bluuebunny/crossref_metadata_2025_split huggingface dataset:
The compaction properties of polyethylene glycols
Authors: Al-Angari A A , Kennerley J W , Newton J M 
Published: April 2011

Abstract
The mechanical properties of polyethylene glycol (PEG) powders of different average molecular weights have been characterized in terms of their yield pressure, determined from the densification of compacts by the method of Heckel. The yield pressure was found to be proportional to the molecular weight of the PEG. The densification which occurred during compaction was greater the lower the molecular weight. In terms of compact tensile strength, PEG 10000 produced the greatest strength for a given pressure. This arises from its ability to deform plastically to form a compact and be of sufficient intrinsic strength to resist fracture during the diametral compression test. Higher molecular weights PEGs do not allow sufficient plastic flow during consolidation for their inherent higher strength to be used.
Effect of protein on the absorption of phenytoin through everted gut preparations
Authors: Rosen A , Macheras P 
Published: April 2011

Abstract
The transfer of phenytoin across everted gut membrane has been measured both from solutions and from media where the drug is dissolving at different pH. Introduction of protein into the mucosal medium caused varying effects. Protein binding in the mucosal solution causes a decrease in the apparent transfer rate. However, in accord with previous findings, at pH 4 both the solubility and dissolution rate of phenytoin increase in the presence of protein, and this can lead to increased transfer rates. Effects such as these may account for the effect of food on phenytoin bioavailability.
Comparison of the effects of sodium salicylate, disodium ethylenediaminetetraacetic acid and polyoxyethylene−23−lauryl ether as adjuvants for the rectal absorption of sodium cefoxitin
Authors: Nishihata Toshiaki , Tomida Hisao , Frederick Gregory , Rytting J Howard , Higuchi Takeru 
Published: April 2011

Abstract
Sodium salicylate, disodium ethylenediaminetetraacetic acid (EDTA) and polyoxyethylene−23-lauryl ether (POE) significantly enhanced the absorption of cefoxitin from the rectum but with the following differences. (1) The effectiveness of salicylate or EDTA was enhanced by sodium chloride, whereas the activity of POE was not. (2) Although the ratios of plasma cefoxitin peak values to cefoxitin dose were constant with POE or EDTA, the peak to dose ratios with salicylate decreased with increasing cefoxitin concentration. (3) Phlorizin and 4, 4′-diisothiocyanostilbene−2, 2′-disulfonic acid (DIDS) inhibited the effectiveness of salicylate, but did not influence the adjuvant action of either POE or EDTA. (4) Although treatment with salicylate resulted in slightly less protein release than treatment with NaCl, both POE and EDTA increased the release of protein from the rectal mucosa. It appears that the effects of salicylate occur at the protein fraction of the rectal mucosa through a saturable process whereas the adjuvant action of POE and EDTA appears to involve some irreversible disruption of the membrane.
The inhibitory effects of ranitidine and Cimetidine on propranolol elimination by the rat isolated perfused liver
Authors: Jones D Brian , Ching Michael S , Morgan Denis J , Anderson Jeanette D , Smallwood Richard A 
Published: April 2011

Abstract
The effect of low (50 μg) and high (1 mg) doses of the histamine H2-receptor antagonists cimetidine and ranitidine on the first pass extraction of propranolol was studied in the rat isolated perfused liver. Both low and high dose cimetidine increased the area under the perfusate propranolol concentration time curve (AUC) 4 to 5−fold. Although low dose ranitidine did not alter propranolol AUC, high dose ranitidine increased it to the same extent as cimetidine. These results indicate that ranitidine has a clear propensity for microsomal inhibition, but one which is unlikely to be manifest at therapeutic dosage.
The effect of indoramin on plasma lipids in hypercholesterolemic patas monkeys
Authors: Pierce Vanessa , Shepperson Nicholas B , West-Watson Andrew 
Published: April 2011

Abstract
In patas monkeys fed a high cholesterol diet, chronic dosing with the antihypertensive agent indoramin increases the cholesterol ratio by raising the plasma HDL-C concentration. Epidemiological evidence suggests that increasing HDL-C reduces the incidence of coronary heart disease (CHD). If, therefore, indoramin is able to evoke these changes in man it may be expected to favourably influence the progress of CHD.
Chronic lithium prevents REM sleep deprivation-induced increased responsiveness to apomorphine
Authors: Rodrigues Francisco Das Chagas , Zwicker AsteróIde Paulo , Calil Helena Maria 
Published: April 2011

Abstract
REM sleep deprivation of rats induces an increased responsiveness to dopaminergic agonists. Chronic lithium (Li) has been reported to prevent the development of dopamine receptor supersensitivity induced by other agents. The effects of chronic dietary Li administration (producing a mean serum level of 0.96 mequiv. litre−1) and 96 h REM sleep deprivation were studied. Chronic Li completely blocked the increased stereotypy, and partially prevented the aggressive behaviour induced, respectively, by 0.6 and 5 mg kg−1 of apomorphine in REM sleep deprived rats compared with the appropriate control groups. This study constitutes the first attempt to evaluate chronic lithium effects on rats undergoing REM sleep deprivation, chosen as another method of inducing alteration of dopaminergic sensitivity.
Dissolution rate measurements of sparingly soluble compounds with the Coulter Counter model TAII
Authors: Nyström C , Mazur J , Barnett M I , Glazer M 
Published: April 2011

Abstract
A Coulter Counter, Model TAII was used to determine both solubility and dissolution rate from suspensions of griseofulvin and hydrocortisone acetate, where the initial particle size and shape had been characterized. The method assesses the weights and surface areas of particles remaining undissolved as a function of time. A comparison with a conventional method, assessing dissolved quantities of materials, showed that solubility data of the same order of magnitude can be obtained. The TAII data fitted a previously established equation that linearly relates log solubility and log of the intrinsic dissolution rate and indicated that the dissolution process was not diffusion controlled. The TAII method described is a rapid and convenient means of estimating the solubility and dissolution rate where no adequate technique for analysing the dissolved fraction exists.
The effect of nifedipine and verapamil on the pendular movements of the rabbit isolated ileum
Authors: Beleslin D B , Samardẑić Ranka , Terzić Branka , Jovanović-mićić Danica 
Published: April 2011

Abstract
The inhibitory effect of calcium antagonists such as nifedipine and verapamil on the pendular movements of the rabbit isolated ileum was investigated. Nifedipine and verapamil depressed or abolished the pendular movements. The inhibitory effects of nifedipine and verapamil were concentration-dependent. Nifedipine is about 1000 times more potent than verapamil. Calcium ions failed to reverse the inhibitory effects of nifedipine and verapamil. Calcium antagonists which influence the motor activity of the digestive tract, therefore, could have therapeutic use independent of their action on the cardiovascular system.
Comparison of the potency of 8−phenyltheophylline as an antagonist at A1 and A2 adenosine receptors in atria and aorta from the guinea-pig
Authors: Collis M G , Palmer D B , Saville V L 
Published: April 2011

Abstract
The potency of 8−phenyltheophylline as an antagonist at A, adenosine receptors in guinea-pig atria and at A2 adenosine receptors in the guinea-pig aorta has been investigated. 8-Phenyltheophylfine was an apparently competitive antagonist of the negative chronotropic effect of adenosine, 2-chloroadenosine, L- N6 -phenyl-isopropyl adenosine (L-PIA) and 5′- N-ethylcarboxamide adenosine (NECA) on atria and of the relaxant effect of adenosine, 2−chloroadenosine and NECA on the aorta. The pA2 values for 8−phenyltheophylline ranged from 6.4 to 6.6 and were not significantly different, irrespective of the agonist or tissue used. These results indicate that 8−phenyltheophylline is a relatively potent antagonist at adenosine receptors but does not exhibit selectivity for either of the putative sub-types in isolated tissues.
The metabolic chiral inversion of 2−arylpropionic acids–-A novel route with pharmacological consequences–-a correction
Authors: Hutt Andrew J , Caldwell John 
Published: April 2011

Abstract
In our recent review (Hutt & Caldwell 1983) on the metabolic chiral inversion of the 2−aryl propionic acids, Fig. 1 presented flying wedge diagrams to depict the three-dimensional structures of the enantiomers, assigned according to Shen (1979). Close examination of the Figure, in the light of model building, reveals that the absolute configurational designation of these structures is incorrect and should be reversed, i.e. the enantiomer labelled by us as R(-) is in fact S(+) and vice versa. We apologise for this error, and would also point out that the diagram of Shen (1979) upon which our assignments were based is similarly incorrect.
Effects of composition, moisture and stearic acid on the plasto-elasticity and tableting of paracetamol-microcrystalline cellulose mixtures
Authors: Bangudu A B , Pilpel N 
Published: April 2011

Abstract
Measurements were made under various conditions of the stress relaxation (SR) and elastic recovery (ER) of mixtures of paracetamol and microcrystalline cellulose (Avicel) and of the tensile strengths (T) of their tablets. T was inversely proportional to ER/SR. Tablets laminated or capped when they contained less than 25% w/w of cellulose and the value of ER/SR measured at 20 kN over a compression/decompression/ejection cycle of 2 min, was greater than 9. Addition of between 2 and 4% w/w of water increased the tensile strengths of tablets, provided they contained less than 75% w/w of cellulose, but more water caused decreases in T. Additions of up to 10% w/w stearic acid also caused decreases in T. Explanations are provided for the results.
Intranasal drug delivery by spray and drops
Authors: Hardy J G , Lee S W , Wilson C G 
Published: April 2011

Abstract
A solution of 99m Tc-labelled human serum albumin was administered into the nose as a spray and as one or three drops. The patterns of deposition and the rates of clearance in normal subjects were monitored by gamma scintigraphy. The spray was deposited mainly in the atrium, and cleared slowly into the pharynx. The single drop spread more extensively than the spray, while the three drops were sufficient to cover most of the walls of the nasal cavity. Clearance was faster following administration of the drops. These factors have implications when designing dosage regimens for drugs administered by the intranasal route.
Prazosin binding to human α1-acid glycoprotein (orosomucoid), human serum albumin, and human serum. Further characterization of the 'single drug binding site' of orosomucoid
Authors: Brunner F , Müller W E 
Published: April 2011

Abstract
The plasma protein binding of the α1-adrenergic blocking agent prazosin was investigated by means of circular dichroism (CD) and equilibrium dialysis (ED) measurements. The interaction of prazosin with human α1-acid glycoprotein (α1-AGP) results in pronounced negative extrinsic Cotton effects at 255 nm and a smaller negative band at 285 nm which are associated with the binding of prazosin to only one site of the protein. Various basic drugs, and warfarin also, at 50μM displace prazosin 10 μM from its binding site on α1-AGP and reduce the CD-spectra at 255 nm by 26% (disopyramide), 52% (mepivacaine), about 70% (verapamil, biperiden), and 90–100% (trihexyphenidyl, warfarin). (±)-Propranolol reduces the CD-spectra by 76%, its (-)-isomer by 89%, and the (+)-isomer by 65%. ED experiments indicated that the binding of prazosin to α1-AGP is saturable with an association constant of 48 000 M−1 and 0.85 binding sites per protein molecule. Displacement of prazosin from α1-AGP by the same drug as used for the CD experiments at displacer/porazosin ratios of 5 resulted in comparable reductions of the fraction bound as obtained by the CD experiments. Prazosin was also highly bound to human serum albumin (600 μM) with about 80–85% bound at prazosin concentrations from 1–100 μM. Since prazosin binding to human serum is only slightly higher (80–90%) it is concluded that prazosin binding in serum is largely mediated by the albumin fraction. The results indicate that prazosin binds to the single drug binding site of human α1-AGP, that this site is slightly stereospecific for propranolol, and that anionic as well as cationic drugs bind with high affinity to this drug binding site of α1-AGP.
A possible pH-controlled drug delivery system based on a derivative of the polysaccharide scleroglucan
Authors: Alhaique F , Riccieri F M , Santucci E , Crescenzi V , Gamini A 
Published: April 2011

Abstract
Four carboxylated derivatives of scleroglucan have been obtained by oxidation, to different extents, of the glucopyranose side chains of the natural polysaccharide. The diffusion of model molecules through aqueous solutions of these new products was measured at various pH values. The reversible pH induced sol-gel transition of some of the polyelectrolyte solutions tested effects a remarkable variation in the diffusion rate of the permeating species; in this sense the most interesting polysaccharide appears to be the product with 70% oxidized glucopyranose moieties. The behaviour of scleroglucan and its derivatives has been compared with that of carboxymethylcellulose and the mechanism involved in drug permeation and release discussed. The possible application of one of the new products in controlled release formulations for oral use is also reported.
In-vitro and in-vivo metabolism of the presynaptic dopamine agonist 3-PPP to a catecholic analogue in rats
Authors: Rollema Hans , Mastebroek Dora , Wikströum Håkan , Horn Alan S 
Published: April 2011

Abstract
The dopamine agonist 3-PPP and its enantiomers are hydroxylated in-vitro by rat liver microsomes to the catecholamine 3-(3,4-dihydroxyphenyl)- N-n-propylpiperidine (4-OH-3-PPP) with Km and Vmax values of about 1 μM and 2 nmol (mg protein)−1 min−1 respectively. As the catecholamine formed appears to be a good substrate for catechol- O-methyltransferase, in-vivo catecholamine formation in rats from 3-PPP was only detectable after inhibition of COMT by tropolone. The resulting brain levels of 4-OH-3-PPP, as measured by HPLC with electrochemical detection 45 min after administration, were about 350 pmol g−1 after i.p., and about 100 pmol g−1 after s.c. injection of 45 μmol kg−1 3-PPP, with no significant difference between racemic, (+) or (-) 3-PPP. It was estimated that these catecholamine levels represent about 1–5% or the 3-PPP levels after i.p., and about 0.2-0.5% after s.c. administration of 3-PPP. The relevance of this metabolic conversion of 3-PPP for its pharmacological profile is discussed.
Cholic acids/salts as barriers to diffusing species: effect of pH
Authors: Alhaique F , Memoli A , Santucci E 
Published: April 2011

Abstract
Bile acids have been absorbed on a microporous polypropylene membrane and the diffusion of ionic and non-ionic compounds through the barriers obtained has been studied at different pH values. Results indicate that permeation rates are affected by environmental pH conditions and an explanation of this behaviour is proposed. This study represents an approach for a pH-controlled drug delivery system.
Distribution of azapropazone and its principal 8-hydroxy-metabolite in plasma, urine and gastrointestinal mucosa determined by HPLC
Authors: Rainsford K D 
Published: April 2011

Abstract
Methods are described for the HPLC determination of azapropazone and its 8-hydroxyl metabolite in plasma, urine and gastrointestinal mucosae after purification of samples on reverse-phase mini columns. Plasma levels of the drug in gouty patients receiving 900–2400 mg daily were relatively constant after 5 days, though overall the values were higher than after a single dose. Gastric absorption of azapropazone in rats is relatively rapid suggesting that the low gastric irritancy is probably due to its weak inhibitory effects on prostaglandin and mucus synthesis rather than slow gastric absorption.
GABA inhibits excitatory neurotransmission in rat pelvic ganglia
Authors: Maggi Carlo Alberto , Santicioli Paolo , Meli Alberto 
Published: April 2011

Abstract
Intravenous GABA inhibited, in a bicuculline-sensitive manner, contractions of the urinary bladder induced by preganglionic nerve stimulation in urethane anaesthetized rats, while it had no significant effect on contractions produced by postganglionic nerve stimulation. In addition, intravenous GABA strongly inhibited DMPP-induced bladder contractions; this effect was also prevented by bicuculline. These experiments suggest that GABA inhibits excitatory neurotransmission in rat pelvic ganglia through a mechanism involving, at least in part, the activation of postsynaptic GABA A receptors.
Repeated treatment with imipramine or amitriptyline increases the locomotor response of rats to (+)-amphetamine given into the nucleus accumbens
Authors: Maj J , Wedzony K 
Published: April 2011

Abstract
Effects of bilateral injections of (+)-amphetamine (5 μg/0.5 μl) into the nucleus accumbens were investigated in rats treated repeatedly with imipramine or amitriptyline. Repeated but not acute administration of either drug enhanced the locomotor hyperactivity induced by (+)-amphetamine given 2 or 72 h after the last dose of antidepressant. The results indicate that the increased responsiveness of the mesolimbic dopaminergic system may be involved in the action of antidepressant drugs.
Highly potent inhibition of prostaglandin 15-hydroxydehydrogenase in-vitro and of prostaglandin inactivation in perfused lung by the new azobenzene analogue, Ph CL 28A
Authors: Berry C N , Hoult J R S , Phillips J A , Mccarthy T M , Agback H 
Published: April 2011

Abstract
The new azobenzene analogue Ph CL 28A (2-hydroxy-5-(3,5-dimethoxycarbonyl-benzoyl)-benzene acetic acid) potently inhibited prostaglandin 15-hydroxydehydrogenase (PGDH) in the nanomolar range in-vitro and inhibited prostaglandin inactivation in rat perfused lung at similar concentrations, and is the most potent PGDH inhibitor yet available. It was synthesized because electronegative substituents in the B ring of homosalazine enhance PGDH inhibitory potency. Ph CL 28A inhibited human placental PGDH non-competitively with regard both to substrate PGF2α (Ki = 18.7 ± 0.9 nM) and the NAD+ cofactor (Ki= 57.6 ± 2.9 nM); inhibition was greatly reduced at pH &gt; 8.0. PhCL 28A hydrolyses spontaneously in alkali (t 1/2 at pH 9.0 = 45 h) to the less active dicarboxylic acid (IC50 human placental PGDH 1.6 μM versus 0.028 μm for Ph CL 28A). The new analogue is 1000 x more active than the parent compound sulphasalazine from which it derives. The IC50 values for five azobenzene analogues in rat perfused lung (Ph CL 28A = 72 nM) correlated strongly with those obtained using purified PGDH (r = 0.99), suggesting that they inhibit pulmonary prostaglandin degradation at the enzyme step rather than at the hypothetical carrier. The new compound will be a useful probe for PGDH structure and function.
The binding of flurbiprofen to plasma proteins
Authors: Aarons Leon , Khan Azhar Z , Grennan David M , Alam-Siddiqi Masooma 
Published: April 2011

Abstract
The binding of flurbiprofen to human serum albumin and normal plasma was measured using ultracentrifugation. Flurbiprofen was bound in excess of 99% in all cases. Over the concentration range normally associated with therapy the data could be adequately described by a one-site binding model. The association constant decreased with increasing protein concentration, being 3.04 times 106 M− 1 at an albumin concentration of 2 g/100 ml and 1.19 times 106 M− 1 at a concentration of 4 g/100 ml. Flurbiprofen binding showed no dependence on pH over the range 7.0 to 8.0.
β-Kainic acid is not an amino acid antagonist
Authors: Stone Trevor W , Collins J F 
Published: April 2011

Abstract
β-Kainic acid has been reported to have anticonvulsant properties. In view of its structural relationship to α-kainic acid it has therefore been tested for antagonist activity at excitatory receptors for N-methylaspartate, quisqualate and α-kainate using anaesthetized rats and brain slice preparations. No antagonism was found against these three agonists though β-kainate itself caused excitation. If β-kainate interferes with excitatory amino acid neurotransmission it probably acts presynaptically.
Investigation of the film formation of magnesium stearate by applying a flow-through dissolution technique
Authors: Johansson Mats E , Nicklasson Martin 
Published: April 2011

Abstract
The film formation of magnesium stearate on the surface of acetylsalicylic acid was investigated by applying a flow-through dissolution technique. The effect of mixing time, lubricant surface area, and the addition of colloidal silica was studied. The film formation increased by increasing mixing time. The final level reached was independent of the specific surface area of the lubricants, but granular magnesium stearate gave a lower surface coverage than the powdered lubricants. The lubricating effect was independent of the mixing time and specific surface area of the lubricants. Colloidal silica was found to interact primarily with the free fraction of magnesium stearate.
9β-Methylcarbacyclin, a stable prostacyclin analogue, in prevention of platelet losses during charcoal haemoperfusion
Authors: Hughes R D , Lanoley P G , Guarner F , Williams Roger 
Published: April 2011

Abstract
The effect of 9β-methylcarbacyclin, a stable analogue of prostacyclin, as a platelet protective agent, has been investigated during in-vitro charcoal haemoperfusion with fresh heparinized human blood, a model of progressive platelet damage. There were no platelet losses over 3 h perfusion after an initial bolus (1 μg ml−1) of 9β-methylcarbacyclin (101.6 ± s.e. 1.9% of initial value) whereas in the paired control circuit there was a significant reduction in the platelet level (73.5 ± 4.1%, P &lt; 1.05). Prevention of rises in plasma thromboxane B2 by 9β-methylcarbacyclin confirmed the lack of platelet damage and a significant, but less marked, effect on white cell losses was observed. In a second series of experiments a bolus of 9β-methylcarbacyclin in one circuit was compared with prostacyclin infusion in the other which demonstrated that this prostaglandin analogue was as effective as prostacyclin and on the basis of these initial results it would merit clinical evaluation.
α-Tocopherol as agonist in hypoxia
Authors: Kelly M J 
Published: April 2011

Abstract
In hypoxia, but not normoxia, α-tocopherol (vitamin E) acts as an agonist in guinea-pig isolated colon, producing dose-dependent increases in contractile activity. This effect is mimicked by agents, vitamin K1 and phytol, which contain a structural similarity to the phytyl side chain of α-tocopherol, but is antagonized by vitamin K3 which has a structure similar to the chromane ring of vitamin E. All of the agonist responses were blocked by atropine and potentiated by physostigmine but were unaffected by nexamethonium. However, responses to acetylcholine were not antagonized by vitamin K3 and these data suggest that α-tocopherol, phytol, vitamins K1 and K3 may be acting on a ‘hypoxia receptor’ which mediates release of acetylcholine onto muscarinic receptors.