bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bile-acid content of a commercial secretin
Authors: Kyffin D , Mclean I , Rutishauser S C B 
Published: April 2011

Abstract
Secretin, produced by the Boots Co., is an adsorbate on ox and pig bile acids of secretin from pig duodenum prepared after the method of Crick et al (1950). It is to be expected that this product will not only stimulate the secretion of fluid and electrolytes by the pancreas and the liver but that it will also increase the secretion of bile acids in bile. A recent study in rats showed that the infusion of secretin (Boots) did indeed increase biliary bile acid secretion but implied that this might be due to unidentified contaminants other than bile acids, in that the bile acid content of the batch of secretin used was found to be negligible (Romanski & Bochenek 1983).
Assessment of the wettability and surface energy of a pharmaceutical powder by liquid penetration
Authors: Buckton G , Newton J M 
Published: April 2011

Abstract
The use of a technique involving the assessment of the rate of penetration of a liquid into powder beds has been critically evaluated as a method for characterizing the wetting and surface energy of a hydrophobic powder (amylobarbitone). The choice of the perfect wetting liquid has been assessed, and the possible use and value of extrapolation techniques to indicate the theoretical result for water have been explored. Values of 99.5 and 102.8 obtained for the contact angle, and 25.7 and 26.9 mNm−1 for the critical surface energy, were the best estimates obtainable by this technique. Previously reported limitations of the Washburn equation have been considered.
In-vitro enhancement of cholesterol dissolution by commonly used drugs
Authors: King R O , Bell G D , Short A H , Heathcote B V , Hawkey C J 
Published: April 2011

Abstract
A rotating disc apparatus was used to study the dissolution of cholesterol in sodium cholate solutions and ox bile. Drugs with structures that render them capable of lowering interfacial resistance were tested and shown to increase cholesterol dissolution rates in both systems. In sodium cholate solutions, loperamide (3 times 10−4 M) increased the rate of dissolution by over six times, and a similar effect was observed with amitriptyline (3 times 10−3 M), diphenhydramine (3 times 10−3 M), dicyclomine (3 times 10−3 M) and propantheline (3 times 10−3 M). These drugs are as effective as benzalkonium chloride at these concentrations. Amitriptyline, propantheline, dicyclomine and diphenhydramine also increased cholesterol dissolution rates into ox bile. If these drugs are excreted into human bile in sufficient quantities and in an active form they may be able to enhance the speed of cholesterol gallstone dissolution therapy.
Influence of ophthalmic formulations on sodium cromoglycate disposition in the albino rabbit eye
Authors: Shrewsbury Robert P , Swarbrick James , Newton Kimberly S , Riggs Linda C 
Published: April 2011

Abstract
The effect of different ophthalmic vehicles on the disposition of sodium cromoglycate in tears and ocular tissues of the rabbit eye has been studied over 6 h. The vehicles contained sodium cromoglycate, 2% in an aqueous solution, 2 and 4% in an oleaginous formulation of polyethylene and mineral oil (Plastibase 5W), and 4% in an absorption ointment base of 10% hypoallergenic acetylated lanolin (Modulan) in paraffins. The last formulation was superior to all others studied over 6 h in prolonging the retention of sodium cromoglycate in the precorneal area and the conjunctiva. The concentration of sodium cromoglycate in the tears, conjunctiva and cornea 6 h after administration of the acetylated lanolin base equalled or exceeded the concentrations obtained with the aqueous solution 1 h post-instillation.
Cardiodepressant effects of ethanol on guinea-pig atria: presynaptic and postsynaptic components
Authors: Mantelli Laura , Corti Vittorio , Ledda Fabrizio 
Published: April 2011

Abstract
Ethanol, at concentrations ranging from 0.5 to 1.5%, depressed myocardial contractility of electrically-stimulated guinea-pig atria. This effect was evident in preparations bathed with a low calcium concentration, but was progressively reduced by increasing the extracellular calcium. The same concentrations of ethanol produced a dose-dependent inhibition of the cardiac response to field stimulation of the adrenergic nerve terminals. This effect was again calcium-dependent. These results support the hypothesis that the pre- and postsynaptic components of the cardiodepressant effects of ethanol are due to a reduction in calcium availability both at the nerve endings and in the contractile cells.
Amiodarone does not affect digoxin kinetics in the rabbit
Authors: Buss D C , Routledge P A 
Published: April 2011

Abstract
It has been reported that amiodarone may interact with digoxin in man. We investigated the effects of amiodarone pretreatment (35 mg kg−1 day−1) on the pharmacokinetics Of a single dose of digoxin (50 μg kg−1) in 6 rabbits. Total body clearance of digoxin was 138.84 ± 44.67 and 147.99 ± 29.17 ml min−1, serum half life 187.9 ± 60.9 and 181.34 ± 25.57 min and volume of distribution 35.4 ± 8.54 and 37.8 ± 3.9 litres before and after amiodarone treatment, respectively. None of these changes were statistically significant. We conclude that the presence of an amiodarone-induced change in digoxin pharmacokinetics in the rabbit was not evident and that other animal models will be necessary for studying this interaction.
A strain dependent sex difference in ouabain-induced cardiotoxicity in rats
Authors: Wilson S A , Hewick D S 
Published: April 2011

Abstract
Male rats of the BDIX strain were about twice as sensitive to the lethal effects of intravenously infused ouabain than were their female counterparts. This sex difference in ouabain sensitivity was not exhibited by rats of the Wistar strain. In bile duct-cannulated animals, ouabain biliary excretion was much faster in female BDIX rats. This finding could partly explain the greater ouabain resistance, although certain aspects of the cardiac/plasma ouabain concentration data aid suggest that there may have been a component of the sex-related resistance that was not explicable on a pharmacokinetic basis. The faster ouabain biliary excretion in female rats could also partly explain the fact that for similar rates of infusion, the plasma ouabain concentration during infusion was similar in both sexes, despite the body size of the female rats being about one-third smaller.
The influence of conformational factors on the metabolic conjugation of aryloxyacetates
Authors: Van De Waterbeemd Han , Testa Bernard , Caldwell John 
Published: April 2011

Abstract
Among p-chlorophenoxyalkanoic acids, the acetate and 2-propionate are essentially inert towards metabolic conjugation, whereas the isobutyrate (clofibric acid) undergoes extensive glucuronidation, as well as amino acid conjugation in carnivores. To try to explain these differences, the conformational behaviour of three model compounds was studied by quantum mechanical calculations (PCILO method). All three compounds prefer syn (folded) conformers, but the isobutyrate, in contrast to its two lower homologues, also has anti (extended) conformers of relatively low energy. Based on these results, a hypothetical topographical model is proposed for the binding site of glucuronyltransferase.
Can the effects of meptazinol on the guinea-pig isolated ileum be explained by inhibition of acetylcholinesterase?
Authors: Ennis Christine , Haroun Faizal , Lattimer Norman 
Published: April 2011

Abstract
It has previously been shown that there is a cholinergic component in the antinociceptive action of the opioid analgesic drug meptazinol. In the present study meptazinol was shown to be an inhibitor of acetylcholinesterase in-vitro with a potency one hundredth that of physostigmine. This activity was found to reside only in the (−)-enantiomer of meptazinol. The anticholinesterase activity of meptazinol may explain the increase in the size of the electrically-evoked contraction of the guinea-pig isolated ileum preparation since by using a long pulse width (5 ms) it was found that the (−)-enantiomer of meptazinol modified only the component of the response due to neuronally released acetylcholine and had no direct effect on the smooth muscle. This property of meptazinol may also be responsible for the cholinergic effects of the drug in-vivo.
Dose-related effects of ethylketazocine on nociception, behaviour and autonomic responses in the horse
Authors: Kamerling Steven G , Dequick David J , Weckman Timothy J , Tobin Thomas 
Published: April 2011

Abstract
Sensitive methods for measuring the analgesic, physiological and behavioural effects of opioids in the horse have recently been developed. Fentanyl, a prototypic μ-opiate receptor agonist, has been previously shown to produce a syndrome characterized by marked analgesia and locomotor stimulation as well as tachycardia, tachypnoea and behavioural arousal. To determine whether other opiate receptors mediate some of the actions of the narcotic analgesics in the horse, an agent with activity at κ and to a lesser extent μ-receptors was studied using a vigorous experimental protocol. Like fentanyl, ethylketazocine (EKC) (1.0025–1.012 mg kg−1 i.v.) produced marked dose-related analgesia to noxious thermal stimuli. Modest dose-related increases in locomotor activity, pupil diameter and rectal temperature were also observed. However, in contrast to fentanyl, EKC failed to produce any change in cardiac or respiratory rates and produced behavioural sedation rather than arousal. These data suggest that μ- and possibly κ-receptors can mediate the actions of narcotics in the horse.
Evidence that 6-hydroxydopamine is an inhibitor of catechol-O-methyltransferase in intact tissue
Authors: Reid Julianne J , Stitzel Robert E , Head Richard J 
Published: April 2011

Abstract
The effect of in-vitro sympathetic denervation on the O-methylation of 2-hydroxyoestradiol was examined using the rabbit thoracic aorta. Aortic segments were exposed to 6-hydroxydopamine (400 mg litre−1, 10 min), incubated in 2-hydroxyoestradiol (5 μm, 60 min), and the 2-methoxyoestradiol formed was quantified using HPLC with electrochemical detection. Pre-exposure to 6-hydroxydopamine reduced O-methylation by 90% in intact aortic strips. However, O-methylation was also reduced (81%) in rabbit aorta that had been surgically denervated before exposure to 6-hydroxydopamine. Furthermore, the O-methylation of 2-hydroxyoestradiol (20 μm, 15 min) by partially purified soluble catechol-O-methyltransferase was inhibited by 6-hydroxydopamine (400 μg litre−1) by 95% and 51% in the absence and presence of antioxidant, respectively. These results suggest that the inhibition of catechol-O-methyltransferase by 6-hydroxydopamine reported for the purified enzyme, applies to the intact tissue and that the inhibition is dependent on oxidation of the 6-hydroxydopamine. Subsequent experiments using dialysis techniques demonstrated that the inhibition of soluble catechol-O-methyltransferase by 6-hydroxydopamine was irreversible in part, but the degree of irreversibility was influenced by pH and by the extent of in-vitro oxidation of 6-hydroxydopamine.
Dose versus survival time curves in the evaluation of ‘prompt’ and ‘delayed’ acute toxicities
Authors: Molinengo L , Orsetti M 
Published: April 2011

Abstract
The acute toxicity of arecoline, diisopropylfluorophosphate, nicotine and pilocarpine alone or in association with atropine has been evaluated from percentage lethality and from the linear correlation of (doses/(survival time)) vs doses. The experimental points obtained with arecoline and diisopropylfluorophosphate, alone or in association with atropine 50 mg kg−1, are apparently ordered according to two straight lines. That at lower doses gave the LD50 values of the compounds studied. The values found are comparable to those found with percentage lethality. The straight line found at high doses may indicate that over certain doses the drugs kill by a different mechanism. It is concluded that the evaluation of the survival time may be a reliable method in identifying and in evaluating quantitatively the two forms of toxicity.
Similarity in the aldehyde oxidases from guinea-pig liver and polymorphonuclear leucocytes
Authors: Beedham C 
Published: April 2011

Abstract
Partially purified enzyme from guinea-pig leucocytes has been shown to have properties similar to both guinea-pig and rabbit liver aldehyde oxidase. The presence of molybdenum in the leucocyte enzyme has been demonstrated and substrate oxidation by either guinea-pig enzyme was found to be completely inhibited by menadione, a potent inhibitor of rabbit liver aldehyde oxidase. The leucocyte enzyme resembles the guinea-pig liver enzyme in terms of substrate specificity but there is considerable variation in substrate oxidation rates between the two species.
A vacuum microbalance technique for studies on the wettability of powders
Authors: Buckton G , Beezer A E , Newton J M 
Published: April 2011

Abstract
A vacuum microbalance technique has been used to evaluate the wettability of powders. The rate of uptake, and equilibrium weight of uptake, of water vapour onto outgassed powder samples, of differing wettabilities, were determined at different known temperatures. Standard techniques of data analysis were used to establish the enthalpy, entropy and Gibb's free energy of the activation and adsorption processes. The values obtained appeared to be in the correct order of magnitude and those for activation clearly reflected the relative wettability of the powders. Tests for compensation demonstrated that with the exception of phenobarbitone, there was probably a common mechanism producing the adsorption.
Antihistamine-sensitive active vasodilatation in the perfused hindquarters of the rat
Authors: Holcslaw Terry L , Randall Robert D 
Published: April 2011

Abstract
The innervated, constant flow perfused hindquarters of the rat have been used to evaluate post-stimulation vasodilatation, which is a model of active reflex vasodilatation in this species. The vasodilatation resulting from lumbar sympathetic stimulation was dependent on stimulation frequency and duration. Maximal vasodilatation (16 ± 2%) was at 8 Hz for 15 s, while markedly reduced vasodilatation was seen after stimulation for longer than 30 s at all frequencies tested. The vasodilatation was transient. Atropine (2.0 mg kg−1 i.v.) failed to attenuate post-stimulation vasodilatation at a time when hindquarter vasodilatation to i.a. acetylcholine had been abolished. The H1 antihistamine, tripelennamine (2.5 mg kg−1 i.v.) significantly reduced (77%) post-stimulation vasodilatation relative to controls at a time when hindquarter vasodilatation due to i.a. histamine was essentially abolished. Reactive hyperaemia is an unlikely cause of vasodilatation since it is not blocked by H1 antihistamines; 60 s post-occlusion hyperaemia also, was not demonstrable. These data suggest that there is an active component of baroreceptor-mediated vasodilatation in the rat and that histamine, rather than acetylcholine, could be a mediator of this vasodilatation.
The pH-dependence of chloroquine uptake by phosphatidylcholine vesicles
Authors: Ferrari V , Cutler D J 
Published: April 2011

Abstract
The pH-dependence of chloroquine uptake by phosphatidylcholine bilayered vesicles was investigated to examine the relative affinity of ionized and un-ionized chloroquine species to membrane bilayers. The results suggest that the neutral species and monocation are taken up by the bilayers but only the un-ionized species interacts significantly with the hydrocarbon interior.
Direct measurements on individual microcapsule dissolution as a tool for determination of release mechanism
Authors: Hoffman A , Donbrow M , Benita S 
Published: April 2011

Abstract
A method is described for simultaneous microscopic observation of individual microcapsule core material dissolution together with quantitative measurement of the individual kinetics of release of the contents. These may be conductimetric in the case of ionized materials or spectro-photometric otherwise. This enables correlation of changes in core surface area during dissolution with kinetics. Surprisingly, both ethyl cellulose- and polymethacrylatecoated cores of potassium dichromate crystals, used as a model, showed localized internal dissolution universally, providing evidence of the exit of the salt via pores in the membrane, in spite of the kinetics being invariably zero order, as expected for individual microcapsules. The advantages of the method are presented.
Evidence against VIP-involvement in neurogenic relaxations of the mouse anococcygeus muscle
Authors: Carvajal A , Gibson A , Yu O 
Published: April 2011

Abstract
Vasoactive intestinal polypeptide (VIP) antiserum, α-chymotrypsin, and repeated exposure to VIP markedly reduced relaxations of the mouse anococcygeus muscle to VIP but not to field stimulation. This evidence suggests that VIP does not mediate non-adrenergic, non-cholinergic relaxations in the mouse anococcvpeus.
Effect of particle size and food on gastric residence time of non-disintegrating solids in beagle dogs
Authors: Itoh Tomoh , Higuchi Takeru , Gardner Colin R , Caldwell Larry 
Published: April 2011

Abstract
The gastric residence times of various sizes of radio-opaque particles and tablets were measured in beagle dogs by X-ray, both in the fasted state and after a single meal. During the course of the studies, changes in intragastric pH were also monitored with a radiotelemetric pH sensor, the Heidelberg capsule. The gastric residence time increased with increasing particle size and with particles ≥5 mm in diameter approached a plateau value both in the fasted state and after feeding. This value was about 7.5 h after feeding and about 1.5 h in the fasted state, and probably corresponded to the occurrence of the interdigestive migratory myoelectric complex (IMMC wave). The pH in the stomach was variable in the fasted state, but an abrupt pH increase (up to pH 6–7) was observed during the emptying of larger tablets. In some instances this high pH in the stomach was maintained until the next IMMC wave occurred. The gastric emptying of larger tablets administered with food was alo associated with an abrupt pH increase.
Detection of endotoxin in mice by measurement of endotoxin-induced changes in plasma concentrations of zinc and of the acute-phase protein serum amyloid P-component
Authors: Poole S , Das R E Gaines , Baltz M , Pepys M B 
Published: April 2011

Abstract
Preparations of six bacterial endotoxins reduced plasma concentrations of zinc and increased concentrations of the acute-phase protein serum amyloid P component (SAP) in mice. The changes were sufficiently sensitive to permit use of either response in tests for endotoxin and hence for pyrogenic contamination.
Modification of electrical field stimulation-induced contractions in the guinea-pig ileum by metoclopramide and ICS 205–930 depends on the integrity of the mucosa
Authors: Costall B , Gunning S J , Naylor R J , Tattersall F D 
Published: April 2011

Abstract
Contractions induced by electrical field stimulation of guinea-pig ileum longitudinal muscle strips were enhanced by metoclopramide and ICS 205–930 at concentrations similar to those required to antagonize at 5-hydroxytryptamine ‘M’ receptors. The enhancement of contraction was observed in intact ileum strips but was not recorded in the longitudinal muscle myenteric plexus preparation or from the ileum with the mucosal layer removed. It is concluded that an intact mucosal layer is required for metoclopramide and ICS 205–930 to enhance electrical field stimulation-induced contractions of the guinea-pig ileum.
Rapid drug haptenization procedure: application to gentamicin and quinidine
Authors: Regan Ciaran M 
Published: April 2011

Abstract
A rapid and simple drug conjugation procedure which utilizes the heterobifunctional reagent N-hydroxysuccinimidyl 6-(4′-azido-2′-nitrophenylamino)hexanoate is described. With this protocol two drugs of diverse structure and solubility have been successfully haptenized. Rabbits immunized with these conjugates yielded drug-specific antibodies as judged by a solid phase radioimmunoassay. Furthermore, using this technique, no cross-reactivity could be detected. Such haptens also elicited an immune response in mice thus further extending their potential for the production of drug specific monoclonal antibodies.
Tissue cholinesterase inhibition by propranolol and related drugs
Authors: Alkondon M , Ray A , Sen P 
Published: April 2011

Abstract
The effect of (±)-propranolol and some related drugs have been investigated on the cholinesterase (ChE) enzyme activity of heart and brain tissues of the rat. Brain homogenates hydrolysed more methacholine than benzoylcholine and the reverse was true for the heart tissue. In-vitro, (±)-, (+)- and (−)-propranolol, as well as its quaternary analogue, UM-272, all significantly inhibited heart and brain ChE. Timolol and sotalol, however, were less potent. In-vivo, (±)-propranolol (30 μmol kg−1) significantly inhibited brain ChE activity in rats when compared with saline controls. It is inferred that propranolol inhibits brain and heart ChE enzyme in a non-stereoselective manner and that this cholinomimetic action could be involved in the mediation of some of its therapeutic effects.
Effect of adrenergic drugs on the isolated colon of Rhesus cynomolgus
Authors: Grivegnée A R , Fontaine J 
Published: April 2011

Abstract
The effects of adrenaline, noradrenaline, isoprenaline and dopamine were studied on the longitudinal muscle of the ascending and descending colon of the rhesus monkey. All these drugs induced a relaxation of the preparation, dopamine being the less active agonist. The responses seem to be the result of β2-adrenoceptor stimulation since their inhibition by practolol (β1) is weaker than their inhibition by propranolol (β1 and β2 dopaminergic). There is no evidence for the presence of dopaminergic receptors in this preparation.
Amethocaine-induced inhibition of mitochondrial monoamine oxidase activity
Authors: Haque S J , Poddar M K 
Published: April 2011

Abstract
Amethocaine (tetracaine) (1–10 μM) produces a concentration-dependent in-vitro inhibition of mitochondrial membrane-bound MAO activity towards tyramine (18–84% in brain and 19–84% in liver) and 5-hydroxytryptamine (5-HT) (23–94% in brain and 20–100% in liver). At relatively higher concentrations (25–300 μM) of amethocaine, benzylamine oxidation is inhibited in brain (24–91%) and liver (29–100%). The extent of MAO inhibition is appreciably reduced when preincubation time of the enzyme with a low concentration (7.5 μM) of amethocaine is increased from zero to 45 min. This inhibition is reversible. The Km of MAO for tyramine is increased in brain (106–473%) and liver (121–352%) in the presence of amethocaine (2–7.5 μM) accompanied by a decrease in Vmax (21–51% in brain and 18–57% in liver). Similarly the Km of MAO for 5-HT is increased to the extent of 79–336% in brain and 51–225% in liver and the corresponding Vmax is decreased by 35–55% and 39–74%, respectively, in the presence of 2–5 μM amethocaine. At relatively higher concentrations (25–100 μM), amethocaine increases the Km of MAO for benzylamine in brain (25–101%) and liver (26–85%) and decreases the Vmax by 28–64% and 32–63% in the respective tissues. Thus these results suggest that amethocaine preferentially inhibits MAO-A and the nature of inhibition is reversible and of mixed type.