bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cultured neonate rat myocytes as a model for the study of myocardial ischaemic necrosis
Authors: HIGGINS TREVOR J C , BAILEY PETER J , ALLSOPP DAVID , IMHOF DERYL A 
Published: April 2011

Abstract
The preparation of cultures of neonate rat heart muscle cells is described. These cultures, when subjected to anoxia, show enzyme release that can be directly related to the uptake of a vital dye such as trypan blue. Enzyme release is a valid method of estimating cell necrosis in this model. The survival of anoxic cultures is closely associated with glycolytic activity. Glycolysis rate falls and enzyme release increases as the medium glucose concentration is reduced. If glycolysis is inhibited by either 2-deoxyglucose or L-lactate, enzyme release under anoxic conditions is enhanced. Enzyme release correlates inversely with glycolytic activity and the intracellular ATP content of the cultures. Addition of ATP to anoxic cultures partially ameliorates the effect of the anoxia on enzyme release. Elevation of the calcium content of the culture medium exacerbates the damage caused to cardiac myocytes by anoxic insult. This effect can be obtunded by calcium-antagonist drugs such as verapamil or nifedipine and can be explained in terms of a reduction in utilization of intracellular ATP by the anoxic myocytes. These observations indicate that cultured myocytes may represent a useful model of hypoxic injury against which novel pharmacological agents, that may reduce hypoxic or ischaemic injury in vivo, could be evaluated.
Pharmacological reactivity of granulation tissue
Authors: GARCÍA-VALDECASAS J C , GARCÍA-VALDECASAS F , PERA C 
Published: April 2011

Abstract
The contractile system of the myofibroblast has well defined characteristics. The findings suggest the presence of 5-hydroxytryptaminergic as well as α and β-adreno-receptors, although both appear to be immature. It does not have cholinergic or histaminergic receptors. The contractile system is inhibited by cytochalasin B and is not sensitive to colchicine. The contractile machinery is suggested to be the microfilament system, as it occurs in the contractile apparatus of primitive cells. This is in accordance with the role of myofibroblasts in granulation tissue neoformation.
Noradrenergic component in the vasoconstriction induced by 5-hydroxytryptamine in goat cerebral arteries
Authors: MARIN J , SALAICES M , GÓMEZ B , LLUCH S 
Published: April 2011

Abstract
5-Hydroxytryptamine (5-HT) elicited dose-dependent increases in tension in the middle cerebral artery of the goat, which were significantly antagonized by lysergic acid diethylamide (LSD, 10−8 M) and methysergide (10−7 M). In the presence of phentolamine (10−6 M), the dose-response curve to 5-HT was shifted to the right, the pA2 value for this antagonism was 6·52. Pretreatment of goats with reserpine (0·02 mg kg−1 day−1 for three days) or removal of both superior cervical ganglia 15 days before the experiment brought about a significant decrease in the vasoconstriction induced by doses of 5-HT higher than 10−7 M. The remaining contraction produced by 5-HT in arterial segments from reserpinized or gangliectomized goats was further reduced in the presence of LSD. In addition, high concentrations of 5-HT induced tritium release from goat pial arteries preloaded with (−)-[3H]noradrenaline, 2 × 10−7 M) which was significantly decreased in vessels from gangliectomized or reserpinized goats. These results in goat cerebral arteries indicate that in the contraction evoked by 5-HT there are two components. The first appears with low concentrations (up to 10−7 M) in which 5-HT acts directly on 5-HT receptors. The second occurs at high doses (&gt;10−7 M) in which 5-HT also acts indirectly on α-adrenoceptors by release of noradrenaline from noradrenergic nerve endings.
Altered ocular absorption and disposition of sodium cromoglycate upon ion-pair and complex coacervate formation with dodecylbenzyldimethylammonium chloride
Authors: WILSON C G , TOMLINSON E , DAVIS S S , OLEJNIK O 
Published: April 2011

Abstract
Ion-pair formation between the dianionic drug sodium cromoglycate and dodecylbenzyldimethylammonium chloride has been found to alter the extent and rate of corneal penetration of both large ions upon their coadministration. Additionally, using a complex coacervate of the two large ions as the applied dose form (in which the complex is in equilibrium with the ion pairs), a change in the overall disposition of both large ions to the various components of the eye is observed.
Differential blockade of pre- and postsynaptic α-adrenoceptors by the 2-R and 2-S enantiomers of WB4101
Authors: MOTTRAM DAVID R 
Published: April 2011

Abstract
Agonists and antagonists of the α-adrenoceptor have been shown to possess different degrees of potency at the pre- and postsynaptic levels. The present investigation was undertaken to see whether the two optical isomers of WB4101 likewise exhibit differential blockade at the two receptor sites. This was achieved by measuring the potencies of 2-R and 2-S WB4101 against noradrenaline-induced contractions of the rat isolated vas deferens and against clonidine-induced inhibition of the twitch response in field stimulated rat vas deferens. Results showed that though the enantiomers exhibited widely differing potency, as indicated by calculations of pA2 values, at the postsynaptic level, they possessed almost identical potency presynaptically. In addition, 2-aminomethyl-1, 4-benzodioxan itself both exhibited reasonable presynaptic α-adrenoceptor blocking activity, whilst being devoid of activity postsynaptically. The values for slope on the Schild plots for 2-R and 2-S WB4101 indicated that they produced classical competitive antagonism at the postsynaptic receptor but at the presynaptic level the values for slope were indicative of a non-competitive type of blockade. Results are discussed in terms of recent suggestions of that agonists and antagonists of the α-adrenoceptor may not share a common mechanism or site of action at the presynaptic level.
Age-related changes in the chronotropic effect and the enzymic decarboxylation of L-threo-3,4-dihydroxyphenylserine in the rat heart
Authors: ARAKI HIROMASA , FUJIWARA HIROSHI , TANAKA CHIKAKO 
Published: April 2011

Abstract
The cardiac effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) and the enzymatic decarboxylation of the drug by L-aromatic amino acid decarboxylase (AADC) were studied in atria isolated from rats ranging in age from newborn to adults and the findings compared with the cardiac effect of noradrenaline (NA). L-threo-DOPS produced dose-dependent, slow-onset and positive chronotropic effects in atria from rats of different ages. Its effect was inhibited in atria from benserazide-treated rats, suggesting that the effects are due to NA formed from L-threo-DOPS by enzymic decarboxylation rather than to the compound itself. Chronotropic sensitivity to L-threo-DOPS was highest in the newborn and decreased with age during the first 3 weeks of life. The development of cardiac response to it correlated well with the development of enzymic decarboxylation of the drug but did not correlate with the developments of chronotropic sensitivity to NA and of NA concentrations in the heart. These findings suggest that in newborn rats, L-threo-DOPS is effectively converted by AADC to NA which in turn acts on β-receptors in the pacemaker cell membrane.
In vitro dissolution of dapsone
Authors: SWARBRICK JAMES , MA DIANA 
Published: April 2011

Abstract
Log normal samples of dapsone (DDS) were prepared in which the geometric mean diameter ranged from 20 to 50 μm while the geometric standard deviation was in the range 1·62 to 1·88. Using a simple in vitro flow-through dissolution cell at 37°C, the data obtained were found to fit the Hixson-Crowell cube root dissolution law up to a critical time, Tc, where a distinct break occurred. Such a biphasic phenomenon has been predicted by other workers and is related to the time at which the smallest particles present have undergone dissolution. The initial slopes of the cube root dissolution plots were shown to be directly related to the reciprocal of the geometric mean diameter.
Distribution of daunorubicin, a potent in vitro trypanocide which lacks in vivo activity, in the blood of trypanosome-infected mice
Authors: BROWN J E , BROWN J R , WILLIAMSON J 
Published: April 2011

Abstract
Daunorubicin is a highly potent trypanocide in vitro but lacks significant in vivo activity. Distribution of the drug in the blood components and in trypanosomes from mice infected with Trypanosoma rhodesiense was therefore examined. Drug is accumulated in the trypanosomes in a similar manner to, but to a greater extent than, its accumulation in platelets; it is, however, taken up by erythrocytes to a much smaller extent. Drug concentrations in trypanosomes, platelets and erythrocytes declined with its decline in plasma whereas in white blood cells the drug was retained at a constant level. Daunorubicin concentrations in plasma were several orders of magnitude higher than the in vitro trypanocidal concentration. Fluorescence microscopy showed that although daunorubicin reaches the trypanosome nucleus, its concentration decreases rapidly so that adequate levels of drug may not be sustained in the bloodstream form of the organism for a sufficient length of time to give a trypanocidal effect in vivo.
Prenylamine and the myocardial response to ischaemia and reperfusion: effects of acute and chronic treatment
Authors: MANNING ALLAN S , SHATTOCK MICHAEL J , HEARSE DAVID J 
Published: April 2011

Abstract
The ability of prenylamine gluconate (Segontin) to influence the extent of myocardial ischaemic injury was investigated in the isolated ‘working’ rat heart preparation. The drug was administered either acutely alone (4 μM litre−1 in the perfusion medium) or chronically plus acutely in which case animals were pre-treated (10 mg kg−1 day−1 orally) for 10 days and the drug was then also added (4 μM litre−1) to the perfusate. Acute administration alone resulted in a small reduction in spontaneous functional performance of the aerobic isolated heart in comparison with gluconate treated controls. It also increased the percentage of hearts able to recover functional activity after a period of severe ischaemia and decreased ischaemia induced injury as assessed by enzyme leakage. In contrast to the acute results the combination of chronic and acute administration of prenylamine did not significantly alter spontaneous cardiac function. Although a small increase in the number of hearts that recovered function was apparent, there was a concomitant decrease in post-ischaemic functional performance with no reduction of ischaemia induced enzyme leakage.
The permeability of enteric coatings and the dissolution rates of coated tablets
Authors: PORTER S C , RIDGWAY K 
Published: April 2011

Abstract
The effect of an increasing concentration of plasticizer and pigment on the permeability to both water vapour and simulated gastric juice of cellulose acetate phthalate and polyvinyl acetate phthalate has been evaluated. There were significant differences between the permeability coefficients of each polymer, particularly with regard to water vapour. The presence of additives within the film coatings had a greater effect on the properties of cellulose acetate phthalate than those of polyvinyl acetate phthalate. Suitable formulations of each polymer were used to enteric coat 325 mg aspirin tablets, which were subsequently subjected to both the Disintegration Test for Enteric Coated Tablets B.P. and a dissolution procedure to monitor the release of drug in simulated gastric juice and simulated intestinal fluid. Both polymers demonstrated their suitability for producing enteric coatings. However, polyvinyl acetate phthalate yielded a faster release of aspirin in simulated intestinal fluid than did cellulose acetate phthalate.
Effect of (+)- or (−)-enantiomers of fenfluramine or norfenfluramine on nutrient selection by rats
Authors: HIRSCH JOSEPH A , GOLDBERG SCOT , WURTMAN RICHARD J 
Published: April 2011

Abstract
The effects of the (+)- and (−)-enantiomers of fenfluramine and norfenfluramine on food choice and total food consumption by rats, have been examined. Animals were trained to select their food during an 8-h daily interval from two isocaloric-isocarbohydrate (40%) diets differing in protein contents (5 or 45% casein). Low doses of (+&gt;-fenfluramine (1.25 or 1.65 mg kg−1) selectively reduced consumption of the 5%-protein diet during the hour after administration, thereby also reducing carbohydrate intake by a greater proportion than protein intake. Higher doses (2.5 or 4.0 mg kg−1) diminished consumption of both test diets to an equivalent extent. (+&gt;-Norfenfluramine, although anorectic, did not modify the relative consumptions of carbohydrate and protein at any dose tested. These observations affirm that nutrient selection as well as total food consumption can be altered by drugs affecting particular neurotransmitters.
On the ability of domperidone to selectively inhibit catecholamine-induced relaxation of circular smooth muscle of guinea-pig stomach
Authors: SAHYOUN H A , COSTALL B , NAYLOR R J 
Published: April 2011

Abstract
The effects of noradrenaline and dopamine, and their interactions with α- and β-adrenoceptor antagonists and with domperidone, were studied on circular smooth muscle strips taken from the cardia, fundus, body and antrum of the guinea-pig stomach. Noradrenaline and dopamine caused relaxations of all tissues which were generally susceptible to antagonism by either propranolol or phentolamine in concentrations shown to antagonize the relaxations caused by isoprenaline or phenylephrine respectively. In addition, dopamine, in concentrations subthreshold for relaxation, caused contraction of the muscle strips which increased in intensity from the cardia to the antral region: these contractions were antagonized by phentolamine and yohimbine but were insensitive to prazosin: prazosin selectively inhibited the phenylephrine relaxations. With the exception of a modest reduction in the responses of the cardia to dopamine, all tissue responses to noradrenaline and dopamine were resistant to reserpine. Domperidone and haloperidol were found to selectively inhibit the phenylephrine- noradrenaline- and dopamine-induced relaxations of the stomach strips and to enhance the contractile component of dopamine's action: this ability of domperidone to facilitate a dopamine induced contraction, which was most marked in the body and antral regions, was prevented by phentolamine. It is thus concluded that domperidone antagonizes noradrenaline- and dopamine-induced relaxations at one adrenoceptor site having characteristics conistent with an α1-adrenoceptor type whilst failing to antagonize at a further dopamine-sensitive adrenoceptor site involved in contraction of circular smooth muscle of the stomach and having characteristics consistent with an α2-adrenoceptor.
Stereospecificity of behavioural effects of viloxazine in bulbectomized rats does not correlate with its 5-HT-releasing action in vitro
Authors: GREENWOOD D T , KEMP JANET D , MIDDLEMISS D N 
Published: April 2011

Abstract
The effects of the antidepressant drug viloxazine and its two optically active isomers on the passive avoidance learning deficit surgically induced in rats by bilateral bulbectomy have been determined. Fourteen consecutive daily injections of either the racemate or the S-isomer (2, 5 and 10 mg kg−1 i.p.) significantly improved the acquisition of avoidance behaviour. The R-isomer was devoid of such activity in this same dose range. The various isomeric species of viloxazine were also studied in vitro for their ability to induce a release of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT) from rat brain slices. In agreement with previous reports, racemic viloxazine caused a concentration-dependent (10−5 − 10−3 M&gt; release of 5-HT without affecting any significant change in the release of either catecholamine. However, in contrast to the results of the behavioural studies, this phenomenon did not exhibit stereospecificity, all three isomeric forms being equally active. Thus, there is no simple relationship between viloxazine's behavioural activity in bulbectomized rats and its 5-HT releasing properties observed in vitro. The significance of these findings with respect to previously reported effects of the drug indicative of facilitation of central 5-HT mediated processes is discussed.
Effects of cyclodextrins on the acid hydrolysis of digoxin
Authors: UEKAMA K , FUJINAGA T , HIRAYAMA F , OTAGIRI M , KURONO Y , IKEDA K 
Published: April 2011

Abstract
The effects of three cyclodextrins (α-, β-, γ-CyD) on the acid hydrolysis of digoxin were examined. From the high performance liquid chromatographic tracing of each of the four components (digoxin, bisdigitoxoside, monodigitoxoside, digoxigenin) in reaction mixtures, the individual rate constants (k1-k6) were determined by analogue computer simulation. The hydrolysis was suppressed by CyDs in the order of β-&gt;γ-&gt;α-CyD, where β-CyD inhibited the appearance rates of digoxigenin (k3, k5, and k6) significantly. In the dissolution study of digoxin tablets, the increase in dissolution rate and decrease in acid hydrolysis were attained by inclusion complexation. The data are presented suggesting that CyDs are useful for improving the oral bioavailability of digoxin.
Are the prejunctional histamine receptors on sympathetic nerve terminals in guinea-pig isolated atria activated during anaphylaxis in vitro?
Authors: WONG-DUSTING H , STORY D F , RAND M J 
Published: April 2011

Abstract
In isolated atria from sensitized guinea-pigs, antigenic challenge with ovalbumin induces an anaphylactic reaction in which there is an increased rate and force of contraction. At the same time, stimulation-induced release of [3H]noradrenaline is inhibited by 40%. Cimetidine decreased the tachycardia occurring during anaphylaxis but had no effect on the inhibition of stimulation-induced transmitter release. It is known that antigenic challenge of sensitized guinea-pig atria releases histamine from mast cells; this histamine acts postjunctionally to increase heart rate. However, the inhibition of noradrenergic transmitter release is not due to the stimulation of prejunctional inhibitory histamine receptors.
Practical implications of theoretical consideration of capsule filling by the dosator nozzle system
Authors: JOLLIFFE I G , NEWTON J M 
Published: April 2011

Abstract
Eight lactose size fractions with mean particle sizes ranging from 15.6 to 155.2 μm were characterized by their failure properties using a Jenike shear cell. The effective angle of internal friction was found to be constant for all size fractions, with a mean value of 36.2°. Jenike flow factors could only be obtained for the two most cohesive size fractions presumably due to limitations of the shear cell. Angles of wall friction, ϕ, were determined for all size fractions on face ground and turned stainless steel surfaces. These decreased with increasing particle size up to around 40 μm, above which they became effectively constant for both surfaces. The rougher turned plate gave consistently higher values of ϕ for each particle size. Simple retention experiments with a dosator nozzle and a range of powder bed bulk densities showed good retention was possible only up to a particle size of around 40 μm. Retention was difficult or impossible above this size. Values of ϕ were applied to equations derived in the theoretical approach described previously (Jolliffe et al 1980). This showed that the strength required within a powder to ensure arching increases with increasing particle size up to around 40 μm. Above this size, this strength requirement becomes constant. This is related to the powder retention observations. Finally, the failure data was used to calculate the minimum compressive stresses required to ensure powder retention within the dosator nozzle, by employing the equations described by Jollife et al (1980). This suggested that, as powders became more free flowing, a larger compressive stress is necessary and that the angle of wall friction should be lower to ensure stress is transmitted to the arching zone.
Incidence of experimental cirrhosis on hepatic disposition of [3H] levamisole in rats
Authors: GALTIER P , COCHE Y , CAMGUILHEM R 
Published: April 2011

Abstract
Levamisole [phenyl-2 3H] was injected intravenously (4.7 mg kg−1) into anaesthetized controls and rats in which cirrhosis had been induced by a combination of carbon tetrachloride and phenobarbitone. The biliary excretion (6 h) of the parent drug and its metabolites formed a significant part of the administered dose. Although bile flow did not vary, biliary excretion of levamisole and metabolites were respectively increased and decreased in cirrhotic compared with control animals. These differences could be the result of cirrhosis-induced decrease in the hepatic biotransformation of levamisole and also to limited active carrier transport for the output of metabolites into bile canaliculi.
Catecholamine-induced relaxation and contraction of the lower oesophageal and pyloric sphincters of guinea-pig stomach: modification by domperidone
Authors: SAHYOUN H A , COSTALL B , NAYLOR R J 
Published: April 2011

Abstract
Catecholamine control of circular smooth muscle activity of the lower oesophageal (LOS) and pyloric sphincters (PS) of the guinea-pig was studied using α- and β-adrenoceptor agonists and antagonists. In both sphincters dopamine (DA) and noradrenaline (NA) caused relaxation followed by contraction of the circular smooth muscle, although the ability of NA to contract the PS was weak and inconsistent. Isoprenaline relaxed both sphincter preparations but, whilst phenylephrine contracted the muscle of the PS, it caused a biphasic relaxation-contraction of the LOS. The use of the α- and β-adrenoceptor antagonists, phentolamine and propranolol, indicated that contractions of both sphincters by NA and DA involved an α-type adrenoceptor whilst relaxation was mediated via a β-adrenoceptor (PS) or via both α- and β-adrenoceptors (LOS). Use of the α1 and α2 antagonists, prazosin and yohimbine, indicated that the α-adrenoceptor type involved with both the contractions and relaxation was α1. Both domperidone and haloperidol antagonized the contractile responses of both tissues to DA (and partly the relaxation of the LOS) but were similarly effective against the contractions induced by NA and phenylephrine; an effect on α1-adrenoceptors was therefore concluded. In selectively antagonizing the contractile effects of DA in the PS, domperidone enhanced DA's ability to relax this sphincter.
Effect of particle size on the compaction mechanism and tensile strength of tablets
Authors: MCKENNA A , MCCAFFERTY D F 
Published: April 2011

Abstract
The effect of particle size variation on tablet tensile strength for spray-dried lactose, Sta-Rx 1500 and Avicel PH-101 was investigated. Decreasing the particle size of spray-dried lactose and Sta-Rx 1500 resulted in stronger compacts whereas the tablet tensile strength of Avicel PH-101 was unaffected by particle size variation. The Heckel relationship, at two different contact times, was used to examine the predominant compaction mechanism. This was independent of the size fractions studied for all three materials. Angle of repose and Hausner ratio measurements indicated a correlation between the internal forces of friction and cohesion of the sized powders and the tensile strength of compacts formed from them.