bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of iontophoresis and vehicle pH on the in-vitro permeation of lignocaine through human stratum corneum
Authors: Siddiqui Ovais , Roberts Michael S , Polack Alan E 
Published: April 2011

Abstract
The effect of iontophoresis and the pH of aqueous vehicles on the rate and extent of permeation of lignocaine through excised human stratum corneum was investigated. In the absence of iontophoresis, the rate of penetration was greatest at the higher pH values where lignocaine exists mainly in the unionized form; iontophoresis was most effective at the lower pH values where lignocaine is mainly ionized. At pH 3.4 and 5.2, the flux increased during iontophoresis, by approximately 8.5 and 4 times, respectively, relative to that occurring without iontophoresis. The present results suggest that some weak electrolytes which show poor percutaneous penetration may be administered topically using iontophoresis provided the drug is kept in a highly ionized form.
Cytoprotective action of carbenoxolone sodium on ethanol-induced gastric lesions in rats and its inhibition by indomethacin
Authors: Wan B Y C , Gottfried The Late S 
Published: April 2011

Abstract
Carbenoxolone produced a marked and dose-related inhibition of ethanol-induced gastric lesions in rats. This cytoprotective action was inhibited progressively and significantly by increasing doses of indomethacin. The evidence presented confirms previous suggestions that prostaglandin(s) are involved in the cytoprotective action of carbenoxolone.
Effect of non-ionic surfactants in a polyacrylic acid gel base on the rectal absorption of [Asu1,7]-eel calcitonin in rats
Authors: Morimoto Kazuhiro , Akatsuchi Hiroaki , Morisaka Katsuaki , Kamada Akira 
Published: April 2011

Abstract
The effect of non-ionic surfactants in a polyacrylic acid gel base on the rectal absorption of [Asu1,7]-eel calcitonin, a calcitonin analogue, was studied in rats. Absorption was enhanced by a microenema which used a polyacrylic acid gel base, but it was reduced by the incorporation of polysorbate 80 (0.1-5% v/v). The incorporation of polyoxyethylene 9 lauryl ether (0.1-5% v/v) in the polyacrylic acid gel base enhanced the absorption. Rectal administration in the base containing 0.5% v/v polyoxyethylene 9 lauryl ether required a dose of the calcitonin 2-3 times greater than an intramuscularly administered dose to achieve an equivalent hypocalcaemic effect.
Assessment of bioavailability of experimental single-unit sustained release tablets of verapamil hydrochloride using the stable isotope technique
Authors: Marvola Martti , Kannikoski Anneli , Taskinen Jyrki , Ottoila Pekka 
Published: April 2011

Abstract
A stable isotope technique has been used to assess the bioavailability of sustained release verapamil products. The test formulations were tablets with a core containing 90 mg of verapamil hydrochloride coated with ethylcellulose film, the permeability of which was controlled using different amounts of hydroxypropyl methylcellulose. A product containing ethylcellulose 75% hydroxypropyl methylcellulose 25% w/w gave a single-unit sustained release tablet of verapamil hydrochloride that allowed a dose interval of 24 h. There was no loss in bioavailability, even though verapamil had extensive first-pass metabolism.
Physicochemical characterization of the human nail: solvent effects on the permeation of homologous alcohols
Authors: Walters Kenneth A , Flynn Gordon L , Marvel John R 
Published: April 2011

Abstract
To assess how vehicles might influence permeation through human nail, the diffusion of homologous alcohols (methanol to decanol) administered as neat liquids through finger nail plate has been studied using in-vitro diffusion cell methods and compared with permeation data for the same compounds in aqueous media. Permeation rates of the homologous alcohols through lipid depleted nail plate have also been assessed and the influences of dimethylsulphoxide (DMSO) and isopropyl alcohol on permeation rates of methanol and hexanol have been examined. With the exception of methanol, permeability coefficients are uniformly about five-fold smaller when the alcohols are undiluted than when they are applied in water. Overall parallelism in the permeability profiles under these separate circumstances of application is an indication that the external concentrations of the alcohols themselves are a determinant of their permeation velocities through the nail plate matrix. The even separation of the profiles suggests a facilitating role of water within the nail matrix. Chloroform/methanol delipidization of the nail led to increased penetration rates of water, methanol, ethanol and butanol. On the other hand, it caused a six-fold decrease in the permeation rate of decanol. Application of methanol and hexanol in DMSO somewhat retards their rates of permeation. Isopropyl alcohol also slows the permeation rate of hexanol but has little influence on that of methanol. Thus it appears that solvents which tend to promote diffusion through the skin horny layer have little promise as accelerants of nail plate permeability.
The influence of native porcine gastric mucus gel on hydrogen ion diffusion: the effect of potentially ulcerogenic agents
Authors: Turner N C , Martin G P , Marriott C 
Published: April 2011

Abstract
Experiments were carried out to investigate the ability of native gastric mucus gels to retard hydrogen ion diffusion. Mucus held between two polycarbonate membrane filters in a diffusion cell, separating equimolar solutions of NaCl and HCl, significantly reduced the rate of hydrogen ion diffusion and increased the time for the mean hydrogen ion front to traverse the mucus compartment (lag time) when compared to an unstirred layer of saline (P &lt;0.01). N-Acetylcysteine, sodium taurodeoxycholate and acetylsalicylic acid significantly increased the diffusion rate (P &lt;0.025); the lag time was significantly reduced by N-acetylcysteine (P &lt;0.001). In addition mucus gels were found to have buffering capacity at a pH &gt; 2. These observations suggest that native gastric mucus gels can retard hydrogen ion diffusion and that this retardation of diffusion is reduced by agents which are potentially damaging to the gastric mucosa.
Detection of host-derived contaminants in products of recombinant DNA technology in E. coli: a comparison of silver-staining and immunoblotting
Authors: Gooding R P , Bristow A F 
Published: April 2011

Abstract
Contamination of medicines produced in E. coli by recombinant DNA methodology with host-cell proteins is considered a potential problem with this type of method. In this report techniques for the detection of trace quantities of host-cell proteins in SDS-gel electrophoretograms were examined. Detection of E. coli proteins by immunoblotting, using antisera raised in rabbits to lysates of E. coli, was compared with detection using the ultrasensitive silver stain. Silver staining detected a larger number of E. coli proteins in a one-dimensional electrophoresis system than did immunoblotting. Proteins that were markedly antigenic in the rabbit were detected at a greater sensitivity by the immunoblotting approach. Both techniques detected contaminant proteins in a preparation of methionyl human growth hormone produced in E. coli known to be contaminated with host-cell proteins. No contaminating proteins were seen by either technique in more rigorously purified preparations of growth hormone. A combination of these two approaches would provide useful evidence of purity of medicines produced by recombinant DNA technology, and is potentially applicable to a wide range of host-vector systems.
Metabolite inhibition of nitroglycerin metabolism in sheep tissue homogenates
Authors: Cossum Paul A , Roberts Michael S 
Published: April 2011

Abstract
The metabolism of nitroglycerin in sheep tissue homogenates has been examined using tritiated nitroglycerin and a HPLC separation procedure. Nitroglycerin was metabolized by liver, lung, muscle, arterial and venous tissue to its dinitrometabolites and subsequently to mononitroglycerin. Addition of the dinitrometabolites substantially inhibited the degradation of nitroglycerin in all tissue homogenates.
Effect of bile acids on the binding of drugs and dyes to human albumin
Authors: Bowmer Christopher J , Donoghue Paul G , Leong Chee F , Yates Michael S 
Published: April 2011

Abstract
Chenodeoxycholic, cholic, deoxycholic and taurodeoxycholic acids were found to inhibit the binding of 2-(4′-hydroxybenzeneazo)benzoic acid, methyl orange, sulphadimethoxine and warfarin to human albumin. In addition, glycodeoxycholic acid inhibited the binding of sulphadimethoxine and warfarin. In contrast, these bile acids did not inhibit the binding of phenylbutazone. The extent of displacement was in the rank order of: dihydroxy acids (chenodeoxycholic and deoxycholic) &gt; trihydroxy acid (cholic) &gt; conjugates (glycodeoxycholic and taurodeoxycholic). Thus the introduction of polar groups into the steroid nucleus of bile acids reduces their effectiveness as binding inhibitors. Displacement was usually accompanied by a decrease in the apparent association constant which suggests that the mechanism of displacement may be competitive.
Absorption of exaprolol from the in-situ gastrointestinal tract of rats and dogs
Authors: Motheová O , Zemánek M , Faberova V , Trnovec T , Gabauer I , Styk J , Ďurišová M , Nosáľová V 
Published: April 2011

Abstract
The absorption rate of the β-adrenoceptor blocking drug, exaprolol, from the gastrointestinal tract was studied using in-situ methods in the rat and dog. Exaprolol was rapidly absorbed from the small and large intestine of rats and from the ileum of dogs. The cardiac output and regional blood flow decreased in rats to approximately one half of the original values within 30 min of the in-situ experiment. The logarithm of the amount vs time plots from dogs were linear, whereas with rats a curvilinearity appeared apparently because of the blood flow-limited absorption kinetics of this highly lipophilic drug. The data obtained suggest that exaprolol is suitable for administration in sustained release form.
Modification of the inotropic effect of digoxin by diazepam in rat left atria
Authors: Castillo-Ferrando J R , Perez-Ojeda E , Encina J L , Serrano J S 
Published: April 2011

Abstract
There is a pharmacokinetic interaction between digoxin and diazepam that increases the elimination half-life of digoxin. It may be due to a reduction of digoxin tissue concentrations and to an enhanced effect of diazepam on digoxin binding to plasma albumin. Diazepam (10−5 M) also induces a positive inotropic effect in guinea-pig isolated atria. In a study of a possible pharmacodynamic interaction between both drugs, the inotropic response to digoxin has been examined in rat isolated atria in the presence of diazepam. The atria were kept in Tyrode at 37 X, bubbled with 95% O2 and 5% CO2 and electrically stimulated at twice the threshold voltage. The results indicate that diazepam induces an inotropic effect at 10−5 M (P &lt;0.05) and reduces (P &lt;0.05) at 10−9, 10−7 and 10−5 M the inotropic response to digoxin (10−5 M).
Effect of β-funaltrexamine on opioid side-effects produced by morphine and U-50, 488H
Authors: Hayes A G , Skingle M , Tyers M B 
Published: April 2011

Abstract
Pretreatment of rats with the irreversible μ-opioid receptor antagonist, β-funaltrexamine (β-FNA), 20–40 mg kg−1 s.c., produced a dose-related antagonism of the reduction in respiratory rate, gastrointestinal (GI) propulsion, rotarod reaction latencies and body temperature produced by morphine administration 24 h later, suggesting that these effects are mediated via μ-opioid receptors. The k-receptor agonist, U-50,488H, was without effect on respiratory rate at the doses tested, but produced hypothermia, sedation and low maximum inhibition of GI propulsion. These effects of U-50, 488H were not blocked by β-FNA suggesting that they are mediated via k-receptors.
The pharmacological characterization of 3,4-dihydroxyphenylimino-2-imidazolidine (DPI) as a potent mixed α1/α2-adrenoceptor agonist rather than as a dopamine receptor agonist
Authors: van Oene J C , Horn A S 
Published: April 2011

Abstract
In the past decade many studies have been carried out on the pharmacological actions of the imidazoline derivative DPI (3,4-dihydroxyphenylimino-2-imidazolidine) because it has been proposed as a selective agonist at a postulated subtype of dopamine (DA) receptor. According to the first publication on this concept of multiple DA receptors, authored by Cools & van Rossum (1976), mammalian DA receptors can be divided into excitation-mediating (DAe) and inhibition-mediating (DAi) receptors. DAe receptors appeared to coincide with ‘classical’ DA receptors i.e. those that can be selectively stimulated with apomorphine and inhibited with haloperidol, whereas the newly postulated DAi receptors could be selectively stimulated with DPI and inhibited with ergometrine (Cools & van Rossum 1976, 1980). Though interesting from a conceptual point of view, the idea of the existence of DAi receptors in the mammalian brain was rather speculative, and Cools and coworkers consequently put much effort into attempting to provide it with an experimental basis. They found that in some test models DPI and ergometrine had indeed opposing effects, and they explained these results as being in strong support of the presence of DAi receptors and thus of the validity of the DAe/DAi concept (Cools et al 1976; Cools 1977). In spite of the latter conclusion, however, these authors have repeatedly revised their original concept, i.e. by the additional postulations of the ‘alpha-like norepinephrine receptor’ (Cools & van Rossum 1980) and of the ‘DAi/e receptor’ (Cools 1981).
The accumulation of an aryloxylkylamidine (501C) and 5-hydroxytryptamine in human polymorphonuclear leucocytes: a quantitative electron microscopy study
Authors: Read N G , Beesley J E , Blackett N M , Trist D G 
Published: April 2011

Abstract
The uptake of anilino -N-2-m-chlorophenoxypropylacetamidine (501C) and 5-hydroxytryptamine (5-HT), in human polymorphonuclear leucocytes (PMN) was investigated by quantitative ultrastructural autoradiography. The major concentration of both drugs was in the cytoplasmic granules, 71.5 ± 6.8% for [3 H] 501C, and 68.75 ± 6.1% for [3 H]5-HT. Lesser quantities of both drugs were associated with the nucleus; 18.1 ± 4.8% for [3 H] 501C and 23.0 ± 4.2% for [3 H] 5-HT. Only small amounts of activity were recorded at other sites. The data suggests that there may be common binding sites for 501C and 5-HT in PMN. Furthermore the concentration of 501C in PMN granules may also account for the damaging effect of high concentrations of the drug on PMN.
Acute blood pressure and urinary responses to single dose combinations of captopril and diuretics in conscious spontaneously hypertensive rats
Authors: Chiu P J S , Vemulapalli S , Barnett A 
Published: April 2011

Abstract
The present studies involved oral administration of captopril alone or in combination with individual diuretics in conscious, freely-moving spontaneously hypertensive rats (SHR). Both blood pressure (BP) and urinary fluid and electrolyte excretion were concomitantly measured. Captopril, 10 mg kg−1, caused a decrease in BP (-18 ± 3 mm Hg) which was not significantly different from control (-10 ± 2 mm Hg). Diuretics alone also failed to alter BP. However the BP-lowering effect of captopril was readily potentiated by concomitant administration of a single oral dose of frusemide (10 and 30 mg kg−1) in proportion to the magnitude of urinary loss. Hydrochlorothiazide at 1 and 3 mg kg−1 oral and metolazone at 0.3 and 1 mg kg−1 oral induced fluid loss similar to frusemide at 10 mg kg−1 and all produced comparable BP reduction in combination with captopril (25-32 mm Hg). Triamterene did not increase fluid excretion and was ineffective. In SHR with bilateral ureteral ligation, the synergistic effect of frusemide was abolished while that of hydrochlorothiazide still occurred with a delayed onset. It is concluded that concomitant measurement of BP and urinary excretion in conscious, freely-moving SHR is a useful technique for studying new antihypertensive drugs. Using this preparation it was found that enhancement of the acute hypotensive response to captopril with concomitant diuretic therapy occurs within 10 min and is primarily related to the fluid and Na loss, regardless of the diuretic agent used.
Identification of adrenoceptors and dopamine receptors mediating vascular responses in the superior mesenteric arterial bed of the rat
Authors: Nichols A J , Hiley C R 
Published: April 2011

Abstract
The nature of the adrenoceptors and dopamine receptors mediating vascular responses in the in-situ blood perfused superior mesenteric arterial bed of the rat have been studied. α1-Adrenoceptor agonists produced vasoconstriction but α2-agonists had no significant effect on vascular resistance. The vasoconstrictor effects of noradrenaline were antagonized by low doses of prazosin (26nmol kg−1 i.v.). Isoprenaline and salbutamol produced vasodilation when the vasculature was preconstricted with arginine vasopressin. The responses to isoprenaline were potently antagonized by propranolol (1.69 μmol kg−1 i.v.) and weakly but significantly reduced by practolol (3.75 μmol kg−1 i.v.) whereas the responses to salbutamol were unaffected by the same dose of practolol. After preconstriction of the vasculature and α-adrenoceptor blockade, dopamine and apomorphine produced dilator responses with both compounds producing the same maximal response and apomorphine being 1.8 times more potent than dopamine. The dopamine responses were present after the animals had been pithed and were resistant to spiperone (506 nmol kg−1 i.v.) but were antagonized by cis-α-flupenthixol (460 nmol kg−1 i.v.). These results suggest that this vascular bed possesses vasoconstrictor α1- but not α2-adrenoceptors, vasodilator β1 and β2-adrenoceptors and vasodilator dopamine receptors which appear similar to the D1-type found centrally.
Postjunctional effects of mianserin and its metabolites on the rat isolated anococcygeus muscle
Authors: Doggrell Sheila A 
Published: April 2011

Abstract
After rat isolated anococcygeus muscle had been treated with 6-hydroxydopamine to abolish noradrenergic transmission, the effects of mianserin and its metabolites alone on tone and on the contractile responses to methacholine and phenylephrine were studied. Mianserin (&gt; 3 times 10−5 M) and 8-hydroxymianserin (&gt; 3 times 10−6 M), but not desmethylmianserin and mianserin -N-oxide, induced contractions. The contractions to mianserin were not altered by phentolamine, atropine, cyproheptadine, ouabain and verapamil but were reduced in tissues treated with indomethacin. Thus the responses to mianserin may, in part, be mediated by the synthesis of prostaglandins. Mianserin (10−5 M) and 8-hydroxymianserin 10−7 −10−5 M) potentiated, mianserin- N-oxide had no effect, and desmethylmianserin (10−7 −10−5 M) inhibited methacholine-induced contractions. The inhibition of responses to phenylephrine was concentration-related with desmethylmianserin (10−7 −10−5 M) and mianserin- N-oxide (10−6 −10−5 M) but not with mianserin or 8-hydroxymianserin (10−7 −10−5 M). The effects of mianserin and its metabolites on responses to methacholine and phenylephrine were similar in the absence and presence of indomethacin. These results suggest that mianserin and 8-hydroxymianserin increase the tissue's sensitivity to methacholine by an action at the level, or distal to, the muscarine receptor. In addition to blocking α1-adrenoceptors, mianserin and 8-hydroxymianserin may have another postjunctional action at, or beyond, the α1adrenoceptor.
Phenolic analogues of reversed esters of pethidine
Authors: Casy A F , Ogungbamila F O 
Published: April 2011

Abstract
The preparation and stereochemical characterization of phenolic analogues of the reversed ester of pethidine, α-and β-prodine and a 1-phenethyl congener are described. All the compounds were weakly active or inactive as agonists in rodent antinociceptive tests and failed to antagonize fentanyl in rats. The results substantiate the view that the morphine and 4-phenylpiperidine groups of analgesics differ in their modes of interaction with opiate receptors, except possibly when the piperidine derivative carries a C-4 carbon substituent.
Enhancement of nasal absorption of insulin and calcitonin using polyacrylic acid gel
Authors: Morimoto Kazuhiro , Morisaka Katsuaki , Kamada Akira 
Published: April 2011

Abstract
The effects of polyacrylic acid gel on the nasal absorption of insulin and [Asusup&gt;1,7]-eel calcitonin were investigated in rats. The nasal administration of insulin (1 IU kgsup&gt;−1) in polyacrylic acid gel at 0.1 and 1% w/v showed maximum hypoglycaemic effects at 30 min and 1 h after administration, respectively. However, the nasal administration of insulin in carboxymethyl cellulose (1% w/v) solution had no hypoglycaemic effect at the same dose. When [Asu1.7]-eel calcitonin (10 U kg−1) was administered nasally in polyacrylic acid gel (0.1% w/v), a prominent hypocalcaemic effect was observed during the first 30 min. Nasal administration of [Asu1,7]-eel calcitonin in saline had no hypocalcaemic effect at the same dose. The results indicate that the polyacrylic acid gel base significantly enhanced the absorption of insulin and [Asu1,7]-eel calcitonin via the nasal cavity.
The effect of 6-oxo-prostaglandin E1 on human platelet aggregation in whole blood in-vitro
Authors: Wilsoncroft P S , Lofts F J , Griffiths R J , Moore P K 
Published: April 2011

Abstract
The effect of PGI2, 6-oxo-PGE1 and PGE1 on ADP-induced human platelet aggregation has been assessed in whole blood and in blood centrifuged to prepare plateletrich plasma (PRP). PG12 was the most potent antiaggregatory agent in both media. The concentration of PGI2 required to produce 50% inhibition of platelet aggregation was approximately 0.3 ng ml−1 in each case. In contrast both E series prostaglandins exhibited significantly greater (400-700%) anti-aggregatory activity when tested in whole blood than when tested in PRP. Since whole blood presumably represents a truer reflection of platelet reactivity in-vivo, we believe that the potency of 6-oxo-PGE1 (and PGE1) as inhibitors of platelet aggregation has been underestimated in previous experiments using PRP. In human whole blood 6-oxo-PGE1 has approximately 40% the anti-aggregatory activity of PGI2. The reasons for the increased anti-aggregatory potency of E series prostaglandins in whole blood is not known. We suggest that 6-oxo-PGE1 and PGE1 (but not PGI2) may prevent the release of pro-aggregatory ADP from red blood cells thereby enhancing their ability to inhibit platelet aggregation.
Distribution coefficients of atenolol and sotalol
Authors: Taylor P J , Cruickshank J M 
Published: April 2011

Abstract
Our original publication (Taylor & Cruickshank 1984) was addressed to one simple specific point: the confusion that has been caused by apparently contradictory data for the same two compounds. It is now criticised on two counts (Day & Parr 1984): that we used a confusing nomenclature; and that our treatment of the data was technically incorrect.
Force-displacement measurements in tableting
Authors: Ragnarsson Gert , Sjögren John 
Published: April 2011

Abstract
The influence of particle interaction, i.e. friction and bonding, on the net work (NETW) during compaction and on Heckel plots was tested by varying the particle size, the lubrication or the moisture content. The NETW was found to be significantly affected by particle interaction. The yield pressure, calculated from Heckel plots, was far less dependent on particle interaction and appears to be more useful for the evaluation of the deformation properties of materials. The NETW may be useful as a test of inter-lot variations in compaction behaviour of materials, due to its high sensitivity to both inter- and intraparticle properties, good reproducibility and low dependence upon die wall conditions. However, it appears to be a poor measure of the plastic properties of the substance.