effect of imipramine seems to be independent of the formation of desipramine in the brain. That imipramine, injected intraperitoneally, leads to an accumulation of brain desipramine has been confirmed.
The rigidity of gelatin-glycerin gels
Authors: NIXON J R , GEORGAKOPOULOS P P , CARLESS J E
Published: April 2011

At 25° the presence of glycerin in gelatin gels increased the modulus of rigidity in all the samples used. An empirical relationship between rigidity and the concentrations of gelatin and glycerin was calculated which was valid within the range 4–15% gelatin and 0–40% glycerin. A critical concentration of gelatin was found at which neither Bloom number nor glycerin concentration affected the rigidity. No simple relationship was found between Bloom number and rigidity.
The pharmacology of 2-amino-4-methyl-6-phenyl-amino-1, 3, 5-triazine, a centrally acting muscle relaxant
Authors: BRITTAIN R T
Published: April 2011

2-Amino-4-methyl-6-phenylamino-1, 3, 5-triazine (CB.2487) was found to resemble mephenesin both qualitatively and quantitatively in its actions in mice, and could be distinguished from meprobamate and pentobarbitone. In this species CB.2487 antagonised strychnine competitively but had no effect against leptazol or nicotine. In the anaesthetised cat, the most pronounced action of CB.2487 was to block multi-synaptic crossed extensor and flexor reflexes in doses which did not suppress the mono-synaptic patellar reflex. The compound also depressed selectively the crossed extensor reflex and not the patellar reflex in the spinal animal. CB.2487 had no effect on the myoneural junction. The results indicate that CB.2487 is a centrally acting muscle relaxant. Unfortunately the drug was poorly active by mouth and had a short duration of action. It is considered to have no advantage over mephenesin.
A basic model for the evaluation and prediction of preservative action
Authors: GARRETT EDWARD R
Published: April 2011

basic integrated model for the quantification of preservative action must consider the availability or thermodynamic activity of the biologically effective concentration, μ, of the preservative in the aqueous phase. A derived expression for the total concentration, PT, of preservative (of dissociation constant Ka) degrading by an apparent first order rate constant, k', in an oil/water emulsion (of q volume ratio and k intrinsic partition coefficient of undissociated preservative) needed to maintain a minimum inhibitory concentration μ of free undissociated acid in the aqueous phase at any hydrogen ion concentration [H+] and for any known binding or complexing phenomena (where there are n sites on binding macromolecule Mi and the intrinsic dissociation constant is ki) is PT = μ (f1 × f2 × f3). The binding enhancement factor of μ is

and in many practical instances when μ < Ki it reduces to

The oil/water partition and ionization enhancement factor is f2 = 1 + Ka/[H+] + kq where kq vanishes in the absence of oil. The instability enhancement factor is f3 = ek't. The ultracentrifuge can be used to define operationally the parameters in macromolecular binding and the apparent partition in dispersions, emulsions and solutions. The premises for the use of preservative combinations are critically evaluated and kinetic methods to determine proper choices of response to characterise combined preservative action are recommended.
The effect of pH and temperature on the lysis of yeast cells by cationic dyes and surfactants
Authors: RIEMERSMA J C
Published: April 2011

Conductivity measurements in yeast suspensions, to which a stepwise increasing quantity of a cytolytic reagent was added, provided evidence towards explaining possible mechanisms of cytolysis by cationic dyes and by cationic surfactants. These lytic cations are bound to the cell surface. If uptake exceeds a critical amount, the permeability barrier of part of the yeast cells in the suspension is destroyed. The “threshold” amount of lytic agent was proportional to the quantity of yeast in the suspension, and was pH- and temperature dependent in a way which suggested an interaction with anionic membrane lipids. There were similarities between the cationic dyes, Toluidine Blue and Azure A, and the cationic surfactants, cetrimide and cetylpyridinium chloride, in their cytolytic effect on yeast cells. A mechanism of membrane breakdown is discussed.
Lowering of plasma triglycerides as a result of decreased free fatty acid mobilization
Authors: BIZZI A , VENERONI E , GARATTINI S
Published: April 2011

3, 5-Dimethylpyrazole and its metabolite 3-carboxy-5-methylpyrazole lower plasma FFA and decrease the level of plasma triglycerides. The metabolite given intravenously is more rapidly effective than 3, 5-dimethylpyrazole. Plasma cholesterol and phospholipids as well as blood glucose were not affected by these acute treatments.
The determination of fluocinolone acetonide in formulated products
Authors: BAILEY F , HOLBROOK A , MILLER R J
Published: April 2011

A chromatographic procedure for the determination of fluocinolone acetonide is described. The method employs a hexane: dioxan: water partition system supported on Celite. The progress of the chromatogram is followed by measurement of the ultraviolet absorption of eluate fractions at 238 mμ. The application of the method to the determination of fluocinolone acetonide in cream, ointment and lotion formulations is described.
The semi-quantitative assay of neamine and neomycin C in neomycin by thin-layer chromatography
Authors: VICKERS C
Published: April 2011

Thin-layer chromatographic methods are described for the separation and assay of neamine and neomycin C in neomycin sulphate and its preparations. The samples are chromatographed on binder-free silica gel plates using, as developing solvents, a 3·85% w/v ammonium acetate solution to separate neamine from the neomycins and a 3·4% w/v ammonium hydroxide solution to separate neomycin C from neomycin B and neamine. The spots are made visible by spraying with a 1% v/v solution of t-butyl hypochlorite in dichloroethane-acetic acid (9:1), removing the excess reagent in a stream of cold air and spraying with a 0·5% w/v solution of potassium iodide in 0·5% w/v starch mucilage. The size and intensity of the spots produced is compared with standards and the neamine or neomycin C content of the sample estimated. The results obtained for neomycin C are comparable with those given by chromatography on an ion-exchange resin. A possible explanation is offered for the lack of agreement in the case of neamine. The chromatographic systems described are also applied to paromomycin and shown to separate paromamine, paromomycin I and paromomycin II, not only from each other, but also from neamine and the neomycins.
A rapid method for the estimation of impurities in saccharin and sodium saccharin
Authors: KING R E , WRAGG J S
Published: April 2011

A procedure is described for the detection and estimation of o-toluenesulphonamide, saccharin-o-toluenesulphonylimide, toluene-2,4-disulphonamide, saccharin-4-sulphonamide, o-sulphamoylbenzoic acid, p-sulphamoylbenzoic acid and benzoic acid in saccharin and sodium saccharin using thin-layer chromatography on Kieselgel GF254. The solvent system used is chloroform-methanol-strong ammonia solution (100:50:11·5). Compounds containing a free sulphonamide group are detected by an “N-chloro” reaction, while the other compounds are detected by examining the chromatogram in ultraviolet light (253·7 mμ). Impurities in commercial saccharin and sodium saccharin are estimated by comparison on the chromatogram with standards containing purified saccharin or sodium saccharin and suitable amounts of the impurities.
Freeze-dried preparations of Penicillium spinulosum
Authors: BOYD IAN , BULLOCK KENNETH
Published: April 2011

BY a freeze-drying process powders have been obtained containing mould spores in even distribution. These are suitable for use in studying the survival of such spores in the dry state under various environmental conditions, including the presence of fungicidal agents. The preparation of such powders by the more difficult and less easily controlled process of spray-drying has been described by Brown & Bullock (1960).
The stimulation of strychnine metabolism in rats by some anticonvulsant compounds
Authors: HOWES J F , HUNTER W H
Published: April 2011

The metabolism of a series of 4-acetyl-1-naphthyl ethers has been examined in rats and in fractions of rat liver homogenate. The administration of the compounds to rats increases the rate of strychnine metabolism when the compounds used are metabolised by the microsomal fraction of liver homogenate.
The evaluation of a molecular sieve technique to determine the interaction between a preservative and a surfactant
Authors: ASHWORTH R W , HEARD D D
Published: April 2011

The interaction between methyl p-hydroxybenzoate and polysorbate 80 has been determined using a molecular sieve technique. At 25° and at surfactant concentrations of 2·86 and 1·43% respectively, the ratios of total to free preservative were 2·9 and 1·9. These results are comparable with published data.
Effect of chlorhexidine upon 32P release and cell viability in Escherichia coli
Authors: RYE R M , WISEMAN DAVID
Published: April 2011

The amount of the cold trichloroacetic acid soluble fraction (metabolic pool), expressed as a percentage of its 32P content, released from labelled cells of Escherichia coli treated with chlorhexidine has been compared with the percentage of cells killed by the chlorhexidine. Treatment was with amounts varying from 0–64 μg/ml for 5 min at 20°. Approximately 100% of the cells were killed and 100% of the metabolic pool released by treatment with 64μg/ml of chlorhexidine. At 4, 8 and 16 μg/ml the percentage of cells killed by chlorhexidine is significantly lower than the percentage of the metabolic pool released.
Screening for tertiary and quaternary alkaloids in some African Fagara species
Authors: CALDERWOOD J M , FISH F
Published: April 2011

A method has been described for the separate extraction of tertiary and quaternary alkaloids from plant material. Different thin-layer chromatographic systems have been used to separate compounds within each group of alkaloids. The methods have been applied to the screening of the barks of five Fagara species in which the presence of angoline, angolinine, skimmianine and, in some cases, 1-hydroxy-2,9,10-trimethoxy-NN-dimethylaporphinium chloride is indicated.
Phytochemical investigations of some species of Colchicum
Authors: FELL K R , RAMSDEN DOREEN
Published: April 2011

A colorimetric assay for colchicine and its congeners has been devised. It is based on the yellow colour produced by the treatment of these alkaloids with mineral acid and is useful over the range 0·0005–0·0025% w/v. Together with the method of Pesez (1957) it has been used to assay extracts of species of Colchicum and the individual alkaloids were identified by paper chromatography. It was concluded that C. tunicatum, a native of Israel, contained sufficient colchicine to make it a useful source of this alkaloid.
Micro-colorimetric determination of cholinesterase activity of motor end plates in the rat diaphragm
Authors: BUCKLEY G A , NOWELL P T
Published: April 2011

A spectrophotometric method is described for the determination of total cholinesterase activity in groups of 3–30 end plates, after staining with copper thiocholine and dissecting from the rat diaphragm, by continuous recording of the yellow colour (412 mμ) produced by reaction between dithiobisnitrobenzoate (1mm) and thiol groups liberated enzymatically from acetylthiocholine (5mm) at pH 7·0. Cholinesterase activity of end plates after correction for muscle ranged from 3·3–22·3 times 10−11m/end plate/hr and muscle cholinesterase activity ranged from 8·8–29·4 times 10−11 μg/hr. 2·9–26·7% of measured end plate cholinesterase activity was attributable to muscle. The results for end plate cholinesterase agreed with those obtained by other workers using microgasometric techniques. It was calculated that there were approximately 3·6 times 106 cholinesterase active sites/end plate which compared closely with 6 times 106 molecules acetylcholine released/ nerve ending/impulse and 2·6 times 106 cholinergic receptors/end plate given in the literature. It is suggested that each acetylcholine molecule after liberation from a nerve ending may interact with one receptor and be destroyed by one cholinesterase active site.
The influence of the female sex hormones on the response of the pig uterus to electrical stimulation
Authors: KNIFTON A
Published: April 2011

The response of the pig myometrium to electrical stimulation in vitro was used to assess the influence of the female sex hormones at different stages of the oestrus cycle. Optimal stimulation produced greater tension in the mature uterus than in the immature uterus and the tension was greater in the oestrogen-dominated uterus than in the progesterone-dominated uterus. The minimum (threshold) voltage necessary to elicit an isometric contraction was not influenced by the stage of the uterus in the oestrus cycle. Varying the frequency of stimulation caused changes in tension indicating the predominant sex hormone. The progesterone-dominated myometrium appears to bind calcium more strongly than the oestrogen-dominated myometrium.
The compaction properties of sodium chloride in the presence of moisture
Authors: SHOTTON E , REES J E
Published: April 2011

The effect of moisture on the behaviour of sodium chloride under compression was investigated by measurement of compaction forces and ejection forces. Saturated solution present at the crystal surfaces effected a reduction in friction at the inter-particulate boundary and between the particles and the die wall. Dry material formed compacts of higher strength than wet material except at low pressures. Subsequent drying of compacts prepared in the presence of moisture resulted in an increase in strength due to interparticulate recrystallisation.
The use of photoelastic techniques in the measurement of die-wall stress in tabletting
Authors: RIDGWAY K
Published: April 2011

A new technique is described for the observation of the stresses acting during a compaction operation. Pharmaceutical materials have been compressed in a Perspex die and viewed by polarised light. By using ancillary Perspex strain gauges both radial pressure and shear stress at the die wall may be determined from the interference pattern. Although Perspex is not a strong material, pressures up to about 12 tons/in2 could be contained, and a hard tablet extracted from the die. The entire pressing operation is recorded on ciné film for later analysis.
Water vapour transmission properties of applied polymer films
Authors: BANKER GILBERT S , GORE ASHOK Y , SWARBRICK JAMES
Published: April 2011

The rates of moisture uptake by film-coated tablet matrices containing calcium chloride have been determined as a function of polymer coat formulation, film coat thickness and calcium chloride content of the matrix. The more hydrophilic polymer film formulations were less effective in reducing the rate of moisture uptake by the tablet matrices. A linear relation was observed between rate of moisture uptake and film thickness, in contrast to the log-log relationship obtained in previous work using the same systems cast as free films. Decreasing the calcium chloride content of the matrix caused an overall lowering of the moisture uptake rate. The results indicate that the water vapour transmission characteristics of these polymer film systems are not the same when assessed using the rate of moisture uptake of tablets coated with these films as when using the rate of water vapour transmission through the free films. It is suggested that films should not be accepted or rejected solely on the basis of transmission rates across free films but that due consideration should be given to the more meaningful moisture uptake rates of the film-coated dosage form.
The metabolism of ethionamide and its sulphoxide
Authors: JOHNSTON J P , KANE P O , KIBBY M R
Published: April 2011

The fate of orally administered ethionamide (2-ethyl-4-thiocarbamoylpyridine) and ethionamide sulphoxide in man, rats, mice and dogs has been examined. Though spontaneous interconversion between the two antituberculosis drugs does not take place, there was extensive interconversion in vivo, both appearing in the blood within 15 min of dosing irrespective of which compound was administered. Species differences were evident in both the rate of metabolism and in the ethionamide: ethionamide sulphoxide ratio. Apart from this interconversion, ten probable urinary metabolites were detected. These consisted of six fluorescent and four non-fluorescent metabolites, three of the latter being identified as 2-ethylisonicotinamide, 2-ethylisonicotinic acid and inorganic sulphate. A scheme is proposed to cover part of the common metabolic route of the two drugs.
Ionization constants and water solubilities of some aminoalkylphenothiazine tranquillizers and related compounds
Authors: GREEN A L
Published: April 2011

A simple graphical method is described for deriving the ionization constants of poorly soluble organic bases from the pH dependence of the water solubility. Ionization constants and water solubilities of 13 aminoalkylphenothiazines and related drugs have been determined using this procedure. Potent tranquillizing activity in this group of compounds is shown to be associated with a low water solubility at blood pH.
Analgesically active basic anilides: stereospecificity and structure of the basic group
Authors: CASY A F , HASSAN M M A
Published: April 2011

The synthesis of (RS)-, (R)- and (S)-N-(2-dimethylaminopropyl)propionanilide and the benzylmethylamino- analogues of methadone and isomethadone is described. The hot-plate activities in mice of the (S)- enantiomorphs of both the dimethylamino- and benzylmethylaminopropionanilides are greater than those of the corresponding (RS)- and (R)- forms, while the methadone and isomethadone analogues are inactive in the same test. These results support the view that 3-amino-1,1-diphenylpropyl- and basic anilide - analgesics differ in their modes of binding to the analgesic receptor site.
An in vitro model for soluble drug absorption
Authors: PERRIN JOHN
Published: April 2011

A physico-chemical model is proposed to simulate the transfer of a drug through a lipoidal membrane. The drug is transferred from a buffer of a pH found in the gut, through an immiscible organic liquid acting as the membrane, to a buffer of the plasma pH (7.4). The transfer of salicylic acid and amidopyrine obeys the theoretical equations. The apparatus used has the advantage that there is little or no danger of emulsion formation because of the lack of disturbance at the interface and the ease of removing samples for analysis.
Pharmacological properties of tetrahydropapaveroline
Authors: SANTI R , FERRARI M , TÓTH C E , CONTESSA A R , FASSINA G , BRUNI A , LUCIANI S
Published: April 2011

Tetrahydropapaveroline (thp) exerts β-sympathomimetic effects similar to those of isoprenaline. On guinea-pig isolated atria, thp elicits positive inotropic and chronotropic activities which are not abolished by previous reserpinization of the animals; on isolated mammalian heart these effects are associated with an increase in coronary flow. In the dog, thp increases myocardial contractile force and rate, elicits a hypotensive effect and stimulates respiratory activity in normal and reserpinized animals; when injected intra-arterially the drug causes vasodilatation. All the effects are prevented by the β-adrenergic blocking agents propranolol, dichloroisoprenaline and pronethalol. Structure-activity relationships between tetrahydroisoquinoline derivatives and their open-ring phenylethylamine congeners, which are closely related to sympathomimetic drugs, are discussed.
Some pharmacological effects and chemical properties of N-propargylnoratropine
Authors: DECSI L , VÁRSZEGI M K , NÁDOR K
Published: April 2011

N-Propargylnoratropine has been prepared from noratropine, and its structure proved by hydrogenation followed by alkaline hydrolysis. Some pharmacological effects of this compound have been compared with atropine. The central and peripheral cholinolytic activity is some 50% lower than that of atropine. There is a fourfold increase in the analgesic-disorientating action of atropine.
Chemical and pharmacological observations on some Hebe species
Authors: GRADY JUNE , LEWIS J J , MARTIN-SMITH M , MUIR T C , SUBRAMANIAN G
Published: April 2011

Examination of oven-dried leaves and twigs of four species of Hebe indigenous to New Zealand—H. stricta, H. odora, H. bollonsii and H. corriganii—has revealed D-mannitol and condensed tannins to be major constituents. Identification of some of the minor constituents, namely alkanes, fatty acids and aliphatic alcohols was achieved by means of gas-liquid chromatography. Pharmacological studies with the condensed tannin fractions of H. stricta and H. odora have indicated that the reputation of H. stricta as a constipatory agent is attributable to tannins; this agrees with earlier assumptions.
The mechanism of inhibition by salicylate of the pentose phosphate pathway in the human red cell
Authors: SMITH M J H , STURMAN J A
Published: April 2011

Salicylate inhibits the pentose phosphate pathway of glucose metabolism in human red cell haemolysates. The site of inhibition is concerned with glucose 6-phosphate and 6-phosphogluconate dehydrogenases and the mechanism of inhibition involves competition with nadp.
The rheology of some oil-in-water emulsions stabilized by condensed complex films
Authors: TALMAN F A J , DAVIES P J , ROWAN E M
Published: April 2011

The rheology of emulsions containing oleyl, lauryl or cetostearyl alcohol as the oil-soluble component has been examined. As the concentration of fatty alcohol was increased, three main types of behaviour were found. These could not be explained by the particle size distribution, phase weight ratio or internal phase viscosity. It is suggested that migration of oil-soluble component and subsequent formation of viscous gels in the aqueous phase accounted for the observed behaviour. The effects of temperature, type of oil phase and chemical constitution of water-soluble components, have also been examined.
Influence of dextrose on the viability of Bacillus subtilis
Authors: RICHARDSON G
Published: April 2011

Dextrose causes an increase in viable count of Bacillus subtilis and the effect is greater for spores than vegetative cells. The proportion of spores in which germination is initiated is not influenced by dextrose. During germination the ability of dextrose to affect the viable count is completely lost but re-appears as the germinated spore changes into a dividing vegetative cell. When spores are incubated in broth before plating in nutrient agar there is an increase in viable count followed by a fall before the increase in count due to division is detected. When plated in dextrose agar this initial rise is not seen and there is a fall in count before onset of division. The magnitude of the increase in count caused by dextrose is dependent on the method of plating. For maximum recovery of viable organisms the combination of roll-rube method with dextrose agar is to be preferred to surface plating with or without dextrose in the counting medium.
The effects of posterior pituitary hormones on isometric tension and isotonic shortening of the pig myometrium
Authors: KNIFTON A
Published: April 2011

Isotonic recording showed that uteri in the luteal stage of the oestrus cycle were more sensitive to oxytocin and vasopressin than those in the follicular stage. The uterine horn was more sensitive than the cervix. A comparison of isotonic and isometric recording revealed that the former exaggerated the response to oxytocin. Under isometric conditions there was no difference in sensitivity to oxytocin between progesterone-dominated and oestrogen-dominated uteri, but both were more sensitive than immature uteri. Tension developed in response to oxytocin was greatest in oestrogen-dominated, less in progesterone-dominated and least in immature uteri.
Acetylcholine in extracts and perfusates of urinary bladder
Authors: CHESHER G B
Published: April 2011

Tissue extracts of the urinary bladder of the rat, cat and guinea-pig contain an acetylcholine-like substance which is considered to be stored predominantly in post-ganglionic nerve fibres. An acetylcholine-like substance was liberated into the fluid bathing the isolated bladder of the guinea-pig and its output was increased 200-fold after transmural stimulation. The acetylcholine-like substance, both from bladder extracts (rat, cat and guinea-pig) and perfusates (rat), was found at the same Rf value as acetylcholine chloride when separated by paper chromatography in three solvent systems. It is concluded that the substance was acetylcholine.
A modification of a method for the evaluation of topical anaesthesia in the earthworm
Authors: SUSKEVICH JAMES , CAMPBELL ARTHUR H , LORD GEOFFREY H
Published: April 2011

The method of Block, Potts & Finney (1964) for the evaluation of local anaesthetic activity using the response of the earthworm tail to hydrochloric acid has been found to give false negative results with control solutions. This was because the acid progressively damaged and thus desensitized the tail. This has been overcome by arranging the test so that no tail is immersed in the acid more than three times during an assay.
The influence of anaesthetic agents on the formation of methaemoglobin induced by aniline in cats
Authors: McLEAN S , ROBINSON J , STARMER G A , THOMAS J
Published: April 2011

Administration of anaesthetic agents modifies the methaemoglobin formation induced by aniline in cats. The maximum amount of methaemoglobin is reduced, so too is the rate at which the methaemoglobin disappears. Studies with phenylhydroxylamine indicate that these changes are due to anaesthetics modifying the metabolism of aniline to phenylhydroxylamine rather than modifying the action of phenylhydroxylamine on systems within the red blood cell. The microsomal metabolism inhibitor SKF 525A has no effect on methaemoglobin formation induced by aniline.
The effect of various environmental factors on cocaine and ephedrine toxicity
Authors: PETERSON DONALD I , HARDINGE MERVYN G
Published: April 2011

The effect of environmental factors on the toxicity of ephedrine and cocaine has been examined and the results compared with those obtained with amphetamine. Ambient temperatures were identified at which these drugs have an “aggregation effect”, and isolated mice treated with ephedrine or cocaine were then forcibly exercised and the effect of increased motor activity on body temperature and mortality compared with the results obtained by grouping the animals together. In general, the toxicity of either drug is increased by a rise in ambient temperature. Both drugs produce an aggregation effect and forced exercise increases the toxicity of each drug as much as does grouping. In all parameters tested the effects of ephedrine and cocaine resemble qualitatively those of amphetamine, but are less potent. In mice given certain central nervous system stimulants the aggregation effect may be due to hyperpyrexia associated with increased spontaneous motor activity resulting from a greater response to external stimuli.
Effects of reserpine on the sensitivity of rat isolated uteri preparations to oxytocic drugs
Authors: KHAN I , QURESHI Z
Published: April 2011

Stimulant activity of the isolated uteri of female virgin rats to acetylcholine, 5-hydroxytryptamine, and oxytocin was examined quantitatively (4-point assay method) in anoestrus, induced oestrus (diethylstilboestrol 10μg/100 g body weight injected subcutaneously), reserpinized and stilboestrol-treated reserpinized animals. Each group had 30 animals. Reserpine was administered intraperitoneally in two doses each of 1 mg/kg body weight on the first and third days of dioestrus. The sensitivity to acetylcholine, 5-hydroxytryptamine and oxytocin of the uteri in induced oestrus was increased by 20, 86 and 730 times respectively. In the group of animals receiving reserpine alone the experiment could not be made due to persistant spontaneous activity (even up to 2 hr) of the uterine tissue. In the stilboestrol-treated reserpinized group, the sensitivity to all the oxytocic drugs was as low as in anoestrous tissue. Thus, stilboestrol injection failed to increase the sensitivity of the rat uteri to oxytocic drugs or to produce changes in the vaginal smear pattern. The possibility of progesterone being present in the tissue due to persistance of corpora lutea after reserpine is put forward.
Micelles as simple models of drug receptors
Authors: BECKETT A H , KIRK G , VIRJI A S
Published: April 2011

Some interactions of optically active N-alkyl-NN-dimethylalanine hydrobromide (alkyl betaine) micelles, representing model flexible drug receptors, with simple “drug” molecules, represented by a number of optically active amino-acids, choline derivatives and a dipeptide have been examined. Comparisons of these “drug-receptor” interactions have been made using a refractive index technique and an explanation of the difference in the degree of adsorption of different “drug” molecules at identical micelle surfaces is advanced.
A method for measurement and statistical analysis of large numbers of experimental tracings
Authors: CHRISTIANSON A H , DINNEEN L C , JAMES G W L , PERKINS A C
Published: April 2011

An accurate and rapid method of digitizing large numbers of experimental tracings is possible using a Pencil Follower (D-Mac). Its use in conjunction with a computer has meant that data, hitherto virtually unmanageable, can be subjected to full statistical analysis. An example of its application is cited.
Adrenoceptive receptors in the duodenum, aorta and atria of the rabbit
Authors: HILL ARNOLD J , KOHLI J D
Published: April 2011

pA10 values for the α-receptor blocking drug phentolamine against adrenaline, noradrenaline and phenylephrine were determined in rabbit aorta and duodenum, and for the β-receptor blocking drug propranolol, against adrenaline, noradrenaline and isoprenaline in rabbit atria and duodenum. The values for phentolamine against different amines were found to be similar, varying by less than half a log unit, between or within the tissues, as were the values for propranolol. These data provide quantitative evidence that α-receptors in the aorta and duodenum are similar, as are the β-receptors in the atria and duodenum, even though both types of receptor serve divergent functions in different tissues.
The biliary metabolites of butylated hydroxytoluene in the rat
Authors: LADOMERY L G , RYAN A J , WRIGHT S E
Published: April 2011

The biliary metabolites from intravenous and intraperitoneal doses of small amounts of [14C]butylated hydroxytoluene have been separated and estimated. The metabolites recognized were the alcohol (II), aldehyde (III) and acid (IV) together with small amounts of the diphenyl ethane (VI). Three other metabolites appear to be present in relatively large amounts. The pattern of metabolites in bile and urine has been compared. It is suggested that the relatively low excretion of the acid (IV) in the urine compared to bile is due to a selective reabsorption of this compound after biliary excretion.
Solubility and viscosity relations in the system ascorbic acid—water—polysorbate 80
Authors: NIXON J R , CHAWLA B P S
Published: April 2011

The solubility of ascorbic acid in dispersions of polysorbate 80 has been examined. Over a large region of the solubility range liquid crystal exists, bounded by isotropic liquid phases. Excess solubilizate separates out as crystalline material. The rheological properties are complex. Within the isotropic phases the viscosity is Newtonian, but as soon as liquid crystal is produced pseudoplastic or thixotropic flow occurs. In the centre of the liquid crystal region, there were concentrations exhibiting a “yield” value followed by relaxation before the usual thixotropic loop.
Some pharmacodynamic effects of the babesicidal agents quinuronium and amicarbalide
Authors: EYRE P
Published: April 2011

The intravenous injection of a therapeutic dose of quinuronium methylsulphate (1 mg/kg) causes a fall in blood pressure in sheep, which is partly prevented by mepyramine and abolished by atropine. Larger doses of quinuronium cause more marked hypotension and inhibition of respiratory movement, which are not affected by atropine. Quinuronium strongly increases the amplitude of contraction of the isolated rabbit heart. This effect is not antagonized by atropine or mepyramine. Contractions of plain muscle in the guinea-pig and sheep, and hypersecretion of gastric acid in the rat and of saliva in the sheep were all produced by quinuronium. The responses to acetylcholine were potentiated by quinuronium, an effect which was abolished by atropine. Amicarbalide isethionate by comparison was weakly active. The drug causes no change in blood pressure, smooth muscle contraction or salivary secretion, but stimulates gastric secretion and partially inhibits the actions of acetylcholine in these preparations.
Evaluation of potential antirheumatic drugs in vitro using lymphocytes and epithelial cells. The selective action of indoxole, methyl glyoxal and chloroquine
Authors: WHITEHOUSE M W
Published: April 2011

Anti-inflammatory steroids and non-steroid drugs rapidly inhibit the incorporation of radioactivity from tritiated uridine and thymidine into the nucleic acid fraction of cultured epithelial cells and lymphocytes obtained from sheep, rats, rabbits and chickens. Acidic (uncoupling) drugs were also found to inhibit protein synthesis in these particular cells, and protein and nucleic acid synthesis in other cells which were steroid-insensitive, DNA synthesis in epithelial cells and lymphocytes was inhibited by methyl glyoxal (pyruvaldehyde). Chloroquine selectively inhibited thymidine incorporation by the epithelial cells. Indoxole was a potent inhibitor of the metabolism of circulating lymphocytes incubated in protein-free media. These findings may indicate why some of these drugs suppress adjuvant arthritis in rats.
The fate of [14C]thalidomide in the pregnant hamster
Authors: HAGUE D E , FABRO S , SMITH R L
Published: April 2011

The embryotoxicity and fate of [14C]thalidomide in the pregnant European golden hamster have been investigated. Daily administration of thalidomide (1 or 2 g/kg orally) to pregnant hamsters on days 4–12 inclusive of pregnancy was not embryotoxic. [14C]Thalidomide (150 mg/kg) administered on the 204th hr of pregnancy is well absorbed and about 84% of the 14C is excreted in the urine and 9% in the faeces in the 3 days after dosing. The urinary 14C consists of thalidomide (3% of dose), α-(o-carboxybenzamido)glutarimide (26%), 2- and 4-phthalimidoglutaramic acids (8%), 2-phthalimidoglutaric acid (0.2%) and 2- and 4-(o-carboxybenzamido)-glutaramic acids plus 2-(o-carboxybenzamido)glutaric acid (27%). 14C is present in the embryo and the relative concentrations of radioactivity in the embryo and plasma are about the same at 4, 12 and 24 hr after dosing. At 4 hr after dosing the embryo contains mainly thalidomide, but at 12 hr this has largely disappeared and the 14C consists of seven hydrolysis products. The lack of embryotoxicity of thalidomide in the hamster is thus not due to an inability of the teratogen to penetrate to the conceptus.
Influence of the route of administration on the toxicity of some cholinesterase inhibitors
Authors: NATOFF I L
Published: April 2011

The acute median lethal doses of a series of cholinesterase inhibitors have been estimated in mice for different routes of administration Differences in the LD50 values obtained for intraperitoneal and oral routes (“hepatic” routes) and subcutaneous and intravenous routes (“peripheral” routes) suggest that the availability of the compound for metabolism by the liver is a major factor in their toxicity.
The metabolism of 5,5‘-methylenedisalicylic acid in various species
Authors: Davison Clarke , Williams R T
Published: April 2011

Commercial methylenedisalicylic acid has been shown to be grossly impure. Pure 5,5′-methylendisalicylic acid (4,4′-dihydroxydiphenylmethane-3,3′-dicarboxylic acid) has been prepared and labelled with 14C. The fate of the pure compound in the rat, mouse, hamster, rhesus monkey, rabbit, guinea-pig and chicken has been investigated. The compound is excreted entirely unchanged in the urine and faeces in all the above species and no metabolites have been found. The biliary excretion of the injected compound is high (50–60%) in the rat and dog and low (5%) in the guinea-pig and rabbit. In the monkey, rabbit and guinea-pig, the compound is excreted almost exclusively in the urine. In the rat about 50% of the dose is excreted in the faeces. In the mouse and hamster, the main route of excretion is the urine, about 10% appearing in the faeces.
Estimation of the stability of dry horse serum cholinesterase by means of an accelerated storage test
Authors: Cole B R , Leadbeater L
Published: April 2011

The thermal inactivation of dry horse serum cholinesterase was found to obey first order kinetics over the temperature range 38–140°. Rogers' (1963) accelerated storage test was applied to this reaction and gave estimates of the rate coefficients and energy of activation of the inactivation reaction which agreed with the values determined in isothermal experiments. The stability of the enzyme preparation at 38° predicted by means of the accelerated storage data coincided with that found by isothermal storage of the enzyme at 38°.
The distribution of salicylate in mouse tissues after intraperitoneal injection
Authors: Sturman J A , Dawkins P D , McArthur N , Smith M J H
Published: April 2011

The concentrations of salicylate and its principal metabolites were measured in blood, liver, brain, kidney, heart, spleen, diaphragm and skeletal muscle after the intraperitoneal injection of a fixed amount of radioactive salicylate and varying doses of unlabelled salicylate. The patterns of distribution of salicylate in the various organs with time were similar, the peak level being attained in 30–60 min after injection. Salicylate was eliminated from the blood after 8 hr but persisted in liver in measurable amounts up to 24 hr.
The assignment of absolute configurations to the individual enantiomorphs of phenylpropylmethylamine and pipradrol hydrochloride
Authors: Hemingway R J
Published: April 2011

The configuration of the C-2 asymmetric centre of (—)-phenylpropylmethylamine (N-methyl-2-phenylpropylamine) has been related by a stereospecific route to that of the analogous centre of (+)-(S)-hydratropic acid. The configuration at the C-2 asymmetric centre of (—)-pipradrol (diphenylpiperid-2-ylmethanol) hydrochloride has been related by a stereospecific route to that of the analogous centre of (+)-(R)-pipecolic acid.
Kinetics of buccal absorption of amphetamines
Authors: Beckett A H , Boyes R N , Triggs E J
Published: April 2011

The buccal absorption of amphetamine, methylamphetamine and dimethylamphetamine in solutions at pH 8·16 and 9·18, was measured in man after 1, 2, 3, 4, 5 and 10 min. The recovery of the drugs from the buccal membrane after uptake was also measured by washing out the mouth for varying times with buffer solutions. An analogue computer model of the biological system was used and the kinetic parameters for the buccal absorption of the amphetamines were calculated.
Inhibition of amine uptake in the mouse heart by some new “thymoleptic” drugs
Authors: Waldeck B
Published: April 2011

A number of new and established thymoleptic drugs were given to mice. Their inhibitory action on the uptake of [3H]metaraminol and [3H]noradrenaline in the heart was investigated. Among the compounds tested a monomethylamino-derivative was in general 2–3 times more potent than the corresponding dimethyl-amino-derivative. The phthalan derivative 3,3-dimethyl-1-(3-methylaminopropyl)-1-phenylphthalan (Lu 3–010) was as efficient as protriptyline in all the tests performed. Changes in the substitution of the phthalan skeleton influenced the activity critically. As it is devoid of anticholinergic activity Lu 3–010 appears to be the most specific inhibitor of the amine transport mechanism of the adrenergic cell membrane found so far.
An investigation of the effects of angiotensin on the release of neurohumoral transmitters at motor, adrenergic and cholinergic nerve terminals
Authors: Hughes I E
Published: April 2011

On the sciatic nerve-gastrocnemius-soleus muscle preparation of the cat, angiotensin (1–5 μg/kg, i.v.) potentiated the twitch response to maximal and submaximal stimulation of the sciatic nerve and produced partial reversal of an incomplete tubocurarine blockade. These actions could not be explained in terms of increased acetylcholine release since they were not seen in isolated motor nerve-striated muscle preparations and were probably secondary to the cardiovascular actions of angiotensin. Blockade of conduction in the postganglionic cholinergic nerves in the guinea-pig isolated ileum preparation by cooling or anoxia antagonized the response of this tissue to angiotensin. These procedures left the response to exogenous acetylcholine unchanged though they removed the cholinergic component of the response to angiotensin which is known to be present in this tissue. No evidence of increase in catecholamine output could be found in preparations of guinea-pig and rabbit vasa deferentia or rabbit duodenum responding to submaximal stimulation of their adrenergic nerves. It is concluded that angiotensin has no direct action on the stores of neurohumoral transmitter at motor, postganglionic cholinergic or postganglionic adrenergic nerves and that its known acetylcholine releasing action in the isolated ileum results from stimulation of the ganglia.
A note on the subcellular distribution of adipose tissue noradrenaline
Authors: Gessa G L , Congiu S , Spano P F , Musinu C
Published: April 2011

The distribution of noradrenaline between the residue and high-speed supernatant of adipose tissue homogenates in rats, guinea-pigs and cats has been examined. Most of the noradrenaline is in the supernatant fraction; little is in the 100,000 g fraction.
Potentiation of acetylcholinesterase by a series of quaternary ammonium compounds
Authors: Roufogalis B D , Thomas J
Published: April 2011

Eleven spiran, and two non-spiran, quaternary ammonium compounds have been examined and some of these compounds found to potentiate the hydrolysis of acetylcholine by acetylcholinesterase at high substrate concentrations. The experiments were made in three reaction media, each differing in its ionic composition. The results obtained in these media differ both quantitatively and qualitatively. The mechanism of the potentiation is discussed in terms of the effect of quaternary ammonium compounds on the deacetylation step of acetylcholine hydrolysis.
Application of the analogue computer to pharmacokinetic and biopharmaceutical studies with amphetamine-type compounds
Authors: Beckett A H , Tucker G T
Published: April 2011

The kinetics of absorption, metabolism, and excretion of (+)-amphetamine and (+)-methylamphetamine, after oral administration of “free” dosage forms to man, under controlled acidic urine conditions, have been examined using an electronic analogue computer. This device has also been used to determine the in vivo rate of release of the drugs from hard gelatin capsule dosage forms and prolonged-release preparations. In vivo drug release from the prolonged-release preparations was correlated with in vitro drug release data.
The effect of temperature on end-plate depolarization of the rat diaphragm produced by suxamethonium and acetylcholine
Authors: Harris J B , Leach G D H
Published: April 2011

End-plate depolarization in the rat isolated diaphragm by suxamethonium and acetylcholine was measured at 37° and 20° using a modification of the method of Fatt (1950). At 20° the response of the motor end-plates to the depolarizing activity of acetylcholine and suxamethonium was enhanced. Since the presence of neostigmine in the bath fluid did not modify the response of the motor end-plates to the depolarizing activity of suxamethonium at 37°, the results suggest the enhanced response of the motor end-plates at 20° is due to a change in the properties of the motor end-plate, and not to a change in the activity of cholinesterases present in the tissues.
The effects of tremorine and oxotremorine in hyperthyroid mice
Authors: Waite R , Spencer P S J
Published: April 2011

Hyperthyroid mice exhibit only transient low-level tremor and hypothermia in response to tremorine and oxotremorine, yet the peripheral effects of these two agents are similar in intensity and duration to those elicited in control animals. These findings support the theory that tremor and hypothermia are both central effects and separate from the peripheral muscarinic actions of tremorine and oxotremorine. Of several possible explanations for the reduction in tremor and hypothermia, the most likely appears to be a potentiation of central adrenergic mechanisms in the hyperthyroid mice.
Role of pH in the coacervation of the systems: Gelatin - water - ethanol and gelatin - water - sodium sulphate
Authors: Khalil Saleh A H , Nixon J R , Carless J E
Published: April 2011

Phase boundary determination, coacervate volume measurements and analysis of the phases have been made to assess the influence of pH on the coacervation of gelatin solutions by ethanol and sodium sulphate. Coacervation was found to be pH dependent. In the ethanol system coacervation was noticeable only within a pH range in the vicinity of the isoionic point; at other pH values either a viscous gel phase or floccules occurred. In the sodium sulphate system, coacervation occurred at all pH values examined. The effect of pH in changing the overall charge on the gelatin molecule is explained in relation to the formation of gelatin coacervates. Finally, the role of the coacervate phase in the microencapsulation of oil and solid particulates is discussed.
Use of the analogue computer to examine the quantitative relation between urinary pH and kidney reabsorption of drugs partially ionized at physiological pH
Authors: Beckett A H , Boyes R N , Tucker G T
Published: April 2011

A method, involving the use of an analogue computer, is described for determining a quantitative relation between measured urinary pH and the kidney tubular reabsorption of certain drugs under normal conditions of fluctuating urinary pH. The method is based on the use of drug excretion versus time profiles under normal conditions and of absorption, metabolism and excretion rate constants, determined under conditions of controlled urinary pH, e.g. constant acidic pH (<5) in the case of basic drugs. In support of the theoretical treatment, experimental results, using amphetamine as a model drug, are presented. The implications of the method are discussed with respect to the evaluation of drug formulations under normal urinary pH conditions.