bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of media and other variables on the BP solution rate test for slow lithium carbonate tablets
Authors: Wall B P , Parkin J E , Sunderland V B 
Published: April 2011

Abstract
The British Pharmacopoeial test for assessing the solution rate of slow lithium carbonate tablets has been evaluated using ‘controlled release’ tablets containing 400 mg of lithium carbonate. No significant differences in lithium release were found when the volume of media used in the test was reduced from 250 ml to 200 ml, the final stage of the test in pH 6.8 phosphate buffer reduced from 5 to 3 h, the number of tablets in each thimble reduced from three to one, or the prescribed phosphate buffers replaced with phthalate and Tris, respectively. A four-fold increased concentration of phosphate in the phosphate buffers used resulted in a significant retardation in lithium solution rate. This was not attributable to an ionic strength effect but possibly to the formation of trilithium phosphate at the interface. Dissolution studies using the USP Basket Method showed a significantly slower release rate of one tablet into 900 ml of phosphate buffer compared with Tris buffer. This difference was markedly increased when three tablets were investigated in 200 ml of similar media. These differences were considered to be due to the formation of the much less soluble trilithium phosphate in the phosphate buffers.
Polysorbate 20 as a drug release regulator in ethyl cellulose film coatings
Authors: Lindholm Tuula , Lindholm Bengt-Åke , Niskanen Mervi , Koskiniemi Jaakko 
Published: April 2011

Abstract
Tablet coatings of hydrophobic ethyl cellulose have been made more hydrophilic by the addition of a non-ionic surfactant, polysorbate (Tween) 20, to the film. As its content increased, so did the release of sodium salicylate from the coated tablets. With a certain content of surfactant and specific thickness of the tablet coat, zero order release kinetics were observed. Leaching of the polysorbate 20 occurred from all formulations. Scanning and transmission electron micrographs showed that the structure of the coats consisted of several layers parallel to the tablet surface. Polysorbate 20 was seen as small drops in some coats.
Effect of urapidil on rat brain catecholamine synthesis
Authors: Pugsley T A , Myers S 
Published: April 2011

Abstract
The effects of urapidil, a clinically effective antihypertensive drug, on the in-vivo rate of synthesis of rat brain noradrenaline (NA) and dopamine (DA) was determined. A significant dose-dependent increase in dopa concentration by urapidil after dopa decarboxylase inhibition by NSD 1015 was observed in brain stem (3–30 mg kg−1 i.p.) and striatum (10–30 mg kg−1 i.p.), indicating increased NA and DA turnover, respectively, most probably a result of central blockade of brainstem α1-adrenergic and striatal DA receptors. These results indicate that urapidil may possibly exert its central hypotensive action in part by a reduced influence on brain stem NA, thus reducing central sympathetic outflow.
Does naloxone induce relaxation of guinea-pig airway smooth muscle?
Authors: Soulioti A M A , Leonard M , Rodger I W 
Published: April 2011

Abstract
The effects of the opiate receptor antagonist naloxone were investigated on isolated preparations of guinea-pig trachealis contracted with either histamine, methacholine or KC1. The commercially available solution of naloxone (Narcan) induced concentration-dependent relaxation of the contracted airway preparations. In stark contrast, aqueous solutions of naloxone were without any significant relaxant effect. Aqueous solutions of the preservatives (methyl and propyl hydroxybenzoate) present in the vehicle used in the commercial formulation of naloxone mimicked exactly the relaxant effects induced by Narcan. Thus, naloxone does not directly induce relaxation of airway smooth muscle. The effects of Narcan can be solely attributed to the activity of the preservatives present in the vehicles. The mechanism underlying the bronchodilator activity of methyl and propyl hydroxybenzoate is unknown but is not related to receptor blockade or to alterations in the intracellular levels of cyclic AMP.
Compounds extracted from feverfew that have anti-secretory activity contain an α-methylene butyrolactone unit
Authors: Groenewegen W A , Knight D W , Heptinstall S 
Published: April 2011

Abstract
Extracts of feverfew inhibit secretion of granular contents from platelets and neutrophils and this may be relevant to the therapeutic value of feverfew in migraine and other conditions. In this investigation we fractionated an extract of feverfew and obtained eleven fractions with anti-secretory activity. The active fractions, together with two fractions that were devoid of anti-secretory activity, were examined using 1H NMR and infrared spectroscopy. All the active fractions (but neither of the inactive fractions) contained compounds with an α-methylene butyrolactone unit. Five compounds that contain this unit were identified as parthenolide, 3-β-hydroxyparthenolide, secotanapartholide A, canin and artecanin, all of which are sesquiterpene lactones. It is very likely that these and other sesquiterpene lactones that contain an α-methylene butyrolactone unit are responsible for the anti-secretory activity in extracts of feverfew.
Antipyrine kinetics following partial blood exchange with Fluosol-DA in the rat
Authors: Shrewsbury Robert P , White Sonja G , POLLACK Gary M , Wargin William A 
Published: April 2011

Abstract
The effects of partial blood exchange with Fluosol-DA on hepatic microsomal oxidative metabolism have been studied in the rat. Antipyrine clearance (Cl) was used as an in-vivo measure of the activity of the mixed function oxidase system. Rats were partially exchanged with Fluosol-DA and dosed with antipyrine at selected time intervals following exchange. No change in antipyrine Cl was observed at 0.5 h, but there was a statistically significant decrease at 24 h and then an increase by more than 50% relative to control at 48 and 72 h. These data indicate that the effects of Fluosol-DA on hepatic function are time-dependent and that Fluosol-DA has the potential both to inhibit and to enhance hepatic metabolism. The possibility of altered hepatic metabolism should be considered when patients transfused with Fluosol-DA are given drugs primarily metabolized by the mixed function oxidase system.
Calculated and actual changes in β-adrenoceptor number associated with increases in rat and guinea-pig cardiac sensitivity
Authors: Chess-Williams Russell G , Broadley Kenneth J , Sheridan Desmond J 
Published: April 2011

Abstract
Chronic catecholamine depletion induced by reserpine pretreatment of rats, or 6-hydroxydopamine pretreatment of guinea-pigs, resulted in an enhanced sensitivity of isolated papillary muscles to isoprenaline. This hypersensitivity was accompanied by l.41-(rats) and 1.52-fold (guinea-pigs) increases in the number of [3H]dihydroalprenolol binding sites, without changes in binding affinity. An equation was derived for calculation of increases in receptor number. Application of this showed that substantially greater increases in receptor number were required (2.32- to 4.04-fold) to account for the degree of supersensitivity observed.
On the binding of cinmetacin and indomethacin to human serum albumin
Authors: Montero M T , Pouplana R , García S , Valls O 
Published: April 2011

Abstract
The binding of two non-steroidal anti-inflammatory drugs, indomethacin and cinmetacin, to human serum albumin was studied by dynamic dialysis at 37 °C and pH 7.4. Cinmetacin is bound more than indomethacin. The affinity constant for the primary binding site is 4.28 × 106 M−1 for cinmetacin and 1.4 × 106 M−1 for indomethacin. The protein binding of indomethacin is decreased in the presence of cinmetacin.
Functional evidence for altered activity of gabaergic receptors following chronic desipramine treatment in rats
Authors: Borsini Franco , Giuliani Sandro , Meli Alberto 
Published: April 2011

Abstract
The antinociceptive effect of subcutaneous 4,5,6,7-tetrahydroisoxazol[5,4-c]pyridin-3-ol (THIP) or (±)-baclofen, measured as reaction time of rats placed on a plate heated to 55 °C, was assessed after a single or the last repeated (18 consecutive days) dose (5 mg kg−1 once daily) of subcutaneous desipramine. Baclofen (10 mg kg−1)-induced antinociception was reduced by acute and unaffected by chronic desipramine treatment. On the contrary, THIP (20 mg kg−1)-induced antinociception was unaffected by acute and reduced by chronic desipramine.
α-Adrenoceptor blocking activity of fenoldopam (SK&F 82526), a selective DA1 agonist
Authors: Nakamura Shigeru , Kohli Jai D , Rajfer Sol I 
Published: April 2011

Abstract
The α-adrenoceptor blocking activity of fenoldopam (SK&F 82526), a selective dopamine vascular receptor (DA1) agonist, was evaluated in isolated segmental preparations of rabbit aorta, dog mesenteric and rabbit splenic arteries. Fenoldopam, in concentrations ranging from 10−6 to 10−4 M, produced parallel, dextral shifts of concentration-contractile response curves to noradrenaline. Slopes of the Schild regression lines were not significantly different from unity in the three vessels. pA2 values for fenoldopam in the rabbit aorta, dog mesenteric and rabbit splenic arteries were 5.48 ± 0.08, 5.78 ± 0.05, and 5.20 ± 0.05, respectively. In experiments where the drug was added to the bathing medium before exposing the vascular segments to the irreversible α-adrenoceptor antagonist, phenoxybenzamine, fenoldopam provided nearly complete protection against α-adrenoceptor blockade. These results demonstrate that fenoldopam possesses α-adrenoceptor antagonist activity and competes with α-phenoxybenzamine, for occupancy at the same receptor site.
Effect of some centrally administered putative amino acid neurotransmitters on carrageenan-induced paw oedema in rats
Authors: Bhattacharya S K , Sarkar M K 
Published: April 2011

Abstract
The possible modulatory effect of central amino acid neurotransmitters on carrageenan-induced paw inflammation has been investigated in rats. Eight putative amino acid neurotransmitters were administered intracerebroventricularly and their effect on the peripheral inflammation was noted. The inhibitory amino acid transmitters, GABA, glycine and taurine attenuated the peripheral oedema, while the excitatory amino acid transmitters, glutamic acid and aspartic acid had a pro-inflammatory effect. However, the other putative amino acid neurotransmitters, proline and alanine (inhibitory) and cysteic acid (excitatory) did not affect carrageenan-induced oedema.
Lack of effect of omeprazole, a potent inhibitor of gastric (H++ K+) ATPase, on hepatic lysosomal integrity and enzyme activity
Authors: Grinpukel Susan , Sewell Richard , Yeomans Neville , Mihaly George , Smallwood Richard 
Published: April 2011

Abstract
The substituted benzimidazole, omeprazole, is a potent inhibitor of the ATP-dependent proton pump of the parietal cell. Since there is accumulating evidence that hepatic lysosomes also possess an ATP-dependent proton pump system to maintain internal acidification, and since antibodies to the putative lysosomal proton pump protein are immunologically similar to the parietal cell (H+ + K+) ATPase, we studied the effects in rats of six days of omeprazole treatment on hepatic lysosomal function. Omeprazole, 5 mg kg−1, a dose five times the ED50 for gastric acid secretion inhibition in rats, did not alter the activity of three representative lysosomal enzymes in liver (acid phosphatase, β-galactosidase and N-acetyl-β-glucosaminidase) nor did it alter lysosomal enzyme latency, a measure of the integrity of the lysosomal membrane. Furthermore, bile flow and the secretion of lysosomal enzymes into bile were also unaffected by omeprazole. These data indicate that in rats short-term treatment with omeprazole, in doses that markedly inhibit gastric acid secretion, has no major biological effect on liver lysosomal integrity and lysosomal enzyme activity.
Correlation between in-vitro microsomal enzyme activity and whole organ hepatic elimination kinetics: analysis with a dispersion model
Authors: Roberts Michael S , Rowland Malcolm 
Published: April 2011

Abstract
A new model, the dispersion model of hepatic elimination, is applied to the correlation between in-vitro microsomal data and corresponding rat isolated perfused liver data for a number of drugs reported in the literature, whose extraction ratio varies over the range of 0.01 to 0.995. The dispersion model described the data better than either the ‘well-stirred’ model or the ‘parallel-tube’ model, two other widely used models of hepatic elimination. The experimental data support the concept that elimination of solutes is affected by is a considerable dispersion on passage through the liver.
The prediction of compatibility/incompatibility in blends of ethyl cellulose with hydroxypropyl methylcellulose or hydroxypropyl cellulose using 2-dimensional solubility parameter maps
Authors: Rowe R C 
Published: April 2011

Abstract
Typical two dimensional solubility parameter maps for ethyl cellulose, hydroxypropyl methylcellulose and hydroxypropyl cellulose have been constructed using literature data. The maps of the polymers showed some degree of overlap indicating some mutual compatibility. Compatibility between ethyl cellulose and hydroxypropyl cellulose was greater than between ethyl cellulose and hydroxypropyl methylcellulose. The maps may also be used to predict the effect of added plasticizers.
Polyalkyl cyanoacrylate nanocapsules
Authors: el-Samaligy M S , Rohdewald P , Mahmoud H A 
Published: April 2011

Abstract
In-situ polymerized methyl cyanoacrylate (MCA), ethyl cyanoacrylate (ECA), and butyl cyanoacrylate (BCA) were used to prepare nanocapsules of fluorescein or doxorubicin as markers by a w/o emulsion interfacial polymerization technique. Different concentrations of MCA were also used to show the effect of monomer concentration. The nanocapsules were characterized by electron microscopy, particle size analysis, holding capacity and in-vitro release of the marker substances. After selection of the polymerization solvent system, nearly spherical nanocapsules were obtained using each of the monomers. Most of the nanocapsules prepared were in the particle size range 500–1500 nm diameter. They were able to hold 55–74% of the marker initially present in aqueous solution. In-vitro dissolution studies showed that release of marker was retarded variably in an increasing order from nanocapsules containing MCA, ECA then BCA. Increasing the concentration of the monomer in the nanocapsules led to retardation of marker release.
Effect of thermal history on the glassy state of indapamide
Authors: Serajuddin Abu T M , Rosoff Morton , Mufson Daniel 
Published: April 2011

Abstract
The effects of thermal history, e.g. cooling rate, annealing, etc., on the thermal behaviour of indapamide glass were determined by differential scanning calorimetry (DSC). The glass was prepared by heating indapamide crystals (m.p. 162 °C) to 180 °C., and then cooling the melt to room temperature. The glass transition temperature (Tg) of the material was 98 °C. An endotherm, due to thermal relaxation of the glass, was observed in the DSC thermogram when indapamide glass was prepared by slow cooling or was annealed isothermally at a temperature below Tg. Such enthalpy relaxation may be observed during ageing of pharmaceutical glasses and might influence their physicochemical properties.
Enhanced serum concentrations of Ara-C using suppositories containing tetrahydrouridine as a deamination inhibitor of Ara-C
Authors: Liversidge G G , Nishihata T , Engle K K , Higuchi T 
Published: April 2011

Abstract
Rectal bioavailability of Ara-C (serum AUC 4 h: 65 μg h−1 ml−1) administered in a suppository formulation containing tetrahydrouridine (a deamination inhibitor) and sodium salicylate (an adjuvant) to dogs was better than that from a suppository formulation without tetrahydrouridine (serum AUC 4 h: 18 μg h−1 ml−1).
Isoprenaline-induced changes in activity of the endogenous inhibitor of cAMP-dependent protein kinases under conditions of β-adrenoceptor supersensitivity
Authors: Zawilska J , Szmigielski A 
Published: April 2011

Abstract
Isoprenaline-induced changes in activity of an endogenous, specific inhibitor of cAMP-dependent protein kinases (type I inhibitor) under conditions of experimental supersensitivity of β-adrenoceptors were investigated in rat hippocampus and brain stem. Both subchronic administration of reserpine (2.5 mg kg−1, i.p., 4 days, once daily) and i.c.v injections of 6-hydroxydopamine (250 μg/ventricle, bilaterally, 48 h apart), which are known to increase β-adrenoceptor sensitivity in the rat brain, markedly enhanced the response of the type I inhibitor activity to isoprenaline. To obtain a significant decrease of type I inhibitor activity in the examined brain structures of these animals, doses of isoprenaline 2–5 times lower than in control groups had to be used. It is suggested that the isoprenaline-induced decrease of type I inhibitor activity might be used as an index of central β-adrenoceptor reactivity in-vivo.
The formation and characterization of hydrocortisone-loaded poly((±)-lactide) microspheres
Authors: Cavalier M , Benoit J P , THIES C 
Published: April 2011

Abstract
The solvent evaporation process has been used to form hydrocortisone-loaded microspheres from poly((±)-lactide) (PLA) and a lactide-glycolide copolymer (65/35). Methylene chloride was the casting solvent. Partially hydrolysed (88%) poly(vinyl alcohol) and methylcellulose were used as aqueous phase emulsifiers. Methylcellulose was preferred, because it gave stable emulsions as the amount of hydrocortisone being encapsulated increased whereas poly(vinyl alcohol) did not. With methylcellulose as the emulsifier, a broad size range of spherical microspheres containing up to 50% (w/w) hydrocortisone could be prepared. Thermal and X-ray analyses established that poly((±)-lactide) microspheres containing hydrocortisone retained thermal events characteristic of both materials. This is evidence that such microspheres contain, to some extent, crystalline hydrocortisone domains dispersed in a PLA matrix. But most of the encapsulated drug was molecularly dispersed in the PLA glass. The stability of hydrocortisone in microspheres was evaluated in different storage conditions: no degradation of drug was found. The release of hydrocortisone from 250–350 μm diameter microspheres into agitated 37°C water (nitrogen atmosphere) was determined by HPLC analysis. The microspheres evaluated had initial hydrocortisone payloads of 12 to 47% (w/w). The rate of drug release increased as the initial drug payload carried by the microspheres increased. The release data are not adequately described by zero order, first order, or square-root-of-time release kinetics. Drug release from microspheres that contain 12% (w/w) hydrocortisone approached a plateau value well below the amount of drug actually carried by the microspheres. This is particularly true for hydrocortisone encapsulated in lactide-glycolide polymer.
The role of lipid peroxidation in acute doxorubicin-induced cardiotoxicity as studied in rat isolated heart
Authors: Julicher R H M , Sterrenberg L , Bast A , Riksen R O W M , Koomen J M , Noordhoek J 
Published: April 2011

Abstract
Doxorubicin induces an acute cardiotoxicity that becomes manifest in isolated hearts as a deterioration in mechanical function. The oxidative component in this myocardial damage has been investigated. The effects of doxorubicin on the activity of superoxide dismutase and the capacity of the glutathione system, factors of the cellular protective mechanism against free radicals, were examined in rat isolated heart. Doxorubicin was found to reduce the capacity of the protective mechanisms. Whether oxidative membrane damage due to excessive free radical formation plays a role in the pathogenesis of the acute cardiotoxic action of doxorubicin was also examined. Its acute effect on myocardial contraction amplitude, frequency of beating, coronary flow and on the above mentioned biochemical parameters was compared in rat hearts sufficient or deficient in vitamin E. Peroxidation of lipids was measured as the formation of malondialdehyde, one of the final products of this process. Vitamin E deficiency neither aggravated the decrease in the capacity of the cellular protective factors nor worsened the reduction in myocardial function. Nor did induction of lipid peroxidation by doxorubicin occur in vitamin E-deficient hearts. It was concluded that lipid peroxidative damage most probably is not decisive in the development of the acute cardiomyopathy in rats.
Monoamine oxidase activities in dissociated cell fractions from rat skeletal muscle
Authors: Lyles Geoffrey A , Archer David R 
Published: April 2011

Abstract
Collagenase was used to dissociate rat skeletal muscle (gastrocnemius) into its constituent cells, from which a myocyte fraction enriched in striated muscle cells, and a non-myocyte fraction containing cells of connective tissue and vascular origin, were prepared. The activities of amine oxidase enzymes and alkaline phosphatase (AP) were then assayed in these fractions, and also in homogenates prepared from corresponding samples of non-dissociated tissue. The specific activities of the semicarbazide-sensitive amine oxidase (SSAO) and AP were considerably higher (30 to 35-fold) in non-myocyte than in myocyte fractions. AP is generally considered to be present predominantly in vascular cells of skeletal muscle, with little, if any, in skeletal muscle cells themselves. Thus, the results obtained may indicate a similar localization for SSAO activity. Support for this came from histochemical studies, which showed staining for SSAO primarily over the walls of larger blood vessels in the muscle. Unlike SSAO and AP, were marked differences in MAO-A activity between myocyte and non-myocyte fractions were not found, suggesting that MAO-A is more probably a constituent of cells within both fractions.
Pulmonary absorption of carboxyfluorescein in the rat
Authors: Woolfrey S G , Taylor G , Kellaway I W , Smith A 
Published: April 2011

Abstract
The pulmonary absorption of the fluorescent marker 6-carboxyfluorescein (CF) has been characterized. CF was administered intratracheally (i.t.) as a fluid instillate to pentobarbitone-anaesthetized rats at doses of 0.5 and 2 mg kg−1. The absorption was characterized by both model-independent and model-dependent pharmacokinetic analyses of blood concentration data with reference to previous intravenous (i.v.) studies. The mean fraction available (F) of CF was 90 and 112% with a mean absorption time of 107 and 109 min for the lower and higher doses, respectively. The terminal half-life for the i.t. administered CF (73 and 83 min for the 0.5 and 2 mg kg−1 doses, respectively) was significantly longer (P &lt; 0.001) than after i.v. dosing (18 min). This indicates a slow pulmonary absorption of CF. Blood concentration-time profiles could not be adequately described by models involving a simple first-order absorption process; a model incorporating two simultaneous first-order inputs gave a much better description, its absorption rate constants differing by almost two orders of magnitude.