bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypertension: its effect on the stimulated release of dopamine-β-hydroxylase in the rat
Authors: Algate D R , Leach G D H 
Published: April 2011

Abstract
Plasma dopamine- β-hydroxylase (DBH) concentrations have been postulated as providing an index of sympathetic nerve activity. Using a microspectrophotometric assay system, plasma DBH concentrations have been measured in emergent blood from autoperfused heart, spleen and mesentery of normotensive, deoxycorticosterone (doca)/NaCl-treated, Goldblatt (1 kidney) renal and spontaneously hypertensive rats following sympathetic nerve outflow stimulation. Changes in plasma DBH concentrations as a result of sympathetic nerve outflow stimulation rates of 1–25 Hz for the mesentery and spleen and 1–4 Hz for the heart, were found to be frequency-dependent in all groups. Significantly greater amounts of DBH were found in the perfusate from the spleen (1–25 Hz) and mesentery (3–25 Hz) but not the heart (0·5–4 Hz) of renal hypertensive rats compared with normotensive controls. Significantly greater concentrations of DBH were released from the spleen but not the mesentery in all hypertensive groups following high stimulation frequencies of 12 and 25 Hz. It is concluded that there is a relation between plasma DBH concentrations and sympathetic nerve activity. Furthermore, greater amounts of the enzyme are released from the spleen and mesentery of chronic renal hypertensive rats following sympathetic nerve stimulation.
Comparative study of the dopamine-sensitive adenylate cyclase in the striatum and hypothalamus of rat brain
Authors: Roufogalis B D , Thornton M , Wade D N 
Published: April 2011

Abstract
Stimulation by dopamine of adenylate cyclase in homogenates of rat brain striatum was enhanced in the presence of ATP (0.6-3 mm) and GTP (10–100μM). The stimulation by dopamine appeared to be the result of its antagonism of inhibition of adenylate cyclase by GTP or higher concentrations of ATP. Stimulation of the enzyme by dopamine was also dependent on MgCl2, and was maximal at MgCl2 concentrations of at least two fold excess over ATP. While ATP did not inhibit the adenylate cyclase in homogenates of the ventral hypothalamus, GTP (10–100 μM) significantly stimulated it. Dopamine stimulated the adenylate cyclase in the hypothalamus. This action was blocked by chlorpromazine (10 μM) and phentolamine (100 μM) but not by an analogue of chlorpromazine having no neuroleptic activity or by propranolol (100 μM).
Percutaneous absorption: interfacial transfer kinetics
Authors: Albery W John , Hadgraft Jonathan 
Published: April 2011

Abstract
A new rotating diffusion cell is described in which a solute diffuses through a rotating filter. The transport of the solute to both sides of the filter is controlled by the rotation. The filter is filled with an organic phase. The rate of transfer of the solute through the filter is determined by the transport and by the kinetics of the interfacial transfer reactions. Since the transport is controlled the rate constant for the transfer reaction can be measured. Results for eleven different systems are reported and it is found that the rate constants are all smaller than 10−4 ms−1.
The mechanical strength of film-coated tablets
Authors: Fell J T , Rowe R C , Newton J M 
Published: April 2011

Abstract
The mechanical strength of film-coated tablets has been assessed using the diametral compression test. The results show that the influence of the film is more complex than that suggested by Stern (1976). The film may increase the breaking load of the core itself by acting as a padding material during the test and also by filling in surface irregularities. The film may also have enough intrinsic strength and elasticity to hold the core together once it has broken. The maximum breaking load to completely fracture the coated tablet is related to film properties, but the relation is not a simple one.
Improved gas-chromatographic method and micro-extraction technique for the measurement of nicotine in biological fluids
Authors: Feyerabend C , Russell M A H 
Published: April 2011

Abstract
A rapid and sensitive method for the measurement of nicotine in plasma, urine, saliva and breast milk is described. An internal standard (quinoline) is added to the samples and these are made alkaline and extracted with diethyl ether. The solvent is evaporated to small bulk and extracted with dilute acid which is then made alkaline. The nicotine is finally extracted into butyl acetate and an aliquot of this extract is injected onto a gas-chromatograph fitted with a nitrogen detector. Quantitation relies on comparison of peak areas and the calibration curve is linear over the concentration range 0.5 to 100 ngml−1. Nicotine concentrations as low as 0.1 ng ml−1 can be measured. In addition, a micro-method is described which requires only 100 μl of sample and yields an accurate result in 5 min.
A spectropolarimetric assay of (−)-adrenaline in compendial formulations
Authors: Davidson A G 
Published: April 2011

Abstract
A method is described for the determination of (−)-adrenaline in certain formulations containing adrenaline hydrogen tartrate at concentrations down to 0.18 mg ml−1 (1:10000 adrenaline). The assay is based upon a spectropolarimetric measurement at 249 nm of sample solutions, suitably treated to remove interfering substances. The rotation of the sample solutions is corrected for the rotation of the tartaric acid species which is determined by a difference rotation measurement on equimolar sample solutions at pH 1.1 and pH 5.6. The concentration of (−)-adrenaline in the sample is calculated from the net rotation at 249 nm due to the (−)-adrenaline and the total concentration of adrenaline ((+)- and (−)-isomers) determined by a published spectrofiuorimetric method. The assay is specific for (−)-adrenaline in the presence of (+)-adrenaline, (+)-tartaric acid, adrenaline sulphonic acid and low levels of adrenochrome.
Effects of drugs on the formation of 3-methoxytyramine, a dopamine metabolite, in the substantia nigra, striatum, nucleus accumbens and tuberculum olfactorium of the rat
Authors: Westerink Ben H C 
Published: April 2011

Abstract
3-Methoxytyramine (3-MT) was assayed with a sensitive and rapid liquid chromatographic separation on a Sephadex G 10 column in combination with a fluorimetric detection in a continuous flow system. The method made it possible to measure pargyline-induced 3-MT concentrations in various regions of a single rat brain. After haloperidol, morphine or sulpiride treatment, pargyline-induced 3-MT concentrations in the striatum, nucleus accumbens, tuberculum olfactorium and substantia nigra of the rat were comparable with reported changes of homovanillic acid concentrations. Dose-response curves for 3-MT increase in various brain regions after (+)-amphetamine pretreatment were studied. The effect of (+)-amphetamine on 3-MT formation was much more pronounced in nerve terminal areas, especially in the mesolimbic structures. The influence of apomorphine, γ-hydroxybutyric acid, haloperidol, reserpine or combined treatment of haloperidol and (+)-amphetamine revealed pronounced differences on regional 3-MT concentrations, indicating important differences between the regulation of dopamine metabolism in the substantia nigra and nerve terminal areas.
Comparative evaluation of six techniques for determining the Michaelis-Menten parameters relating phenytoin dose and steady-state serum concentrations
Authors: Mullen P W , Foster R W 
Published: April 2011

Abstract
Using randomly generated data within set error limits, the Michaelis-Menten parameters Dmax and Km relating steady-state serum phenytoin concentrations (Css) and dose (D) were determined by 5 graphical techniques and an iterative computer fit to the hyperbolic equation. The best mean estimates of Dmax and Km were provided by the latter. Assuming the experimental error to be in Css the results indicate that the most reliable graphical technique is that based on the equation CSS = Dmax -CSS/D - Km. However, considering its obvious simplicity and relative reliability the direct linear plot is recommended for clinical use.
Effect of paracetamol on amylobarbitone hydroxylation in man: a gas chromatographic method for simultaneous estimation of underivatized paracetamol and barbiturates
Authors: Kinsella Helen C , Smith Susan , Rogers H J , Toseland P A 
Published: April 2011

Abstract
A rapid and specific technique for the simultaneous gas chromatographic estimation of underivatized paracetamol and barbiturates using an alkali flame ionization detector is described which is suitable for both forensic and pharmacokinetic investigations. An improved method for estimation of 3-hydroxyamylobarbitone is also detailed. These techniques were used in an investigation of the effects of oral administration of 1 g paracetamol 8 hourly on the formation of 3-hydroxyamylobarbitone from a single oral dose of 200 mg sodium amylobarbitone. No significant changes were found in the plasma concentrations and total body clearance of amylobarbitone nor was there any alteration in the urinary elimination of 3-hydroxyamylobarbitone.
The gastrointestinal absorption of paracetamol in the rat
Authors: Bagnall W E , Kelleher J , Walker B E , Losowsky M S 
Published: April 2011

Abstract
The absorption of [3H]paracetamol by rat small intestine, colon and stomach was studied in vivo and in vitro. Small intestinal in vivo studies, using a wide range of drug concentrations, showed that absorption was efficient and uniform throughout the small bowel, no site showing preferential absorption. Double reciprocal and direct plots indicated first order kinetics. The pattern was not observed when uptake was occurring from high concentrations of paracetamol in suspension. Gastric and colonic in vivo studies showed that there was appreciable absorption of [3H]paracetamol from these sites. In vitro studies using everted intestinal sacs showed no effect on paracetamol transfer when the incubation temperature was lowered to 10 °C or when iodoacetate (5 times 10−2m) and 2.4 dinitrophenol (5 times 10−4m) was added to the incubation medium. There was, however, a significant reduction in transfer of paracetamol against a concentration gradient of 10:1 applied across the mucosa. These data suggest that the uptake of paracetamol is by a passive transport process and confirm the efficiency of paracetamol absorption observed indirectly by others.
Additivity of action between polysorbate 80 and polymyxin B towards spheroplasts of Pseudomonas aeruginosa NCTC 6750
Authors: Brown M R W , Geaton E M , Gilbert P 
Published: April 2011

Abstract
When polymyxin B and polysorbate 80 were used together against spheroplasts of Pseudomonas aeruginosa, the activities were found to be additive. These substances have previously been reported to act synergistically against P. aeruginosa, but little or no intrinsic activity towards intact cells has been attributed to polysorbate 80. We suggest that in addition to enhancing polymyxin B penetration to the cytoplasmic membrane, polysorbate 80 may also act as an antimicrobial agent when polymyxin-induced damage to the outer membrane facilitates the surfactant's passage through the cell envelope.
The granulation of ternary mixtures containing lactose and boric acid with different starches
Authors: Jaiyeoba K T , Spring M S 
Published: April 2011

Abstract
Ternary mixtures of lactose, boric acid and starch have been granulated by massing and screening. The properties of the granules have been compared with those resulting from granulation of blends of lactose and boric acid without starch. Potato, maize and rice starches have been studied as the third component at concentrations similar to those employed in tablet formulations. The starches caused a reduction in both mean granule size and granule strength. The effect is dependent on the proportions of the excipients. Increasing the amount of binder solution used gave bigger, stronger granules but did not compensate for the effects produced by the starches.
Sustained release of a dual antimalarial system
Authors: Wise Donald L , Gresser Joseph D , McCormick Gerald J 
Published: April 2011

Abstract
The sustained release of a dual drug system in a biodegradable carrier was evaluated in rhesus monkeys and mice. The two drugs were sulphadiazine (WR-7557) (3H-labelled) and 2,4-diamino-6-(2-naphthylsulphonyl)quinazoIine (WR-158122) (14C-Iabelled). The carrier was a polymer of L-lactide (90 parts by weight) and glycolide (10 parts), with a molecular weight of 46 000. The dual system injected was a blend of two preparations, each 50% (w/w) of the appropriate drug in the polymer, in a weight ratio of ten parts of the sulphadiazine system to one part of the WR-158122 system. This blend, as cryogenically ground particles, was injected intramuscularly into three monkeys; a fourth monkey received an equivalent dose of a 10:1 mixture of the pure drugs. Excretion of radioactivity in urine and faeces was measured over 13 weeks. Similar studies were done with mice. In monkeys, 14C-labelled material derived from WR-158122 was excreted at a nearly uniform rate; expressed as WR-158122, the rate of excretion from the pure drug mix was approximately 50 μg day−1 from week three to week 13, while the drug/polymer matrix released the drug at approximately 26 μg day−1 during this period. Recovery of tritiated materials derived from sulphadiazine was approximately 82% of the injected dose in the first three weeks and only a slight difference in release characteristics of the pure drug mix and the mixed drug/polymer matrices was observed. Results of studies with both mice and monkeys were generally consistent.
Characterization of receptors on postganglionic cholinergic neurons in the guinea-pig isolated ileum
Authors: Ennis Christine , Janssen P A J , Schnieden H , Cox B 
Published: April 2011

Abstract
Dopamine, apomorphine, noradrenaline and isoprenaline reduced the response of the isolated guinea-pig ileum to exogenous acetylcholine by a maximum of 40%. Propranolol reversed this inhibition whilst phentolamine and pimozide were ineffective, suggesting that the drugs were acting on a post-synaptic β-adrenoceptor. The same agonists were more effective as inhibitors of the response to transmural electrical stimulation of the ileum, lower doses producing almost complete inhibition. This inhibition was partially antagonized by phentolamine, pimozide and propranolol. Clonidine proved to be the most potent inhibitor of the response to transmural electrical stimulation, whilst phenylephrine was ineffective. pA2 determinations showed that phentolamine was a potent antagonist of clonidine but a weak antagonist of apomorphine whilst for pimozide the opposite was true. The results suggest that there are two populations of prejunctional receptors on the cholinergic nerves innervating the smooth muscle of the guinea-pig ileum. One receptor is similar to a classical prejunctional α-adrenoceptor and the other resembles a central dopamine receptor.
The non-specific membrane binding properties of ΔA9-tetrahydrocannabinol and the effects of various solubilizers
Authors: Roth Sheldon H , Williams Peter J 
Published: April 2011

Abstract
The binding of [3H]δ9-tetrahydrocannabinol to crude and purified synaptosomal membrane suspended in either Krebs solution or 10mM sodium phosphate buffer was examined. The membrane/buffer partition coefficient was found to be 12 500, and was constant over a free concentration range of 10−8 to 10−6m. Binding was similar in both suspending media, and to both crude and purified synaptosomal membrane. The solubilizing agent Cremophor E.L. (8 μg ml−1) decreased the partition coefficient by one-half, and by greater than 99 % at 0.4 mg ml−1. Similar effects were observed with Tween 80, while ethanol caused a maximum decrease of 60%. Membrane concentrations of THC were calculated at various effective concentrations reported in the literature, and were within the range predicted by the Meyer-Overton rule of anaesthesia. An apparent non-specific interaction with neuronal membranes and effective membrane concentrations of the order 2 times 10−1 to 1 times 10−2 mol kg−1 suggests THC may exert some of its effects by a mechanism analogous to the general anaesthetics, and thus may be classified as a partial anaesthetic.
Acidic metabolites of Δ1-tetrahydrocannabinol isolated from rabbit urine
Authors: Nordqvist Marianne , Lindgren Jan-Erik , Agurell Stig 
Published: April 2011

Abstract
The in vivo metabolism of Δ1-tetrahydrocannabinol (Δ1-THC) was investigated in the rabbit after i.v. administration. Thirteen acidic metabolites were isolated from rabbit urine and identified by gas chromatography-mass spectrometry and by proton magnetic resonance spectroscopy. One additional metabolite was tentatively identified. All but three were new metabolites and all but one were oxidized in the pentyl side chain. The metabolites included dicarboxylic acids, monocarboxylic acids and mono- or dihydroxylated derivatives thereof. However, the dicarboxylic acid metabolites were the most prominent.
Plasticization of cellulose ethers used in the film coating of tablets
Authors: Entwistle C A , Rowe R C 
Published: April 2011

Abstract
Plasticizer/polymer interactions have been studied by measuring the intrinsic viscosities of both ethyl cellulose and hydroxypropyl methylcellulose in a series of dialkyl phthalates and in a series of liquid glycols respectively. A correlation was found between the intrinsic viscosity of the polymer/plasticizer solutions and the tensile strength, elongation at rupture and work done in stressing to failure of cast films—the mechanical properties being at a minimum when the intrinsic viscosity was at a maximum. This correlation held only within a homologous series of plasticizers and none was found for plasticizers of different structures. A relationship was found between the lowering of a calculated glass transition temperature of hydroxypropyl methylcellulose in the presence of the plasticizers propylene glycol, polyethylene glycol 200 and glycerol and the intrinsic viscosity of the corresponding solutions—the higher the viscosity the greater the lowering of the transition temperature.
Relative effects of different surfactants on intestinal absorption and the release of proteins and phospholipids from the tissue
Authors: Whitmore D A , Brookes L G , Wheeler K P 
Published: April 2011

Abstract
The actions of anionic, cationic and non-ionic surfactants on the absorptive capability of rat jejunal tissue in vivo were compared with their effects on the amounts of protein and phospholipid released from the mucosal surface under the same conditions. Release of a comparatively small amount of protein was accompanied by large increases in the absorption rates of both L-valine and salicylate, whereas much larger quantities of phospholipid were released before any increase in absorption was observed. Much of the released material appeared to be derived from mucus which was partly degraded after exposure to the higher concentrations of surfactants. The liberation of cholesterol by high concentrations of anionic surfactants suggested that some disruption of the mucosal membrane occurred under those conditions. The relative potency of the surfactants in stimulating both absorption of the solutes and the release of polypeptides and lipids followed the order: anionic &gt; non-ionic &gt; cationic. The possible pharmaceutical relevance of these findings is discussed.
Corticosterone - an anxiogenic or an anxiolytic agent?
Authors: File Sandra E , Vellucci Sandra V , Wendlandt Sabine 
Published: April 2011

Abstract
Corticosterone (3–12 mg kg−1, i.p., giving rise to plasma corticosterone concentrations from 26.7 to 89.0 μg/100 ml) failed to have a significant anxiogenic action. Instead, corticosterone (3 mg kg−1) had a significant anxiolytic effect in the social interaction test of anxiety.
Adrenalectomized rats had very low levels of social interaction; but adrenalectomized rats that had been given replacement corticosterone therapy did not differ from the shamoperated controls. Thus, corticosterone appears to have the opposite effect to that previously reported for ACTH. Possible mechanisms for the observed results are discussed.
Muscimol and related GABA receptor agonists: the potency of GABAergic drugs in vivo determined after intranigral injection
Authors: Arnt J , Scheel-Krüger J , Magelund G , Krogsgaard-Larsen P 
Published: April 2011

Abstract
Contralateral turning behaviour following unilateral intranigral injection of a large series of GABA analogues was investigated. The results indicated that the turning behaviour was induced stereospecifically and was selectively antagonized by the GABA antagonist bicuculline methochloride. The comparative potencies of a series of GABA agonists related to muscimol in general corresponded well to the affinity for 3H-GABA receptor sites and to the depressant action on single neurons using microelectrophoretic administration. However, the GABA agonists trans-aminocrotonic acid and 3-aminopropanesulphonic acid were much weaker than expected from in vitro studies. The GABA-uptake inhibitors nipecotic acid and guvacine showed only weak and short-lasting effects. The GABA-transaminase inhibitor γ-acetylenic GABA showed delayed effects compared with the agonists which acted immediately. It is proposed that this behavioural effect may be a sensitive and quantitative method for evaluation of GABA agonists in vivo.
Hypothermic effects of apomorphine homologues in mice
Authors: Menon M K , Clark W G , Cannon J G 
Published: April 2011

Abstract
A single intraperitoneal (i.p.) injection in mice of apomorphine (I) and its analogues norapomorphine (II), N-ethylnorapomorphine (III), N-n-propylnorapomorphine (IV) and apocodeine (V), caused dose-related decreases in deep-core body temperature. The neuroleptic agent haloperidol blocked the hypothermia produced by these apomorphines but α-methyl-p-tyrosine failed to do so. This indicated a direct post-synaptic stimulation of dopamine receptors. Methysergide potentiated the hypothermic effect of the apomorphine analogues. Taking the amount of apomorphine to produce a 3 °C fall in temperature at 30 min as unity, the approximate relative potencies were: I 1.00, II 0.06, III 47.50, IV 85.00, V 0.340. The doses of the apomorphines needed to produce hypothermia were much less than those needed to cause stereotypy. The ratios of the minimal doses required to produce hypothermia, to those producing stereotypy were: I 8.82, II 4.00, III 125.00, IV 28.50, V 1.43.
The surface activity and self-association of some β-adrenoceptor blocking agents in aqueous solution
Authors: Attwood D , Agarwal S P 
Published: April 2011

Abstract
The surface activity at the air-solution interface of a series of β-adrenoceptor blocking agents has been determined. The drugs investigated included, propranolol, sotalol, oxprenolol, labetolol, timolol, metoprolol and acebutolol. Correlation between surface activity and local anaesthetic potency of the drugs is examined. Light scattering measurements have indicated self-association of sotalol, oxprenolol, acebutolol and metoprolol in 0.5 mol kg−1 sodium chloride. Critical micelle concentrations and aggregation numbers are reported.