bluuebunny/crossref_metadata_2025 huggingface dataset:
Method for the Quantitative Estimation of Strychnine and Brucine in Nux Vomica by Paper Electrophoresis
Authors: Bardhan D K , Chakravarty Diptish
Published: April 2011

A method for the quantitative separation and estimation of strychnine and brucine in nux vomica seeds has been described. The method involves extraction of total alkaloids, electrophoretic separation in a buffer medium and subsequent estimation in spectrophotometer after elution in suitable solvent. The method is precise and accurate
Polymorphism of Cortisone Acetate
Authors: Callow R K , Kennard Olga
Published: April 2011

Evidence is presented that cortisone acetate occurs in at least five distinct crystalline forms. Four of these forms are unstable in presence of water and change to the stable Form I. Physical data, including spectroscopic and X-ray crystallographic constants, are recorded, and the application of these physical measurements to the recognition of the different forms, and the value of doing this with pharmaceutical preparations are discussed
The Molecular Properties of Ghatti Gum: A Naturally Occurring Polyelectrolyte
Authors: Elworthy P H , George T M
Published: April 2011

An authenticated sample of ghatti gum from Anogeissus latifolia has been fractionated by ethanolic precipitation (Fraction I), and chromatography on silica gel (Fractions 2 and 3). The equivalent weights found were 1,750, 1,800 and 2,040 respectively. The sodium salts of the fractions have been studied in various salt solutions by viscosity and light scattering methods. From the latter the molecular weights (= 2·1, 2·7, and 2·6 ± 106 respectively), radii of gyration, and some idea of molecular shape have been obtained. The molecule appears to be rod shaped. The expansion factors of the molecules calculated from the light scattering and the viscosity data agree with each other. Reasons for the difference in the values of the calculated and observed second virial coefficients are discussed.
Identification of the thiazide diuretic drugs
Authors: PILSBURY VALERIE B , JACKSON J V
Published: April 2011

A method for detecting and identifying ten thiazide diuretic drugs in tablets, gastric washings and urine by ultraviolet spectrophotometry and paper chromatography is described. The thiazides can be detected by absorption maxima in the region 264 to 294mμ at concentrations of 5 μg/ml or lower. Identification is by ascending high temperature reverse phase paper chromatography using tributyrin treated paper and developing for 20 min at 90° with a phosphate buffer (pH 7614). Further differentiation is obtained with the solvent system amyl alcohol—0 880 ammonia (9:1) on Whatman No. 1 paper. The thiazides are located as absorbing or fluorescent spots in ultraviolet light (2534 Å) and these are confirmed by the stable red colour given by an alkaline sodium 1,2-naphthaquinone-4-sulphonate spray reagent. Many of these diuretics are co-extracted with barbiturates and may interfere with barbiturate determinations.
Metal binding tendencies of various antibiotics
Authors: NIEBERGALL P J , HUSSAR D A , CRESSMAN W A , SUGITA E T , DOLUISIO J T
Published: April 2011

A method to determine the presence of metal-drug complexes in dilute solutions is described. Using this method cycloserine was found to complex with cupric, nickelous, zinc and cobalt ions; streptomycin and novobiocin complexed with cupric ions; erythromycin complexed with cobalt ions, and chloramphenicol exhibited no metal binding tendencies. Various penicillins were found to interact with zinc and cupric ions. Preliminary investigations suggest that cupric ions, rather than simply complexing with penicillin as suggested by previous workers, promote the degradation of penicillin to penicilloic acid. Evidence is presented to confirm the presence of penicilloic acid in reaction mixtures initially containing penicillin G or V and cupric ions, and to establish that the reaction follows second order kinetics and ceases when all available cupric ion has been consumed. Good correlation was noted for these results and previous work which showed the effects of metal ions on the antibacterial properties of penicillin.
Apparatus for accelerated temperature cycling
Authors: CARLESS J E , FOSTER A A , JOLLIFFE G O
Published: April 2011

An automatic control unit, activating electrically operated solenoid valves, is used to regulate the flow of “hot” and “cold” water from two thermostated baths to the jacket of a reaction vessel so that the temperature of a liquid sample within the vessel follows a highly reproducible programmed cycle. A comparison is made of the temperature hysteresis between 23–33° during a 16 min cycle, when the flow rates to the vessel are changed and when the valves are operated manually. The adjustment of temperature hysteresis to effect the accelerated storage testing of liquid preparations is described.
The diuretic activity of clorexolone and some related phthalimides and 1-oxoisoindolines
Authors: CORNISH E J , LEE G E , WRAGG W R
Published: April 2011

N-Substituted 4-chloro-5-sulphamoylphthalimides showed diuretic activity in the rat. Reduction of the carbonyl group in the position para to the 5-sulphamoyl group in the phthalimides produced even more active compounds. The relationship between potency and the nature of the N-substituent was examined in 32 phthalimides and 10 reduced derivatives. Maximum potency was found in the N-cycloalkyl and N-cycloalkylmethyl compounds, one of which, 5-chloro-2-cyclohexyl-1-oxo-6-sulphamoylisoindoline (clorexolone), was 300 times as active as chlorothiazide in the rat. This compound was examined in more detail in both the rat and the dog.
The analgesic and related properties of 6-deoxy-6, 6-ethylenedioxy-7, 8-dihydro-14-hydroxycodeine hydrochloride
Authors: BARRON D I , HALL PATRICIA L , VALLANCE D K
Published: April 2011

The compound 6-deoxy-6, 6-ethylenedioxy-7, 8-dihydro-14-hydroxycodeine hydrochloride possesses analgesic potency greater than either morphine or codeine when examined by a variety of methods in mice and rats. Compared with these two analgesics the compound showed greater separation between effective analgesic doses and doses producing inhibition of gastrointestinal motility or death, but not for mydriasis or respiratory depression. Some evidence for a lower addictive liability than morphine is discussed.
The electrically stimulated ileum of the guinea-pig for measuring acetylcholine antagonism at different sites
Authors: LEACH G D H
Published: April 2011

The transmurally stimulated guinea-pig ileum preparation was used to determine quantitatively the antagonism developed by hexamethonium and atropine against the emptying reaction and the longitudinal muscle response. Hexamethonium in concentrations of 1·5–6·0 μg/ml blocked the emptying reaction but larger doses, 8–10 μg/ml, failed to depress the longitudinal response to less than 50% of its original height. Atropine, on the other hand, in concentrations of 0·001–0·02 μg/ml, reduced the longitudinal response without affecting the emptying reaction. Thus, the preparation discriminates between acetylcholine antagonists acting at either the nicotinic or muscarinic site.
Enlargement of salivary glands in rats after chronic administration of physalaemin or isoprenaline
Authors: BERTACCINI G , DE CARO G , CHELI R
Published: April 2011

Chronic administration of physalaemin and isoprenaline to rats produced a significant salivary glands enlargement which was moderate (34% fresh weight increase and 48% dry weight increase compared with control glands) after the peptide administration and striking after the amine (630% fresh weight increase and 600% dry weight increase compared with control glands). Physalaemin caused only hypertrophy of the gland, whereas isoprenaline induced a marked hyperplasia.
Pyrazolotriazines: a new class of tumour-inhibitory agents
Authors: BALDWIN R W , PARTRIDGE M W , STEVENS M F G
Published: April 2011

A series of pyrazolo-as-triazines have been screened for tumour-inhibitory activity against sarcoma S 180 in mice and a methylcholanthrene-induced tumour in rats. The antitumour activities of ethyl 4-aminopyrazolo[3,2-c]-as-triazine-3-carboxylate (Ig), 6-acetyl- and 6-iodoacetyl-3-methyl-4-methylenepyrazolo[3,2-c]-as-triazine (IIa and IIb respectively) against sarcoma S 180 exceed the inhibitory activity of 6-mercaptopurine against the same tumour.
Germination rate of spores of Bacillus megaterium
Authors: HAMBLETON R , RIGBY G J
Published: April 2011

THE most commonly accepted criteria of bacterial spore germination are loss of heat resistance, acquisition of stainability by simple stains and a change in absorbance (Wynne & Foster, 1948; Powell, 1951; Pulvertaft & Haynes, 1951; Levinson & Sevag, 1953). To these might be added a decrease in resistance to certain germicides. Although it has been suggested that some of these changes occur simultaneously (Campbell, 1957), most of the evidence for this is qualitative rather than quantitative.
The effects of the addition of manganese dioxide to media on the viability of bacteria damaged by x-rays, phenol and radiomimetic agents
Authors: HARRIS N D , WHITEFIELD M
Published: April 2011

Suspensions of two strains of Escherichia coli were counted before and after damage by phenol, X-rays and radiomimetic substances on nutrient agar which had been treated in various ways with manganese dioxide. The medium after some treatments gave increased counts with cells damaged by phenol and dimethyl busulphan and with undamaged cells, the strains responding rather differently. The beneficial action of manganese dioxide was not due to the breakdown of peroxides in the medium and may be due to the adsorption of toxic substances from the medium.
The effect of peptone on the inactivation of a bacteriophage by chemical antimicrobial agents
Authors: BROWN W R L , THOMAS A H
Published: April 2011

BECAUSE of their intracellular parasitic nature, infectious virus particles are almost invariably closely associated with substances derived from the host organism. In the chemical disinfection of virus contaminated material, the possible interference in the action of the inactivating agent by extraneous organic matter is therefore of particular importance. Little quantitative information on such effects is available however. Peptone reduces the activity of formaldehyde, phenol and sodium hypochlorite against Bacillus subtilis spores (Bullock & Rawlins, 1950, 1954) and it has been used here to illustrate the effect of non-viral organic matter on the chemical inactivation of a bacterial virus.
A method for the evaluation of some oral prolonged-release forms of dexamphetamine in man, using urinary excretion data
Authors: BECKETT A H , TUCKER G T
Published: April 2011

ALTHOUGH urinary excretion studies (Campbell, Nelson & Chapman, 1959; Chapman, Shenoy & Campbell, 1959; Shenoy, Chapman & Campbell, 1959) have been used as a technique to evaluate prolonged-release dosage forms of amphetamine, the significance of the results is in doubt because of the use of non-specific assay methods and the failure to control urinary pH. The use of radioactive material has indicated the similarity between a dose of 5 mg amphetamine three times a day and a 15 mg prolonged release preparation (Rosen, Tannenbaum, Ellison, Free & Crosley, 1965).
The metabolism and excretion of lignocaine in man
Authors: BECKETT A H , BOYES R N , APPLETON P J
Published: April 2011

The urinary excretion of lignocaine and monoethylglycinexylidide (megx) has been studied in man. The finding that megx is a major metabolite of lignocaine in man is discussed in relation to studies in animals reported by other workers. An analogue computer model was constructed to simulate the metabolism and excretion of lignocaine. By varying the model parameters it was possible to obtain good agreement between the calculated and empirical excretion data for both lignocaine and its metabolite megx. Because of this good agreement, the computer was used to predict body levels of the compounds after a dose of lignocaine.
Comparative anatomy of the leaves of Voacanga schweinfurthii Stapf and Voacanga africana Stapf
Authors: NEWCOMBE F , PATEL B A
Published: April 2011

There is a marked similarity in the anatomical structures of the leaves of the closely related species Voacanga schweinfurthii and V. africana which are here described and compared. The evidence suggests that these two species should be considered as a single species.
Histamine gastric ulceration and its prevention by degraded carrageenan: the effect of aminoguanidine sulphate
Authors: ANDERSON W , SOMAN P D
Published: April 2011

Pretreatment of the guinea-pig with intravenous aminoguanidine sulphate, a drug believed to inhibit histaminase, changes the gastric ulcer response following a dose of histamine acid phosphate (2·5 mg/kg) which elicits a submaximal ulcer response, to that of a dose (5 mg/kg) which normally elicits a maximal gastric ulcer response. A reduction in the volume and acidity of secretion also occurs. Intraduodenal administration of degraded carrageenan prevents this action of aminoguanidine. Conversely, in the presence of aminoguanidine, carrageenan fails to protect against histamine ulceration.
Radial voidage variation in randomly-packed beds of spheres of different sizes
Authors: RIDGWAY K , TARBUCK K J
Published: April 2011

The packing arrangement of the particles in a tablet die, before pressing, has no hitherto been considered as a variable in the tabletting process. Because of the complexity of this subject, the present investigation has been restricted to monosized and binary mixtures of spheres in a cylindrical container. The container could be revolved at speeds in excess of 1,000 rpm so that the thickness of an annular layer of water could be measured. From this, the voidage at any radial position could be found. The plot of voidage against distance from the cylindrical wall is a wave form which is damped out after about 5 particle diameters. For packings of monosized spheres the oscillations are regular. There appear to be two kinds of binary mixtures, those in which the particle sizes are similar, and those where the diameter ratio is greater than 0·4. The voidages calculated by suitably weighting the values for each component are in agreement with the measured voidages of the first kind but not with those of the second. Because there is an initial distribution of voidage, it is concluded that there must be some radial movement of the particles during the compacting operation.
Some angular properties of magnesia and their relevance to material handling
Authors: JONES T M , PILPEL N
Published: April 2011

By measuring the angular characteristics of magnesia over a range of particle sizes from 30–3000 μ, it has been possible to determine the factors which influence the shapes of heaps, cones and wedges of the material, formed under a variety of experimental conditions. The relevance of the measurements to quality control, flow-ability, hopper and chute design and material handling is discussed.
Cortisone acetate crystal forms
Authors: CARLESS J E , MOUSTAFA M A , RAPSON H D C
Published: April 2011

Infrared spectroscopy and differential scanning calorimetry data are given for the characterisation of three anhydrous and two hydrated crystal modifications of cortisone acetate. All forms revert to the same form on heating to 200°. The amount of hydration estimated from thermal analysis varies from half to one molecule of water per molecule of cortisone acetate. Methods for the preparation of the five forms are described emphasising the importance of solvent composition, particularly its water content. Interconversion of these forms under various conditions such as grinding, contact with water and heat treatment is discussed.
Enzymatic decyanation of cyanocobalamin in rat tissues
Authors: CIMA L , LEVORATO C , MANTOVAN R
Published: April 2011

Cyanocobalamin is decyanated in vitro to hydroxocobalamin by rat liver and kidney. This appears to be due to an enzyme system which we have called “cyanocobalamindecyanase”. The enzyme is in the soluble fraction of the cells; it requires reduced cozymases and flavins and has an optimum pH of 7.2 under anaerobic conditions. This is consistent with the fact that conversion of cyanocobalamin to hydroxocobalamin and/or its reduced forms (B12r, B12s) involves a reductive process in the earliest stage of the biosynthesis of coenzyme B12.
Synthesis and antiprotozoal activity of some nitro(nitroaryl)imidazoles
Authors: ELLIS G P , EPSTEIN C , FITZMAURICE C , GOLBERG L , LORD G H
Published: April 2011

A series of 5(4)-nitro-4(5)-nitroarylimidazoles has been synthesized and their in vitro antifungal and antiprotozoal activities have been studied. The compounds may be prepared by dinitration of an arylimidazole or by mononitration of either an aryl-nitroimidazole or a (nitroaryl)imidazole. In some of the compounds the ring nitrogen atom has been substituted. Several compounds exhibit high in vitro antitrichomonal activity against Trichomonas vaginalis and T. foetus, and a moderate activity against Histomonas meleagridis and Entamoeba histolytica. The chemical structure and antimicrobial activity of these and other imidazoles previously studied are briefly discussed.
Probable conformations of the analgesically active basic anilide N-[(2-benzylmethylamino)propyl]-propionanilide
Authors: CASY A F , HASSAN M M A
Published: April 2011

A spectroscopic (ultraviolet, infrared and nuclear magnetic resonance) study of N-[(2-benzylmethylaminp)propyl]propionanilide hydrochloride is reported and probable conformations of this molecule (in which the phenyl group and amide function are non-planar, the protonated basic centre lies close to the amido-nitrogen atom, and the secondary methyl group is removed from the region above the aromatic plane) proposed on the basis of the spectroscopic results. Differences in analgesic stereospecificity and basic group structure between enantiomorphs of methadone and N-[(2-benzylmethylamino)propyl]propionanilide are discussed in terms of the probable conformations of the two analgesics.
Molecular interactions of caffeine with o-, m- and p-iodobenzoic acids and o-, m- and p-fluorobenzoic acids
Authors: DONBROW M , BEN-SHALOM H
Published: April 2011

The solubilities of o-, m- and p-iodo- and fluorobenzoic acids in aqueous solutions of caffeine increase linearly with caffeine concentration due to complex-formation. Insoluble complexes are formed by the o- and m-acids and soluble ones by the p-acids. Approximate 1:1 stability constants have been evaluated from the phase diagrams and their values are considered in relation to possible mechanisms of complex-formation.
Viscosity of phospholipid sols
Authors: PERRIN J , SAUNDERS L
Published: April 2011

The viscosities of lysolecithin sols in water were found to be Newtonian at the concentrations investigated. A Couette viscometer was used. In the mixed sols containing both lysolecithin and lecithin, thixotropy was absent at all ratios and only the sol with a high lecithin fraction showed some non-Newtonian behaviour. The axial ratio of the mixed micelles calculated by the Simha method varies with the lecithin/lysolecithin ratio, rising to a maximum when the phospholipid mixture is of one mole lecithin to two moles lysolecithin. This phenomenon is probably due to the packing of the various hydrophobic groups in the micelle.
Uncoupling of oxidative phosphorylation by glycyrrhetic acid, fusidic acid and some related triterpenoid acids
Authors: WHITEHOUSE MW , DEAN P D G , HALSALL T G
Published: April 2011

Some new derivatives of 18α- and 18β-glycyrrhetic acid and oleanolic acid were tested for their ability to inhibit phosphorylation coupled to succinate oxidation in rat liver mitochondria. Glycyrrhetic acid is a potent uncoupler of oxidative phosphorylation (approaching 2,4-dinitrophenol in potency); uncoupling activity is dependent upon each of the following functional groups: 3-hydroxy, 11-oxo and 30-carboxyl groups. Inversion of the configuration at C-18 (D/E ring junction) or replacement of the 11-oxo-12-ene system in ring C by the 9(11),12-diene system in glycyrrhetic acid abolished uncoupling activity. By contrast, the hemisuccinates (3-O-carboxypropionyl derivatives) of 18α-glycyrrhetic acid and of the 18β-9,12-diene acid were moderately potent uncoupling agents but less active than 18β-glycyrrhetic acid. The uncoupling activity of these hemisuccinates could not be attributed to the carboxypropionyl group alone. Structural analogues of various glycyrrhetic acid derivatives prepared from oleanolic acid (with the carboxyl group at C-28) were less active in uncoupling oxidative phosphorylation than the corresponding compounds in the glycyrrhetic acid series (with the carboxyl group at C-30). The uncoupling activity of some derivatives of two naturally occurring tetracyclic triterpenoid acids, polyporenic acid A and fusidic acid, was also investigated and found to largely depend upon their chemical structure. The possible application of these compounds as drugs in man is discussed.
Interaction of anti-inflammatory drugs with serum proteins, especially with some biologically active proteins
Authors: Mizushima Y , Kobayashi M
Published: April 2011

The interaction of clinically established anti-inflammatory drugs with some proteins has shown these drugs to strongly inhibit heat coagulation of whole serum at a concentration attainable in the sera of patients. Phenylbutazone and sodium salicylate do not inhibit the biological activity of three biologically active and labile serum proteins, namely, necrotizing factor, heterogenous serum and complement. However, they do influence the effect of heat on these proteins. The relation between this drug action in vitro and the possible mode of action of the proteins in vivo is discussed.
The effect of a non-ionic surfactant upon the antifungal activity of benzoic acid
Authors: Humphreys K J , Richardson G , Rhodes C T
Published: April 2011

The effect of a non-ionic polyoxyethylene surfactant upon the fungicidal activity of benzoic acid has been investigated by a viable count method. The results show that theories equating antimicrobial activity to the concentration of non-micellar preservative are inadequate. The significance of these findings is discussed and some possible additional factors involved in the fungicidal process indicated.
Some observations on the use of absorbance measurements in bacteriology
Authors: Rye R M , Wiseman David
Published: April 2011

ABSORBANCE measurements are commonly used in bacteriology to follow the growth of cultures and for standardizing cell suspensions. This communication reports some investigations into the relation between absorbance and dry weight of washed cell suspensions and growing cultures of Escherichia coli.
The preparation and properties of (+)- and (−)-guanoxan
Authors: Stenlake J B , Breimer D D , Smail G A , Stafford Anne , Bowman W C
Published: April 2011

(±)-2-Aminomethyl-1, 4-benzodioxan has been resolved into its optically active isomers: (+)- and (-)-guanoxan have been synthesized from these. The pharmacological effects of racemic-guanoxan and of the two optical isomers have been compared on the isolated central ear artery of the rabbit, on the pithed rat in which pressor responses were evoked by stimulation of the thoraco-lumbar sympathetic outflow, and on the pre- and post-ganglionically stimulated nictitating membrane of the cat. The two isomers were equipotent in producing adrenergic neuron blockade. Initial catecholamine release was weak in the cat, but occurred more powerfully in the rabbit ear artery and in the rat. Ability to produce this effect resided mainly with the (+)-isomer. α-Adrenoreceptor blocking activity was detectable in the rat and was produced mainly by the (+)-isomer suggesting that its stereochemical configuration corresponds to that of D-(-)-noradrenaline. Ganglion blockade was an unimportant action of the compounds, but both isomers possessed weak atropine-like activity in the rat.
The effect of alloxan diabetes upon adjuvant-induced arthritis in the rat
Authors: Best R , Spencer P S J
Published: April 2011

THE relation between inflammation and carbohydrate metabolism has been the subject of several investigations using acute inflammatory models such as the anaphylactoid reaction in the rat (Adamkiewicz & Adamkiewicz, 1959; 1960) and true anaphylaxis in the rat and mouse (Kraus, 1964; Gulbenkian, Yanell Grasso & Tabachnick, 1967; Dhar, Sanyal & West, 1967). These acute inflammatory reactions are depressed by the hyperglycaemia produced by alloxan (Adamkiewicz & Adamkiewicz, 1959; 1960), by 2-deoxyglucose (Goth, 1959), by glucose loading (Dhar & others, 1967) and by glucagon (Lefebvre & Van Cauwenberge, 1962).

Using the model of “adjuvant arthritis” in the rat, produced by the injection of Freund's adjuvant (Pearson, 1956), Kellett (1965) showed that this chronic arthritic condition was also suppressed when alloxan diabetes was induced in rats before an injection of adjuvant. The syndrome of adjuvant arthritis occurs in two phases, firstly an acute inflammatory oedema at the injection site which is followed after a latent period of about ten days by a secondary, chronic polyarthritis involving all limbs and the tail.

Because of the biphasic course of the inflammation, and the possible dependence of the chronic phase on the prior appearance of an adequate initial phase, we decided to investigate the effect of alloxan diabetes induced at various times during the development of the adjuvant arthritic syndrome.
Synthesis and pharmacological action of some N-alkyl morpholines and their salts
Authors: Beckett A H , Hunter W H , Kourounakis P
Published: April 2011

The preparation is described of some 2-hydroxy-2- and 4-alkylmorpholines by ring closure of the corresponding phenacyl hydroxyalkylamines. The influence of structure upon the ring closure reaction is examined and the weak pharmacological action of the title compounds on leptazol convulsions, the autonomic nervous system and in the mouse hot-plate test is discussed in relation to the reversed esters of pethidine.
The effect of acetylsalicylic acid, phenylbutazone and indomethacin on the binding of 11-hydroxysteroids to plasma proteins in patients with rheumatoid arthritis
Authors: Stenlake J B , Davidson A G , Jasani M K , Williams W D
Published: April 2011

Plasma concentrations of total and unbound 11-hydroxysteroids in patients with rheumatoid arthritis have been determined using a fluorimetric method before and after administration of acetylsalicylic acid, phenylbutazone and indomethacin. Unbound 11-hydroxysteroids were measured in plasma ultrafiltrates obtained using the Toribara apparatus. Enhancement and quenching of fluorescence by acetylsalicylic acid, phenylbutazone, and indomethacin, and heparin used as an anticoagulant in the blood samples, have been shown to be absent. The results show that acetylsalicylic acid, phenylbutazone and indomethacin given in recommended therapeutic doses for periods of one week have no significant effect on plasma protein-binding of 11-hydroxysteroids.
The effect of anti-inflammatory drugs on the protein-binding of 11-hydroxysteroids in human plasma in vitro
Authors: Stenlake J B , Williams W D , Davidson A G , Downie W , Whaley K
Published: April 2011

The effect of acetylsalicylic acid, ibufenac, indomethacin, oxyphenbutazone and phenylbutazone on the protein-binding of 11-hydroxysteroids in vitro at concentrations in excess of normal has been examined in human blood bank plasma, in plasma from women in the third trimester of pregnancy, and in plasma from patients after injections of tetracosactide. Phenylbutazone, ibufenac and indomethacin do not significantly affect the protein-binding of 11-hydroxysteroids. Oxyphenbutazone causes a decrease in the proportion of unbound 11-hydroxysteroids and acetylsalicylic acid produces an increase of unbound 11-hydroxysteroids.
The absolute configurations of the alkaloids of Physostigma venenosum seeds
Authors: Longmore R B , Robinson B
Published: April 2011

The absolute configuration of physostigmine has been established by correlating the configuration of its C-3a atom with that of the asymmetric carbon atom in (+)-3-ethyl-3-methoxycarbonyl-3-methylpropionic acid. Comparison of the optical rotatory dispersion spectra of physostigmine, Na-norphysostigmine, geneserine, physovenine and eseramine have shown that all five alkaloids have the same absolute configurations.
The influence of substitution in phenylacetic acids on their performance in the buccal absorption test
Authors: Beckett A H , Moffat A C
Published: April 2011

In the buccal test there is a linear relation between percentage absorption and alkyl chain length for a series of p-n-alkyl phenylacetic acids. Branching and cyclizing the alkyl chain reduces the percentage absorption. With the p-halogeno-acids, absorption increases as the atomic weight of the halogen atom increases; a chlorine atom is approximately equivalent to a methyl group in its effect on absorption. An oxygen atom between an alkyl group and ring is equivalent to reducing the chain length by one methylene group. The absorptions of α-methyl-substituted acids are greater than those of the unsubstituted acids.
Effect of organic matter and increased inoculum size on the minimum inhibitory concentration of crystal violet towards Staphylococcus aureus at various pH values
Authors: Adams E
Published: April 2011

The minimum inhibitory concentration towards Staphylococcus aureus of crystal violet at pH values 6, 7 and 8, increased when the inoculum size was increased or if egg albumen was added to the medium. When allowance was made for dye uptake, the minimum inhibitory concentration still exceeded that in the absence of organic matter. The increased minimum inhibitory concentration in the presence of muscle could in most cases be attributed to the removal of dye from solution.
Thermodynamics of micellization of some non-ionic surfactants in mixed solvents
Authors: McDonald C
Published: April 2011

The thermodynamics of micellization of three non-ionic surfactants in mixed solvents are reported. The contribution of the alkyl chains of the surfactant molecules to micellization is estimated from solubility data.
The absorption, metabolism and elimination of (±)-N-(2-benzoyloxyethyl)norfenfluramine (JP992) in man
Authors: BECKETT A H , SHENOY E V B , BROOKES L G
Published: April 2011

The urinary excretion of N-(2-benzoyloxyethyl)norfenfluramine (JP 992) was examined in man with normal and acidic urine after oral administration of the drug; 86–100% of the dose was excreted in 48 h as metabolites of the drug having m-trifluoromethylbenzyl and benzoyl moieties, but no unchanged drug was detected. Norfenfluramine, N-2-hydroxyethylnorfenfluramine, and a metabolite, which on treatment with zinc and hydrochloric acid gave norfenfluramine, were excreted in urine. N-2-Hydroxyethylnorfenfluramine and a second unidentified metabolite were also excreted as both sulphate and glucuronide conjugates.
Homogeneity of pharmaceutical dispersed systems
Authors: Hersey J A , Cook P C
Published: April 2011

Pharmaceutical dispersions include an extremely important group of formulations for the administration of drugs. A consideration of the homogeneity or dose uniformity requirements of some pharmaceutical dispersions, including tablets, capsules, ointments, suspensions, lotions, emulsions and suppositories is given. Assessment of homogeneity, assuming possible required limits of dose conformity, enables a calculation of the particle size requirements. These may be limited by parameters other than homogeneity, for example, sedimentation in suspensions and physical stability of emulsions. The concept of homogeneity applied to these systems is useful for following the progress of powder mixing or other dispersion operations. It is also useful in examining the feasibility of achieving the desired degree of dispersion. Dose conformity could be an extremely important problem in some cases, where standards do not exist.
Butobarbitone metabolism in man: identification of 3î-ketobutobarbitone
Authors: Grove J , Toseland P A , Draffan G H , Clare R A , Williams Faith M
Published: April 2011

After single 200 mg oral doses of butobarbitone (I) in man, 5·4% was excreted in urine unchanged and 28·2% as the 3î-hydroxy metabolite (II) in six days. A new metabolite, the ketone (III), was detected in urine following oral administration both of I and of II. Oxidation of the hydroxy to the ketone metabolite was demonstrated in vitro with the 9000g fraction of rat liver. Use was made of selective ion monitoring g.c.-m.s. methods in metabolite detection.
A comparison of the effects of chronic administration of ethanol and acetaldehyde to mice: evidence for a role of acetaldehyde in ethanol dependence
Authors: Ortiz Aurelio , Griffiths Peter J , Littleton John M
Published: April 2011

After chronic exposure to ethanol or acetaldehyde vapour in concentrations which depress locomotor activity, mice show similar behavioural changes during withdrawal, and there is some degree of cross dependence. Mice exposed to acetaldehyde vapour had blood acetaldehyde concentrations similar to those of ethanol-treated mice, but brain acetaldehyde concentrations were apparently lower. There was no accumulation of acetaldehyde in blood or brain in either group during chronic administration. Chronic ethanol or acetaldehyde administration to mice is associated with an increase in the concentrations of the brain monoamines noradrenaline, dopamine and 5-HT. Withdrawal of ethanol or acetaldehyde is associated with a further, rapid, transient rise in the brain catecholamines, noradrenaline and dopamine. These results suggest that acetaldehyde may play a role in some of the biochemical and behavioural changes associated with ethanol dependence.
The granulation of binary mixtures: the effects of the composition of the granulating solution and the initial particle size of one component on granule properties
Authors: Opakunle W O , Spring M S
Published: April 2011

The effect of total solvent volume and the presence of dissolved material (other than binder) in the granulating solution, on the properties of granules prepared from lactose: boric acid mixtures has been studied. The total volume of binder solution available to powder mixtures during massing determines the ultimate average size of granules produced. Part-dissolution of powders being granulated contributes significantly to the average granule size by increasing the total solution volume and reducing the amount of powder to be wetted. Although the amount of PVP (binder) dissolved in the granulating solution contributed very little to granule size at the concentration examined, the combined effect of total volume of solution and amount of PVP present in the granulating solution determines granule strength and porosity. The effect of the initial particle size of lactose in a binary mixture with boric acid differs from its effect reported for single component systems.
A thin-layer chromatographic procedure for the assay of labelled noradrenaline and its metabolites in tissues and in incubation medium
Authors: Vohra M M , Jayasundar S
Published: April 2011

A method for the extraction, separation and quantitative determination of [3H]noradrenaline [3H-NA] and its five major metabolites has been devised using thin layer chromatography. This procedure was used to study the pattern of 3H-NA and its metabolites in the total radioactivity of the tissues and that released spontaneously from the rat isolated vas deferens. Whereas in tissues 3H-NA represented almost all of the total radioactivity (94·8 ± 0·47%), in the samples of spontaneous outflow it represented only 16·8 ± 2·1%. The rest was mostly accounted for by the five metabolites, primarily 3H-DOPEG and 3H-MOPEG. These findings show that in the rat vas deferens 3H-NA is preferentially metabolized via the two glycol derivatives, i.e. 3H-DOPEG and 3H-MOPEG.
The role of copper in preventing gastrointestinal damage by acidic anti-inflammatory drugs
Authors: Boyle E , Freeman P C , Goudie A C , Mangan F R , Thomson M
Published: April 2011

The ability of several non-steroidal acidic anti-inflammatory drugs to cause ulceration when given as copper complexes has been examined. The damage caused by clopirac, niflumic acid and aspirin was virtually abolished when they were given as copper complexes whereas the damage caused by indomethacin, ketoprofen and (+)-naproxen was unaltered. The lack of ulceration with three of these preparations appeared to be correlated with a much reduced ability to inhibit prostaglandin synthesis as determined using an in vitro enzyme system.
Anabolic and androgenic activities, in rat, of some nandrolone and androstanolone esters
Authors: Chaudry M A Q , James K C , Ng C T , Nicholls P J
Published: April 2011

The anabolic and androgenic activities of the formate to undecanoate esters of nandrolone and formate to valerate esters of androstanolone, after intramuscular injection, have been determined in rat. The response to a given dose was measured as cumulative weight (the area under the plot of weight of indicator organ against time). Levator anus muscle was used to assess anabolic activity, and the sum of the cumulative weights for prostate and seminal vesicles for androgenic activity. Log dose-log cumulative weight plots were parallel, and biological activities were expressed as the cumulative weight corresponding to a 2 μM dose, calculated from the regression lines. Anabolic-androgenic ratios for both series were calculated and were found to be minimum in the region of the propionate and butyrate. The anabolic-androgenic ratios of the nandrolone esters continued to increase after the minimum, as the series ascended. This method is believed to give a reliable assessment of anabolic and androngenic activities of steroid esters.
A sensitive biological assay for prostaglandin E and acetylcholine
Authors: Vapaatalo H , Lindén Inge-Britt , Parantainen J
Published: April 2011

Superfused hamster stomach strip has been used in the bioassay of prostaglandin E2 (PGE2) and acetylcholine. The preparation proved very stable and had no spontaneous movements. The sensitivity to PGE2 (and PGE1) was in the range of 10−9 gml−1 and to acetylcholine 10−12 g ml−1. After treatment with physostigmine the sensitivity to acetylcholine was 10−15 g ml−1. In acetylcholine determination the preparation is more sensitive than any other method.
Preliminary investigations of the metabolism and pharmacological activity of β-hydroxytryptamines in mammals
Authors: PlavšIč V , Iskrić S , Kveder S , Tućan-Foretić M , Wolf D , Gjuriš V , Supek Z
Published: April 2011

β-Hydroxytryptamine and β-hydroxy-5-hydroxytryptamine were incubated with rat liver slices and oxidative deamination was established as the main route of metabolism: in both instances the corresponding indole-3-glycollic acids and indole-3-ethane diols were the major metabolites. However, the rates of deamination of β-hydroxylated tryptamines, as measured manometrically, were found to be much slower than those of tryptamines non-hydroxylated in the side chain. The pharmacological activities of β-hydroxylated tryptamines were tested in guinea-pigs on resistance of respiratory pathways, spontaneous respiration, electrocardiogram, blood pressure and isolated ileum, using tryptamine and 5-HT as reference substances. The effects of tryptamines hydroxylated in the side chain were in general similar to those of corresponding tryptamines but of much lower intensities; only in increasing the blood pressure was β-hydroxytryptamine as active as tryptamine. The different reactions of these two groups of substances in the presence of some antagonists indicate that the receptors are probably not the same.
An in vitro method for the study of β-receptor mediated effects on slow contracting skeletal muscle
Authors: Waldeck Bertil
Published: April 2011

The soleus muscle of a guinea-pig was dissected out under pentobarbitone anaesthesia and mounted on a holder in an organ bath containing Krebs solution. The tendon was attached to a force transducer and subtetanic contractions were evoked by electrical field stimulation (0·5 ms pulses at 10·12 Hz for 1·5 or 3 s every 22 s). The experiments were performed at 37°. Terbutaline, a selective agonist at β2-adrenoceptors, reduced the force of subtetanic contractions in a dose-dependent manner, the EC50 being 0·2 μm. The reduction was due to a lessened degree of fusion. The results conform to previous in vivo studies.
Effects of paraffin coatings on the tensile strength of lactose
Authors: IRONO CECILIA I , PILPEL N
Published: April 2011

Measurements have been made of the tensile strength of lactose at different temperatures after coating it with up to 10−4 mol of various paraffin hydrocarbons g−1 of powder. Providing the coating is in a liquified form, either as a result of the ambient temperature or because of the localized high pressure at the points of true contact between the particles, there is a correlation between the tensile strength of the powder and the thickness and viscosity of the coating layer.
A stability-indicating assay for cefotaxime utilizing thin-layer chromatography with fluorescence detection
Authors: FABRE H , HUSSAM-EDDINE N
Published: April 2011

A t.l.c. method on silicagel plate with a fluorescence indicator has been carried out to increase the native fluorescence of cefotaxime and four of its degradation products. A simultaneous improved fluorimetric quantitation of the compounds in situ is proposed using a chromatogram spectrophotometer. The detectability (0.20 μg) shows that the procedure is twenty times more sensitive than high-pressure liquid chromatography with u.v. detection; it allows the determination of traces level (1%) degradation products.
Effect of the triazolobenzodiazepine estazolam on hepatic drug-metabolizing enzyme activity in rats
Authors: DOWN W H , HAWKINS D R , CHASSEAUD L F
Published: April 2011

Oral doses of the sedative/hypnotic estazolam (500 mg kg−1 day−1) to rats for 21 days caused statistically significant increases in liver weight, ascorbate excretion, cytochrome P-450 concentrations, and in aniline hydroxylase, ethylmorphine N-demethylase and glutathione S-transferase activities, as did approximately equivalent doses of flurazepam hydrochloride. Histologically, the centrilobular hepatocytes were enlarged. Some of these parameters were also increased after doses of estazolam of 100 mg kg−1 day−1, but not after 5 mg kg−1 day−1, which is about 50-fold greater than a clinical dose. Estazolam was a much less potent enzyme inducer than phenobarbitone under the conditions of these studies.
Stereospecific inhibition of oxotremorine-induced antinociception by (+)-isomers of opioid antagonists: comparison with opioid receptor agonists
Authors: BEN-SRETI M M , SEWELL R D E
Published: April 2011

The antagonistic effects of the two benzomorphan opioid antagonists, Mr-1452 and Mr-2266 and their respective (+)-isomers Mr-1453 and Mr-2267 upon morphine, ethylketocyclazocine (EKC), D-ala2-D-leu5–enkephalinamide (BW 180-C) and oxotremorine (OTMN) antinociceptive activity in mice were investigated. Pretreatment with either Mr-1452 (2.0 mg kg−1 i.p.) or Mr-2266 (2.0 mg kg−1 i.p.) significantly antagonized the antinociceptive effects of the three opioid agonists in the hot plate test, but were ineffective against OTMN, which in contrast was antagonized by the (+)-isomers. Interaction between the antagonists and submaximal analgesic doses of the opioids or OTMN produced similar results in the tail immersion assay. However, the effect of Mr-2267 on OTMN was biphasic and this contrasted with Mr-1453 which produced consistent and graded antagonism.
Release kinetics of sparingly soluble drugs from ethyl cellulose-walled microcapsules: salicylamide microcapsules
Authors: DONBROW M , BENITA S
Published: April 2011

Release rates of salicylamide from single-core ethyl cellulose (EC) coated microcapsules were measured as a function of wall thickness and core particle size. Whereas up to ca 50% release zero order kinetics were observed, the overall reaction fitted the first order and Higuchi matrix treatment. These were distinguished by the differential rate treatment, which showed that the overall release in fact followed the first order pattern. For investigating whether the process was membrane-controlled, the experimental rate constants were transformed into effective permeability constants (P0 and P1 with the aid of the microcapsule dimensional parameters needed in the relevant equations and compared with the salicylamide permeability constant for planar ethyl cellulose membranes (P), measured experimentally. P0 and P1 values obtained for a given microcapsule preparation were not identical: P0 was of the same order as P, P1 being much lower. While membrane-controlled release is evident, it is apparently accompanied by a first order concentration gradient change inside the microcapsule.
The effect on the rat isolated atria of amiodarone in the presence of either ouabain or verapamil
Authors: Bowles B J M , Pleuvry B J , Healy T E J
Published: April 2011

Amiodarone causes a decrease in the rate of contraction of the rat isolated atria and has a negative inotropic action in the paced preparation. Interactions occur between amiodarone and oubain and amiodarone and verapamil. It is possible that the clinically reported drug interaction with amiodarone may have a component of direct interactions on the myocardium rather than solely changes in plasma protein binding.
Studies of carbon-13 n.m.r. spectroscopy in pharmaceutical analysis: the composition of commercial samples of gentamicin sulphate
Authors: Kountourellis J , Parfitt R T , Casy A F
Published: April 2011

Two procedures for applying 13C n.m.r. spectroscopy to the quantitative analysis of the C1 C1a, and C2 components of gentamicin sulphate samples are described. One is based on the use of calibration plots of peak height ratios of analyte to standard (dioxan) resonance intensities recorded under conditions of full relaxation, the other upon a steady-state experiment and the use of weighting factors. Spectrometer operating conditions are discussed, and the need for measurement of longitudinal relaxation time (T1) data described. Results for seven commercial samples are given and comparisons made between the two n.m.r. methods and an h.p.l.c. procedure in terms of accuracy, specificity and convenience.
Penetration of nabumetone into inflammatory exudates in the rat
Authors: Haddock R E , Jeffery D J , Mangan F R , Pardon I S
Published: April 2011

The penetration of radioactivity into inflamed sites induced by subcutaneously implanted cotton pellets was studied in the rat after oral administration of [14C]nabumetone. Equilibration between inflamed site and plasma concentrations was slow, maximum concentrations in the pellet granuloma being later than those in the plasma. Nabumetone itself was found only in very low concentrations at the inflamed site and was not found in plasma. The major component (70%) of the radioactivity at both sites was the metabolite 6-methoxy-2-naphthylacetic acid, a compound which has anti-inflammatory properties. Elimination of radioactivity from the plasma and inflamed site was virtually complete within 24 h of dosing. Daily dosing with [14C]nabumetone confirmed that there was no progressive accumulation of radioactivity at the inflamed site.