bluuebunny/crossref_metadata_2025 huggingface dataset:
The antimicrobial efficiencies of contact lens solutions
Authors: Norton D A , Davies D J G , Richardson N E , Meakin B J , Keall A
Published: April 2011

The antimicrobial efficiencies of 34 commercially available contact lens solutions has been tested against Pseudomonas aeruginosa, Staphylococcus aureus, Micrococcus luteus and Candida albicans. A standard inoculum of 106 organisms ml−1 was placed in a sample of a contact lens solution and samples taken at various times up to 48 h. These were placed in a recovery medium and the presence or absence of growth noted after 48 h incubation at 37°. Of 14 solutions used to soak and disinfect lenses only 4 inactivated all four test strains within 1 h, 7 within 4 h, while 6 solutions allowed growth of one or more test organisms even after 24 h contact. Of the remaining 20 solutions, with their various functions such as cleaning and wetting of lenses, 13 failed to inhibit one or more test strains after 24 h contact. Some form of control of the manufacture and presentation together with minimum standards of antimicrobial efficiency would seem to be desirable.
Some solution properties of pentagastrin and angiotensin: aggregation of pentagastrin
Authors: Attwood D , Florence A T , Greig Rosemary , Smail G A
Published: April 2011

Pentagastrin and angiotensin have been studied in the presence and absence of urea by light-scattering, viscosity, dialysis, surface tension and other physicochemical techniques for evidence of peptide aggregation. Pentagastrin forms large linear, flexible aggregates (molecular weight 40 000) in phosphate buffer above a concentration of ∼0·1 g dl−1 and in solutions shows time-dependent flow behaviour. Angiotensin shows no evidence of aggregation beyond dimers. In 1m urea the pentagastrin is in the form of dimers.
An analogue computer simulation of drug dissolution
Authors: Collett J H , Rees Judith A
Published: April 2011

The dissolution rate of salicylic acid from non-disintegrating discs at controlled pH has been determined. A theoretical model of dissolution has been developed in terms of the diffusion layer theory. This model has been programmed on an analogue computer and theoretical dissolution curves have been obtained. Experimental dissolution curves have been compared with simulated curves and the fit of the data has allowed the estimation of drug concentration in the diffusion layer.
An ESR titration technique for the determination of accessible tyrosine and tryptophan residues in globular proteins
Authors: Cloughley J B , Hooper M , Maxwell J
Published: April 2011

The reaction of potassium nitrosyldisulphonate (NDS) with globular proteins has been monitored by electron spin resonance. The reaction is shown to be sufficiently sensitive and reproducible to provide a rapid new method for the estimation of exposed tyrosine and tryptophan residues in these proteins at physiological pH. Under these conditions each tyrosine residue was found to consume 2 moles, and each tryptophan residue 3 moles, of NDS. The estimation of accessible groups thus obtained are in good agreement with published data obtained using other chemical probes.
A gas chromatographic determination of carbenoxolone in human serum
Authors: Rhodes C , Wright P A
Published: April 2011

A gas-liquid chromatography procedure for the determination of carbenoxolone in human serum is described. The method showed a better than ± 11% coefficient of variation for all values determined. The mean determined value is accurate to ± 10% of the known value for carbenoxolone over a range of 5 to 100 μg ml−1 serum. The specificity of the method was established by combining the gas-liquid chromatography analysis with thin-layer chromatography of prepared standards and serum from treated volunteers. The method is suitable for routine pharmacokinetic and bioavailability studies of carbenoxolone in serum and other biological fluids and supersedes previous methods in specificity, sensitivity and simplicity of determination.
The binding of sulphonylureas to serum albumin
Authors: Crooks M J , Brown K F
Published: April 2011

The interaction of tolbutamide, glibenclamide, chlorpropamide and tolazamide with serum albumin has been examined. Glibenclamide, the most strongly bound of the four compounds, is bound to only one class of sites. The other three compounds are bound to at least two. The interaction between glibenclamide and albumin was independent of pH and increased markedly with decreasing temperature suggesting that a non-ionic mechanism is involved. In contrast, the overall interaction of tolbutamide with albumin showed little temperature dependence and, in addition, binding of both tolbutamide and chlorpropamide decreased with pH. These findings imply that the predominantly bound species is the anion. Binding parameters corrected for electrostatic effects were found to fit binding data for tolbutamide, chlorpropamide and tolazamide better than uncorrected parameters. Electrostatic correction of binding of glibenclamide is unnecessary.
The structure of nitrones derived from amphetamines
Authors: Beckett A H , Coutts R T , Ogunbona F A
Published: April 2011

The nitrones obtained by mercuric oxide oxidation of N-hydroxy-N-n-propylamphetamine and N-ethyl-N-hydroxyamphetamine have been identified. The major in vitro metabolic product of fenfluramine is shown by a nuclear magnetic resonance study to be α-methyl-N-[1-(m-trifluoromethylbenzyl)ethyl]nitrone and not the isomer as claimed previously (Beckett, Coutts & Ogunbona, 1973a).
Distribution of exogenous acetaldehyde in cow adrenal medulla chromaffin granules
Authors: Schneider F H
Published: April 2011

Release of catecholamines from the cow perfused isolated adrenal gland was induced by infusion of acetaldehyde in concentrations between 5 times 10−4 and 3·5 times 10−1m. There was a significant correlation between the concentration of acetaldehyde and catecholamine release. Analysis of homogenates of medullae from glands stimulated with [14C]acetaldehyde showed that the specific activity (14C mg−1 protein) was higher in chromaffin vesicles than in other tissue fractions. The major portion of the 14C of chromaffin vesicles was present as soluble tetrahydroisoquinoline derivatives. There was no correlation between catecholamine release and the amount of tetrahydroiso-quinolines formed. A small portion of the vesicle 14C was associated with the membrane, and there was a significant correlation between the membrane-bound 14C and catecholamine release. It is concluded that acetaldehyde can interact with the chromaffin vesicle membrane in a way that alters the ability of the vesicle to retain catecholamines which then diffuse out of the vesicle and into the circulation.
The effect of monoamine oxidase inhibitors on the rectal temperature of the rat
Authors: Summers R J
Published: April 2011

The monoamine oxidase (MAO) inhibitors, clorgyline, harmaline, nialamide, phenelzine and tranylcypromine, injected intraperitoneally into conscious unrestrained rats produced hypothermia. When clorgyline and tranylcypromine were compared, the latter produced a larger degree of hypothermia in spite of the fact that both drugs almost completely inhibited liver and hypothalamic MAO. Hypothermia produced by tranylcypromine, but not that produced by clorgyline, was attenuated by prior administration of haloperidol which indicated that it was partly mediated by a dopaminergic mechanism. In addition, tranylcypromine, but not clorgyline, inhibited uptake of (–)-noradrenaline into rat hearts. Hypoglycaemia was not involved in the hypothermia produced by these MAO inhibitors in rats.
Effect of serum albumin upon the response of the rat isolated superfused anococcygeus muscle to catecholamines and to nerve stimulation
Authors: Powis G
Published: April 2011

The presence of bovine serum albumin in the superfusing medium reduced the response of the rat isolated anococcygeus muscle to catecholamines and to nerve stimulation. It is suggested that this is a consequence of the binding of catecholamines to serum albumin. When the binding was prevented, either by decreasing the pH or by the addition of a drug such as oxytetracycline, then the inhibitory effects of serum albumin were much reduced.
Spectrophotometric determination of ampicillin sodium in the presence of its degradation and polymerization products
Authors: Bundgaard Hans
Published: April 2011

A spectrophotometric method is described for the quantitative determination of ampicillin sodium [sodium salt of 6-(d(–)-phenylacetamido) penicillanic acid]. The method involves acetylation of ampicillin with acetic anhydride in aqueous solution at pH 9 to yield α-acetamido benzylpenicillin and subsequent measurement at 325 nm of α-acetamidobenzylpenicillenic acid mercuric mercaptide, formed in a quantitative yield on heating for 30 min at 60° in a 1·0m imidazole and 8 times 10−4m mercuric chloride solution at pH 6·8. It has been demonstrated that degradation products do not interfere in the method whereas those di- and polymerization products of ampicillin which contain an intact β-lactam ring are capable of reacting with imidazole with the formation of penicillenic acid. A technique involving acid-catalysed opening of the β-lactam ring of these products under conditions where ampicillin is degraded to only a minor extent has been developed, and besides permitting a selective determination of ampicillin the technique permits the determination of the polymeric substances.
The influence of porosity upon the distribution of reserpine in calcium sulphate granules
Authors: Nicholson G L , Enever R P
Published: April 2011

Batches of calcium sulphate granules, all of the same size fraction but of widely differing porosities, were prepared from primary granules of different sizes. Each batch was coated with reserpine by spraying a solution of the drug in methylene chloride onto the granules whilst they were tumbled in a coating pan. The relation between the macroporous nature of the granules and their reserpine content was investigated. Low-pressure mercury porosimetry was used to obtain a quantitative estimate of the porosity and macropore size distribution of the granules, and their surface areas were determined by an air permeability method. Linear relations were obtained when the reserpine content was plotted against either the volume of mercury penetrating per gram of granules at 106·5 kN m−2 or their surface area.
The response of isolated cardiac muscle to acute anoxia: protective effect of adenosine triphosphate and creatine phosphate
Authors: Parratt J R , Marshall R J
Published: April 2011

A standardized and reproduceable preparation is described that enables the effect of drugs to be examined on the response of isolated cardiac muscle to acute anoxia. There was a linear relation (r = 0·963) between tension developed in isolated, electrically-driven guinea-pig atria and the oxygen tension of the fluid surrounding the muscle. For any one atrial preparation the time taken, from the beginning of the anoxic period, for tension to be reduced by 50 % was constant for consecutive anoxic periods. ATP and creatine phosphate significantly increased this time and protected cardiac muscle against the consequences of anoxia; in concentrations that were without direct cardiac effects, a greater degree of protection was possible with creatine phosphate.
Effect of a sea snake (Enhydrina schistosa) venom on the ganglionic nicotinic actions of acetylcholine
Authors: Yeoh Peng N , Walker M J A
Published: April 2011

The effects of venom from a common sea snake, Enhydrina schistosa, on the actions of acetylcholine in the superior cervical ganglion, the adrenal medulla and in the atropinized cat were investigated. The crude venom reduced nictitating membrane responses to preganglionic nerve stimulation and intra-arterial injection of acetylcholine, without lowering the responses to postganglionic nerve stimulation or intra-arterial adrenaline. In the eviscerated cat, the venom also antagonized rises in heart rate and blood pressure induced by in-injections into the coeliac artery of acetylcholine but not those of histamine. Pressor effects due to splanchnic nerve stimulation and carotid artery occlusion were blocked. In the atropinized cat, the venom depressed heart rate and pressor responses to intravenous acetylcholine, but not the responses to adrenaline. It was concluded that the venom antagonized the actions of acetylcholine at autonomic ganglia and the adrenal medulla.
Inhibition by non-steroidal anti-inflammatory agents of the release of rabbit aorta contracting substance and prostaglandins from chopped guinea-pig lungs
Authors: Fjalland B
Published: April 2011

The release of prostaglandins (PGs) and rabbit aorta contracting substance (RCS) was investigated using mechanical agitation of chopped lung tissue from unsensitized guinea-pigs. Manual stirring of the lung tissue for 45 s produced maximal release of prostaglandins, a release corresponding to the effect of [20–40 ng ml−1 of PGE2 x 45 s at 5 ml min−1] about 100 ng PGE2 on the rat stomach strip. Nonsteroidal anti-inflammatory agents inhibited the release of the contracting substances. Indomethacin, the most potent, was active in concentrations of about 20 ng ml−1, whereas flufenamic acid was twice, phenylbutazone about 60 times, acetylsalicylic acid 100 times and sodium salicylate about 6000 times less active than indomethacin. The method could prove to be a simple test for screening nonsteroidal anti-inflammatory agents for inhibition of prostaglandin synthesis.
Effect of some β-adrenoceptor blocking drugs on insulin secretion in the rat
Authors: Furman B L , Tayo F M
Published: April 2011

In pentobarbitone anaesthetized rats (±)-propranolol reduced the stimulatory effect of glucose, sulphonylureas, isoprenaline or phentolamine on insulin secretion. (+)-Propranolol produced similar effects to those produced by the racemate. Sotalol reduced only the insulin secretion stimulated by isoprenaline or phentolamine but not that stimulated by glucose or sulphonylureas. Complete inhibition of isoprenaline-induced hyperinsulinaemia was obtained with practolol, in a dose which was without effect on the plasma insulin elevations produced by glucose or glibenclamide. (±)-Propranolol inhibited glucose or tolbutamide-stimulated insulin secretion from chopped pancreas in vitro indicating a direct action of the drug on the pancreas. It is suggested that propranolol-induced inhibition of insulin secretion may not be entirely due to the β-adrenoceptor blocking activity of the drug.
The effect of 6-hydroxydopamine on the oestrus cycle and fertility of rats
Authors: MacDonald E J , Airaksinen M M
Published: April 2011

Increases in the numbers of foetuses resorbed and stillborn are reported in rats after treatment with 6-hydroxydopamine given before and during pregnancy. 6-Hydroxydopamine (100 mg kg−1 i.p.) given before mating had no effect on the oestrus cycle. Intrahypothalamic 6-hydroxydopamine (200 μg) produced a temporary loss of oestrus. However, after mating the injected rats had normal pregnancies despite substantially lower levels of brain noradrenaline.
Inhibition of the mitochondrial oxidation of octanoate by salicylic acid and related compounds
Authors: Graham A B , Park M V
Published: April 2011

The inhibition of mitochondrial octanoate oxidation in vitro by salicylic acid (1mm), 2,4-dinitrophenol (0·05mm) and γ-resorcylic acid (2mm) was studied. Concentrations of salicylate and 2,4-dinitrophenol markedly inhibiting the mitochondrial oxidation of octanoate did not significantly affect the mitochondrial oxidation of octanoylcarnitine. All three compounds (0·4mm) inhibited a partially purified preparation of medium chain-length acyl-CoA synthetase from ox liver mitochondria. It is suggested that at least part of the ininhibition of mitochondrial oxidation by salicylic and γ-resorcylic acids in vitro in the concentration ranges studied is caused by the direct inhibition of the medium chain length acyl-CoA synthetase.
Influence of an acetylsalicylic anhydride impurity on the rate of dissolution of acetylsalicylic acid
Authors: Bundgaard Hans
Published: April 2011

The intrinsic dissolution rate of acetylsalicylic acid in 0·1 n hydrochloric acid at 35° has been shown by a rotating disc method to be affected by the presence of acetylsalicylic anhydride in the crystals. At concentrations exceeding 0·25% the impurity decreased the dissolution rate of the acetylsalicylic acid. It is suggested that the previously reported differences in rates of dissolution of various commercial and recrystallized acetylsalicylic acid preparations may be due to differences in content of acetylsalicylic anhydride which is a frequently-occurring impurity in commercial acetylsalicylic acid and is formed on heating solutions of acetylsalicylic acid in various organic solvents.
Phase studies of mixed phosphated surfactants, n-hexane and water
Authors: Groves M J , Mustafa R M A , Carless J E
Published: April 2011

Mixtures of phosphated nonylphenolethoxylate (PNE), phosphated fatty alcohol ethoxylate (PFE) and n-hexane form ‘oils’ which may spontaneously emulsify when added to water. However, the degree of spontaneity and the stability of the resulting dispersions vary according to the constitution of the system. Studies of the equilibrium phase diagrams suggest that the anomalies may be attributed to the presence of liquid crystalline phases of different types which are formed in the presence of water.
Computer analysis of multicomponent ultraviolet spectra
Authors: Madsen B W , Herbison-Evans D , Robertson J S
Published: April 2011

In the assay of multicomponent systems by ultraviolet spectrophotometry, it is possible to improve accuracy and precision and also to obtain various statistical criteria by considering data over the range of wavelengths concerned. A linear least squares approach has been programmed to analyse mixtures of drugs in the presence or absence of known background. When the background was unknown but could be assumed of simple form, a non-linear alternative was successful.
Mechanism of induction of hepatic microsomal drug metabolizing enzymes by a series of barbiturates
Authors: Ioannides Costas , Parke Dennis V
Published: April 2011

The inducing effect of certain barbiturates (secobarbitone, thiopentone, pentobarbitone, allobarbitone, phenobarbitone and barbitone) on the levels of the hepatic microsomal drug-metabolizing enzymes has been studied in the rat both in vivo and in vitro. The extent of induction was related to the plasma half-lives of the barbiturates; compounds with low rates of metabolism and long half-lives were the most potent inducing agents. The latter (phenobarbitone, pentobarbitone and allobarbitone) were shown by spectral technique to interact with cytochrome P-450 suggesting that their mechanism of enzyme induction was ‘substrate induction’ in type. Barbiturates containing an allyl group (secobarbitone and allobarbitone) had a weaker inducing effect than expected, possibly due to their destruction of cytochrome P-450. Despite its short plasma half-life of 0·5 h thiopentone was a relatively potent inducer probably due to its metabolism to pentobarbitone, which has a much longer plasma half-life (1·3 h). Barbitone is an effective inducer of the drug-metabolizing enzymes, yet does not interact spectrally with cytochrome P-450; this is in accord with the observations that although there are increases in NADPH-cytochrome c reductase and cytochrome b5, following administration of barbitone there is no increase in cytochrome P-450. Barbiturate pretreatment does not affect the activities of glucose-6-phosphatase, glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase.
The influence of polyvinylpyrrolidone on the dissolution properties of hydroflumethiazide
Authors: Corrigan O I , Timoney R F
Published: April 2011

The incorporation of hydroflumethiazide with polyvinylpyrrolidone (PVP) was found to retard and to enhance the dissolution of the drug from compressed discs, the magnitude of the effect being dependent on the proportion of PVP present and its method of incorporation. The most active system dissolved sixteen times faster than pure hydroflumethiazide. Low concentrations of PVP were also found to decrease the apparent solubility of hydroflumethiazide while at high concentrations solubility was enhanced. X-ray and infrared analysis of systems suggested the presence of an amorphous form of hydroflumethiazide in coprecipitate systems. The dissolution data were consistent with a physical model which takes account of the roles played by crystalline and amorphous hydroflumethiazide together with the complexing and crystal growth inhibiting effect of PVP on hydroflumethiazide.
Effects of hardness on the disintegration time and the dissolution rate of uncoated caffeine tablets
Authors: Kitazawa Shikifumi , Johno Ikuo , Ito Yoko , Teramura Shigeo , Okada Jutaro
Published: April 2011

The effects of hardness on disintegration and dissolution characteristics of uncoated caffeine tablets made at eight different pressure levels were studied. The disintegration times were determined using the J.P. VIII procedure with disks and the dissolution rate measurements were performed with the U.S.P. XVIII procedure (U.S.P. method) and the J.P. VIII disintegration test apparatus (J.P. method). A good correlation between the hardness and the disintegration times was obtained. The dissolution rate constants were determined from the equation of Noyes & Whitney (1897) and a good correlation between the hardness and the dissolution rate constants was obtained. The hardness governed the dissolution over all the stages from tablet to the smallest particles after the breakage by disintegration. The dissolution rates of the J.P. method were greater than those of the U.S.P. method.
Some effects of pilocarpine and acetylcholine on the responses of the guinea-pig vas deferens to hypogastric nerve stimulation and transmural stimulation and applied (–)-noradrenaline
Authors: Lamble Andrea P , Lamble J W
Published: April 2011

Enhancement by acetylcholine and by pilocarpine of the contractile responses of the guinea-pig isolated vas deferens to hypogastric nerve and transmural stimulation and to exogenous (–)-noradrenaline was examined. At high concentration (600 nm) acetylcholine enhanced responses in the order: hypogastric nerve > transmural > exogenous (–)-noradrenaline. Pilocarpine produced a similar maximal degree of enhancement with all three stimuli. All these effects were reversibly inhibited by 1.4 μta atropine, a concentration which alone did not affect responses to the stimuli. Pilocarpine (50–400 μm) gave a concentration-related inhibition of the enhancement of responses to hypogastric nerve stimulation by 600 nm acetylcholine.
The pharmacology of Avena sativa
Authors: Connor J , Connor T , Marshall P B , Reid A , Turnbull M J
Published: April 2011

The pharmacology of Avena sativa has been investigated in laboratory animals following a report that tincture of Avena sativa reduced the craving for cigarettes in man. The tincture, evaporated to dryness, re-constituted in an equal volume of water and administered by stomach tube or intraperitoneal injection, antagonized the antinociceptive effect of morphine in two separate tests (hot-plate and tail flick). Compared with animals made dependent on morphine alone, mice pretreated with repeated injections of morphine plus extract passed a smaller number of stools and tended to jump less after administration of nalorphine. The pressor response to intravenously administered nicotine in urethane-anaesthetized rats was also antagonized by prior administration of Avena sativa. However, the aqueous extract prepared from the tincture did not affect the seizure threshold to bemegride or nicotine or the sleeping time induced by barbitone sodium.
Effects of a human plasma fraction on leucocyte migration into inflammatory exudates
Authors: Ford-Hutchinson A W , Smith M J H , Elliott P N C , Bolam J P , Walker J R , Lobo A A , Badcock J K , Colledge A J , Billimoria F J
Published: April 2011

A fraction prepared from normal human plasma inhibits the migration of polymorphonuclear and mononuclear leucocytes into inflammatory exudates produced by the intrapleural injection of carrageenan or turpentine and by the subcutaneous implantation of polyvinyl sponges in the rat. The mechanism of the effect does not involve complement depletion.
Effect of pregnenolone-16α-carbonitrile (PCN) on drug response in man
Authors: Szabo S , Komlos S , Ignjatovic Z
Published: April 2011

Pregnenolone-16α-carbonitrile (PCN), which alters drug responses and induces hepatic microsomal drug-metabolizing enzymes in experimental animals, is well-tolerated in man. There were no marked changes in the concentrations of blood sugar and urea; bromsulphophthalein (BSP) clearance; serum alkaline phosphatase activity; hematocrit, erythrocyte and leukocyte counts; as well as in ecg patterns. When the steroid was given by mouth for 4 days to patients treated with electroshock for psychiatric disorders, it decreased suxamethonium-induced skeletal muscle fasciculation and shortened thiopentone as well as propanidid anaesthesia. Breathing was resumed more rapidly than in control subjects. The protective effect of PCN is probably mediated through induction or activation of hepatic drug-metabolizing enzymes, or both.
The solubilization of some local anaesthetic esters of p-aminobenzoic acid by lysophosphatidylcholine
Authors: Hunt M J , Saunders L
Published: April 2011

The solubilization by lysophosphatidylcholine (LPC) of three n-alkyl esters of p-aminobenzoic acid has been studied. These esters have a local anaesthetic action. Quantitative studies show that the amount of compound solubilized is proportional to the LPC concentration and that solubilization increases in the order ethyl, n-propyl and n-butyl ester. 100MHz nmr studies indicate that the local anaesthetic esters are solubilized in the hydrocarbon interior of the LPC.
The influence of cosolvents and substrate substituents on the sorption of benzoic acid derivatives by polyamides
Authors: Richardson N E , Meakin B J
Published: April 2011

The sorption of some substituted benzoic acid derivatives by polyamides (nylons) from aqueous solution has been examined and the influence of their nature together with those of the cosolvent and polymer have been assessed. In all cases the sorption isotherms were linear and could be expressed by a simple distribution law, enabling the influence of cosolvent concentration to be predicted. The sorption of a series of p-substituted benzoic acids and some of their esters is related to their solubility except where the p-substituent is capable of hydrogen-bonding with the polymer. The extent of the interaction is also dependent upon the amide frequency of the polymer.
Isolation, characterization and quantitation of chloral hydrate as a transient metabolite of trichloroethylene in man using electron capture gas chromatography and mass fragmentography
Authors: Cole W J , Mitchell Rosemary G , Salamonsen R F
Published: April 2011

A method for the quantitative determination of plasma concentrations of chloral hydrate by electron capture gas chromatography is described. Characterization by multiple ion monitoring confirms, for the first time, that chloral hydrate exists as a transient metabolite of trichloroethylene in man.
Comparison of the time course of the anorectic effect of fenfluramine and amphetamine with drug levels in blood
Authors: Blundell J E , Campbell D B , Lesham M , Tozer R
Published: April 2011

Time courses of the suppressive effects on food intake of (+)-amphetamine and (±)-fenfluramine in deprived rats were found to be different. Amphetamine displayed a potent initial action which rapidly decayed, and this behavioural effect was consistent with the measured blood concentration of amphetamine which showed a peak at 1 h followed by rapid clearance. For fenfluramine, the initial suppression of eating was maintained over several hours and was, for the first hour, related to the blood concentration of fenfluramine but later to an active metabolite, norfenfluramine. The study shows how drug-induced changes in feeding behaviour fluctuate over time and illustrate how single measures of food intake may overlook information about the effectiveness of anorectic drugs.
How does angiotensin II increase cardiac dopamine-β-hydroxylation?
Authors: Chevillard Claude , Duchene Nicole , Alexandre Jean Michel
Published: April 2011

The potent accelerating effect of angiotensin II (Ang II) on cardiac dopamine β-hydroxylation was studied on slices of rat heart. Ang II did not affect the kinetics of β-hydroxylation but it increased the axonal uptake of dopamine, and, concomitant with the acceleration of biosynthesis, it enhanced the accumulation of dopamine into tissue. Puromycin, in contrast to actinomycin D, antagonized the stimulation of dopamine β-hydroxylation by Ang II, but did not suppress the rise in cardiac dopamine. Therefore, to promote the acceleration of dopamine β-hydroxylation, (i) the rise in tissue dopamine available for conversion appeared to be insufficient, (ii) the formation of new proteins by activation of traduction seemed to constitute the basic mechanism of Ang II action.
Some relations between dissolution rates and physical parameters of a drug in aqueous micellar solutions of a non-ionic surfactant
Authors: Collett J H , Rees Judith A
Published: April 2011

Dissolution rates of salicylic acid from a constant surface area into a series of aqueous micellar polysorbate 20 solutions at pH 1·0 to 4·0 have been measured using two different methods; a stirred beaker and a rotating disc technique. The micellar molecular weight of polysorbate 20 has been obtained from light scattering and differential refractometry data and used with other independently determined physical data to calculate diffusion coefficients of the diffusing species. Linear multiple regression analysis was used to assess the dependence of drug dissolution rate on the diffusion coefficient and the viscosity of the dissolution medium.
The effect of ageing on the rheological properties of gelatin gels
Authors: Robinson John A J , Kellaway Ian W , Marriott Christopher
Published: April 2011

The effect of ageing at 4° on the viscoelastic properties of 1·5 and 2·0% acid and alkaline processed gelatin gels has been investigated. Viscoelastic properties were not markedly affected by ageing time although evidence of a decrease in gel structure with increasing ageing time was apparent. This has been tentatively attributed to hydrolysis of amide links. 1·5% alkaline gels were shown to be more rigid than the corresponding acid gels and this has been discussed in terms of differences in molecular weight, polydispersity, charge and charge distribution.
Locomotor activity stimulation in rats produced by dopamine in the nucleus accumbens: potentiation by caffeine
Authors: Andén Nils-Erik , Jackson David M
Published: April 2011

The increased motor activity of reserpine-nialamide pretreated rats given dopamine into the nucleus accumbens was potentiated in a dose-dependent manner by systemically administered caffeine. Similarly, the increase in motor activity seen when the endogenous dopamine was released by intraperitoneally administered amphetamine was potentiated by systemically given caffeine. These effects might be due to an increase in the dopamine-induced accumulation of cyclic AMP in the nucleus accumbens after inhibition of the phosphodiesterase by caffeine.
The in vitro adsorption of drugs from horse serum onto carbon coated with an acrylic hydrogel
Authors: Kolthammer J
Published: April 2011

In vitro studies have shown that uncoated carbon and carbon coated with an acrylic hydrogel are capable of adsorbing drugs from horse serum at 37°. Increase in the coating weight from 2 to 4% decreased the rate of adsorption but not the total capacity. In vivo data supports the concept of carbon haemoperfusion for use in the treatment of drug overdose.
Inhibition of drug-induced anorexia in rats by methysergide
Authors: Barrett A M , McSharry Lesley
Published: April 2011

Iproniazid was found to reduce food consumption in fasting rats. Combined treatment of iproniazid with tryptophan resulted in a significantly greater anorexic action whilst tryptophan alone had no effect on food consumption. Iproniazid treatment was associated with a significant increase in brain 5-hydroxytryptamine (5-HT) concentration but in association with tryptophan higher brain 5-HT concentrations were recorded. The anorexic action of the iproniazid-tryptophan combination was antagonized in a dose-dependent fashion by methysergide. Equivalent levels of anorexia induced by fenfluramine and mazindol were similarly antagonized by methysergide in a dose-related manner. The results suggest a common role of 5-HT in the inhibition of eating behaviour in fasting rats when anorexia is induced by iproniazid, fenfluramine or mazindol, sensitive to a specific 5-HT antagonist.
The effect of an aldosterone antagonist on the protective action of carbenoxolone on the gastric mucosal barrier
Authors: Rees W D W , Rhodes J , Cross S , Hole D
Published: April 2011

The effect of an aldosterone antagonist on the protective action of carbenoxolone sodium on the gastric mucosal barrier has been studied in three dogs with Heidenhain pouches. The net fluxes of hydrogen ion and sodium ion were measured before, during, and after contact with a 10 mm bile acid solution at pH 2, in pouches which had not been treated with drugs, in pouches treated with carbenoxolone sodium and in pouches treated with both carbenoxolone sodium and the aldosterone antagonist, spironolactone.

Hydrogen ion back diffusion from, and sodium ion gain by the untreated pouch was increased by 10 mm bile acid solution. Addition to the pouches of either carbenoxolone sodium alone or carbenoxolone sodium and spironolactone reduced the hydrogen ion back diffusion after exposure to the bile acid solution. The spironolactone did not change the protective effect of carbenoxolone on the gastric mucosal barrier. Carbenoxolone did not change the increased sodium ion diffusion caused by bile.
The bioavailability in man of ICRF-159 a new oral antineoplastic agent
Authors: Creaven Patrick J , Allen Larry M , Alford Dorothy A
Published: April 2011

The bioavailability of the antineoplastic agent, ICRF-159, has been examined in 12 patients receiving the drug in single and subdivided dose schedules in an attempt to account for the differences in toxicity found with the different schedules clinically. Recovery of radioactivity in the urine after single large doses (13·3–19·4 g) was 8·5 ± 3·0% of the administered dose. After doses of 3·8–5·55 g recovery was 22·7 10±5% and after the same dose subdivided into 3 equal aliquots it was 52 ± 8·7%. Unrecovered radioactivity was largely accounted for in the faeces. Plasma radioactivity levels in 2 patients after high and low dose were equivalent. Toxicity of the drug paralleled urinary recovery of radioactivity. It is concluded that schedule dependence of toxicity of ICRF-159 is at least partly due to bioavailability factors.
A rapid g.l.c. procedure for the determination of codeine and norcodeine in biological fluids based on micro-phase extraction techniques
Authors: Serfontein Willem J , Botha Deo , de Villiers Louis
Published: April 2011

Therapeutic serum concentrations of codeine can be virtually completely extracted and obtained sufficiently concentrated for g.c. measurement without distillation, by acid extraction of the drug from the initial crude organic extracts of alkalinized serum followed by a micro-phase back extraction step. The procedure has simplicity, rapidity and eliminates concentration by distillation and background interference. The method can be readily adapted for the separate measurement of codeine and norcodeine and it can also be used for similar analyses of other body fluids.
The determination of thebaine in Papaver bracteatum Lindl by gas-liquid chromatography
Authors: Fairbairn J W , Helliwell K
Published: April 2011

Several solvents have been examined in the process of developing a convenient method for extracting powdered material and removing interfering pigments to produce an extract of Papaver bracteatum suitable for g.l.c. assay. The most suitable extracting solvent was aqueous acetic acid (5%); the assay method gave satisfactory reproducibility with a wide range of plant materials (coefficient of variation 0.63 to 3.33 %). The accuracy was checked by recovery experiments with pure thebaine and by examination of exhausted marcs. The presence of other alkaloids did not interfere with the assay. There were substantial differences in the amounts of thebaine extracted from capsule and root samples by ammoniacal methanol and by aqueous acetic acid, indicating the presence of thebaine in a “bound” form. The minimum amount of thebaine that could readily be determined by the g.l.c. method was 0.3 mg in the sample of powder used for the assay.
A model for steroid transport across biological membranes
Authors: Beckett A H , Pickup M E
Published: April 2011

The absorption of a range of steroids (water soluble to lipid soluble) in the mouth was investigated under standard conditions and using gas chromatography. A two-compartment open model was used to describe the absorption of these steroids into, and through, the membrane. Rate constants were calculated on this basis using a feathering technique, and were used in an analogue computer program to predict steroid concentration which agreed favourably with experimental data. Correlations between absorption and partition data were made in an attempt to relate the proposed model to anatomical features of the absorptive membrane and to make comparison with models proposed to describe drug absorption across the intestinal mucosa.
Investigation of changes in the lipid content of guinea-pig lung after anaphylaxis
Authors: Goadby P
Published: April 2011

A detailed analysis of the lipid content of guinea-pig lung following anaphylaxis in vivo induced by aerosolized antigen snowed a significant reduction in all fractions. Anoxia induced by nitrogen produced reductions in the partial glycerides and ethanolamine phospholipid. Exposure to an aerosol of histamine caused a reduction in all but the choline phospholipid and sphingolipid fractions. It was concluded that the losses of choline phospholipid and sphingolipid result from the anaphylactic reaction and not from subsequent changes.
The effect of acute bilateral adrenalectomy on vasopressor responses to catecholamines in dogs
Authors: Chopde C T , Brahmankar D M , Sheorey R V , Udhoji A G , Dorle A K
Published: April 2011

The effect of acute bilateral adrenalectomy on the pressor responses to adrenaline, noradrenaline and isoprenaline was studied in anaesthetized dogs. The responses to all the three catecholamines were reduced by adrenalectomy. Treatment with cortisone, cyclic AMP partially restored the responsiveness. Desoxycorticosterone, aldosterone, hydrocortisone, phenylbutazone or infusion of either saline and noradrenaline failed to improve the impaired pressor responses seen in adrenalectomized dogs. Treatment with corticosterone alone, combined administration of aldosterone and hydrocortisone or cortisone followed by cyclic 3′,5′-AMP also restored catecholamine responses almost to normal. The pressor responses to catecholamines in dogs were also reduced by metyrapone-induced cortical insufficiency. Administration of corticosterone, cortisone or cyclic AMP slightly improved these responses; the recovery was not, however, as effective as that noted in the adrenalectomized condition.
Differences between the anorexic actions of amphetamine and fenfluramine—possible effects on hunger and satiety
Authors: Blundell J E , Latham C J , Leshem M B
Published: April 2011

The inhibition of feeding in rats brought about by amphetamine and fenfluramine was continuously monitored for periods of up to 24 h using a pellet detecting eatometer. For rats tested under conditions of food deprivation the two drugs gave rise to distinctive anorexic profiles: amphetamine delayed the onset of eating whereas fenfluramine allowed eating to commence normally but brought about an early termination of the initial bout of feeding. When the drugs were administered to rats with free access to food, analysis of the meal pattern showed that amphetamine gave rise to a small increase in the inter-meal interval while fenfluramine brought about a clear reduction in meal size. It is suggested that the contrasting modes of action of these drugs represent an effect of amphetamine upon hunger and an action of fenfluramine on satiety. This suggestion is in keeping with the proposed mechanisms of action of these drugs, amphetamine acting upon a hypothalamic motivational system and fenfluramine acting by means of a postulated serotoninergic satiety system. Use of the continuous monitoring technique has pointed to certain limitations in the assessment of anorexic drug action by means of discrete food sampling periods.
Adrenergic responses of the rabbit stomach serosal strip and their modification by monoamine oxidase inhibitors and anti-adrenergic drugs
Authors: Khayyal M T , Tolba Hedayat , El-Hawary M B
Published: April 2011

The rabbit stomach serosal strip, was found to contract to adrenaline and noradrenaline but not to isoprenaline. The contractile response could be totally abolished by phenoxybenzamine but was not influenced by propranolol, indicating that the preparation has almost exclusively α-adrenoceptors. The responses to adrenaline and noradrenaline were markedly potentiated in the presence of monoamine oxidase inhibitors, guanethidine or reserpine, indicating the presence of MAO activity in the tissue and possibly catecholamine stores. The functional state of the latter has not been conclusively established, since tyramine, an indirectly acting amine, was unable to elicit a response qualitatively similar to that of adrenaline, even in the presence of nialamide or tranylcypromine.
The influence of dihydroxyanthracene derivatives on water and electrolyte movement in rat colon
Authors: Lemmens L , Borja E
Published: April 2011

The purgative activities of 18 different dihydroxyanthracene derivatives, including free anthraquinones and anthrones, were investigated by determining their influence on the water, sodium and potassium absorption in the gastrointestinal tract by direct injection of the solutions in Tyrode to the rat colon in situ. The extent of the solubility of the compounds has also been assessed. The 1,8-dihydroxyanthracene structure seemed to be the best for hydragogue effect. Rhein-anthraquinone and -anthrone were the most active compounds tested.
A model independent method for estimating the in vivo release rate constant of a drug from its oral formulations
Authors: Vaughan D P
Published: April 2011

A simple equation by which the first-order release rate constant of a drug from its oral formulation can be calculated is derived. The derivation is independent of any hypothetical concepts of drug distribution or elimination.
The granulation of binary mixtures
Authors: Opakunle W O , Spring M S
Published: April 2011

Granules have been prepared from blends of lactose and boric acid by the massing and screening method and their properties have been compared with those of granules from the individual materials, granulated separately. Increasing the volume of binder solution used produced granules stronger and of greater mean size in all blends studied. The largest and strongest granules, for any given binder solution volume and massing time, were obtained from a blend, as were the granules with the minimum pore size. The effect of massing time on granule properties was generally similar to those already reported for single component systems; prolonged massing in some blends led to a reduction in mean granule size. Variation in pre-mixing time produced no significant change in the physical properties of granules prepared from a lactose: boric acid blend.
Interfacial properties of polymethyl α-cyanoacrylate and polybutyl α-cyanoacrylate
Authors: Florence A T , Haq M E , Johnson J R
Published: April 2011

Several physical properties of two polyalkyl α-cyanoacrylates relevant to their use in pharmaceutical dosage forms have been investigated. Formation of polymer films at several oil-water interfaces reveals films of diverse morphology. The retardation of solute transfer across an oil-water interface caused by the presence of polymer films formed in situ from the monomers has revealed that the methyl derivative forms the more effective barrier to the test solute, gentian violet. The emulsion-stabilizing properties of the methyl polymer have been studied, and the film-forming properties of the monomers spread from benzene onto water surfaces have been examined using a surface balance.
Methylmercury and the skeletal muscle receptor
Authors: von Burg R , Landry T
Published: April 2011

Methylmercury at a bath concentration of 2 × 10−5 m was capable of inhibiting muscular contractions of the isolated rat phrenic-nerve hemidiaphragm preparation. At the height of inhibition, nerve action potential could still be recorded and the muscles continued to respond to direct stimulation. The inhibition was not reversible with l-cysteine or d-penicillamine but limited protection was possible by prior treatment with (+)-tubocurarine. Treatment of frog rectus muscles with methylmercury (0·2 Mm for 15 min) resulted in a shift to the right of 1 log unit in the dose response curve to acetylcholine and a reduction in the maximum response of the tissue. The observed inhibitory action of methylmercury on neuromuscular transmission may be explained by an action on the disulphide bond believed to be present on a cholinergic receptor.
Anti-inflammatory actions of dapsone and its related biochemistry
Authors: Williams K , Capstick R B , Lewis D A , Best R
Published: April 2011

Dapsone has been examined by two established animal anti-inflammatory models and found to possess anti-inflammatory activity comparable with established non-steroidal anti-inflammatory drugs. Dapsone also possesses some biochemical properties common to other anti-inflammatory drugs.
Correlation of behavioural inhibition or excitation produced by bromocriptine with changes in brain catecholamine turnover
Authors: Snider Stuart R , Hutt Cheryl , Stein Bruce , Prasad A L N , Fahn Stanley
Published: April 2011

The dopamine agonist, bromocriptine, produced either inhibition or stimulation of motor behaviour in rats depending upon the dose and time after administration. Stimulation of motor activity occurred only with high doses after a 1–2 h delay. Both inhibition and stimulation were associated with decreased turnover of dopamine in the brain. Release of noradrenaline in brain and noradrenaline plus adrenaline in adrenal varied with motor activity. It is suggested that low doses of bromocriptine inhibit behaviour by activating an inhibitory presynaptic receptor, resulting in reduced synthesis and release of dopamine, whilst high doses cause behavioural excitation by activating the post-synaptic dopamine receptor.