bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of pH, calcium and chloride ions on the binding of tolmetin to human serum albumin: circular dichroic, dialysis and fluorometric measurements
Authors: Matsuyama Kenji , Sen Asok C , Perrin John H 
Published: April 2011

Abstract
The binding of the non-steroidal anti-inflammatory drug, tolmetin (1-methyl-5-p-toluoylpyrrole-2-acetic acid) to human serum albumin (HSA) has been shown by circular dichroism, fluorescence and equilibrium dialysis to be dependent on the N-B conformational change of the albumin. The influence of calcium and chloride ions on the interaction was also investigated using the same techniques. Experiments suggested that calcium ions increased the binding constant of tolmetin to HSA whereas chloride ions decreased it. The displacement study showed that tolmetin caused a significant increase in the affinity of diazepam to HSA whereas it decreased the binding of warfarin to HSA. Tolmetin seems to cause an allosteric change in the diazepam binding site in spite of it sharing a primary site with warfarin.
Comparison of changes in locomotor activity with striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations following the bilateral intranigral injection of dopamine agonist drugs in rats
Authors: Kelly Eamonn , Jenner Peter , Marsden C David 
Published: April 2011

Abstract
Bilateral injection of apomorphine (2.5 μg) into the substantia nigra zona reticulata of rats reduced both locomotor activity and striatal HVA and DOPAC concentrations. Bilateral injection of dopamine (10 μg) did not affect locomotor activity whereas a higher dose of dopamine (50 μg) enhanced locomotor activity. Striatal HVA and DOPAC concentrations were unchanged following injection of dopamine. Bilateral injection of (±)-3PPP (0.1 or 2.5 μg) into the zona reticulata of the substantia nigra did not alter locomotor activity while a higher dose (10 μg) enhanced locomotion. Injection of (±)-3PPP (0.1–10 μg) into the zona reticulata was without effect on striatal HVA or DOPAC concentrations. The bilateral manipulation of nigral dopaminergic neurotransmission alters motor activity and nigrostriatal dopamine turnover in conscious rats. However, the changes in motor activity are not necessarily related to altered nigrostriatal activity, suggesting the involvement of dopamine receptors located at non-dopaminergic sites within the substantia nigra.
The effect of meptazinol on the guinea-pig sphincter of Oddi in-vitro
Authors: Wade V , Pleuvry B J , Modla C Y , Bradley P 
Published: April 2011

Abstract
Meptazinol causes a dose-dependent contraction of the guinea-pig sphincter of Oddi in-vitro. This was antagonized by atropine in concentrations which blocked the contractile response to acetylcholine but not that to KCl. Naloxone was unable to block the response of the tissue to meptazinol, and other opioid drugs had inconsistent effects. Although meptazinol has significant anticholinesterase activity on this preparation, comparison with neostigmine suggests that this is irrelevant to its contractile action.
Detrimental effect of propylene glycol on natural killer cell and neutrophil function
Authors: Denning David W , Webster A David B 
Published: April 2011

Abstract
Propylene glycol (PG) in a concentration of 0.5–1.0% inhibits natural cytotoxicity and neutrophil chemiluminescence. This is the first reported effect of PG on defence mechanisms in man. PG is frequently used as a vehicle in high concentrations by the pharmaceutical industry and it would be wise to consider its potential immunosuppressive effects in the evaluation of drug formulations.
Correlation between n-octanol/water partition coefficient and liquid chromatographic retention for caffeine and its metabolites, and some structure-pharmacokinetic considerations
Authors: Gaspari F , Bonati M 
Published: April 2011

Abstract
A method to establish the correlation between the reverse phase high performance liquid chromatographic retention of caffeine and its metabolites and their n-octanol/water partition coefficients is described. The log (P) values were always below zero, ranging from −0.02 to −2.03. The capacity factor quadratically back-extrapolated to 100% water eluent (k'w) was used as the index of lipophilicity. The compounds examined gave a good correlation (r &gt; 0.99) with log (k'w) if considered in separate series, depending on the substituent position. For a structure-pharmacokinetic relationship study, correlations were found between the partition coefficient and some pharmacokinetic parameters, suggesting that for drugs that are widely metabolized, any predictions of their disposition from physicochemical characteristics are hazardous.
Albumin microspheres for intra-articular drug delivery: investigation of their retention in normal and arthritic knee joints of rabbits
Authors: Ratcliffe J H , Hunneyball I M , Wilson C G , Smith A , Davis S S 
Published: April 2011

Abstract
The retention of 131I-labelled albumin microspheres and microsphere-entrapped [131I]rose bengal was investigated in normal and experimentally arthritic knee joints of rabbits. Albumin microspheres were cleared slowly from the joint cavity and no significant difference was observed between normal and inflamed joints. Entrapment of rose bengal within albumin microspheres was found to delay the clearance of the drug from the joint when compared with a solution of rose bengal. In addition, the retention time for entrapped rose bengal was dependent on the degree of inflammation present.
Central muscarinic activation elicits compulsive drinking behaviour in the rat
Authors: Schiavone A , Prudentino A , Giachetti A 
Published: April 2011

Abstract
Injection of bethanechol into the lateral cerebral ventricle of the rat induces a marked increase in drinking, within 30 min from administration. The response is dose-related, maximal water intake (6.1 ± 0.55 mL; mean ± s.e.) occurring at 10 μg of bethanechol. Peripheral administration of the agonist (up to 3 mg kg−1 i.p.) fails to elicit drinking. Among several specific antagonists only anti-muscarinic drugs produced a significant inhibition of the response, suggesting that the compulsive drinking behaviour in the rat is caused by activation of central muscarinic receptors. The drinking behaviour emerges as a reliable test to assess central muscarinic activity of both agonists and antagonists.
1-(ℴo-Methoxyphenyl)piperazine is a metabolite of drugs bearing a methoxyphenylpiperazine side-chain
Authors: Benfenati E , Caccia S , Vedova F Della 
Published: April 2011

Abstract
Drugs bearing an o-methoxyphenylpiperazine (oOCH3PP) moiety in the side-chain of their molecule may form oOCH3PP during biotransformation in-vivo in the rat. This has been verified by combined gas chromatography-mass spectrometry of urine from rats given orally a series of relatively new o-methoxyphenylpiperazine-substituted derivatives. The metabolite is reported to be biochemically and pharmacologically active and therefore its formation may have pharmacological significance, at least for derivatives undergoing extensive cleavage of the arylpiperazine side-chain.
Plasma protein binding—lipophilicity relationships: interspecies comparison of some organic acids
Authors: LÁZNÍČEK M , KVĚTINA J , MAZÁK J , KRCH V 
Published: April 2011

Abstract
Relationships between plasma protein binding of 11 organic acids (benzoic and phenylacetic acid derivatives) and their lipophilicity were studied in man, rabbits, rats and mice. For description, the relationship fu = 1/(1 + aDb) was developed, where fu is the fraction of the unbound drug in plasma, D is the partition coefficient octanol/water and a and b are parameters. While the value of the parameter a is widely different in interspecies comparison, the value of the parameter b is very close in all species studied and is approximately equal to 1. The model used allows the simple calculation of the extent of plasma binding of structurally similar drugs from their lipophilicity, or conversion of the extent of plasma binding from one species to another.
Fate of haem after parenteral administration of haem arginate to rabbits
Authors: LINDÉN I-B , TOKOLA O , KARLSSON M , TENHUNEN R 
Published: April 2011

Abstract
Rabbits were injected either intravenously or intramuscularly with [14C]haem arginate and [59Fe]haem arginate (haem 5 mg kg−1). The main part (80%) of AUCINF of labelled haem was associated with the β-phase, T½ being about 6 h. Only 1% of the haem dose had been taken up by the red blood cells. In contrast, the iron moiety from the haem molecule was effectively utilized. Thirty days post-injection of [59Fe]haem arginate, 40% of the dose after intravenous injection and 60% after intramuscular injection was circulating with the red cells. Radioactivity was shown to concentrate in the liver, where haem is mainly metabolized and eliminated. An accumulation of haem in the adrenals was also evident. Haem itself did not concentrate in the bone marrow, and a negligible amount of radioactivity was recovered from brain, implying a poor penetration of the blood brain barrier.
Adrenergic receptor subtype activation by (+)-, (−)- and (±)-norephedrine in the pithed rat
Authors: MOYA-HUFF FERNANDO A , MAHER TIMOTHY J 
Published: April 2011

Abstract
The ability of (±)-norephedrine (phenylpropanolamine) and its component isomers, (+)- and (-)-norephedrine, to activate adrenergic receptor subtypes in the cardiovascular system of the urethane/chloralose-anaesthetized pithed rat has been investigated. At all adrenoceptor subtypes, (-)-norephedrine was the most potent agonist followed by (±)- then (+)-norephedrine. The greatest activity was observed at the α1-receptor, with little activity observed at either β1 or β2-adrenoceptors. Reserpinization shifted the (-)- norephedrine dose-response curve slighty to the right, indicating that only a minor portion of its activity is due to the release of stored endogenous catecholamines. These results suggest that most of the cardiovascular activity of the compounds is through the direct activation of α1-adrenoceptors.
Evaluation of permeability enhancement of hydrophilic compounds and macromolecular compounds by bile salts through rabbit corneas in-vitro
Authors: Morimoto Kazuhiro , Nakai Tohru , Morisaka Katsuaki 
Published: April 2011

Abstract
The effect of bile salts, sodium taurocholate (TC-Na) and sodium taurodeoxycholate (TDC-Na), on the permeability of hydrophilic compounds and macromolecular compounds through the rabbit cornea in-vitro was examined. 6-Carboxyfluorescein and glutathione were used as low molecular weight hydrophilic model compounds and FITC-dextran (mol. wt 4000) and insulin were used as relatively macromolecular model compounds. TC-Na (2 and 10 mM) marginally increased the corneal permeabilities to hydrophilic compounds and macromolecular compounds. TDC-Na (2 and 10 mM) markedly increased the corneal permeabilities of these compounds.
The effect of phenylpentenyl-khatamines on the release of radioactivity from rat striatal tissue prelabelled with [3H]dopamine
Authors: Kalix P , Geisshüsler S , Brenneisen R 
Published: April 2011

Abstract
The CNS-stimulating properties of leaves of the khat shrub (Catha edulis, Celastraceae) are presumed to be due mainly to (-)-cathinone, a phenylpropylamine alkaloid that has been shown to have an amphetamine-like releasing effect at physiological catecholamine storage sites. Recently, several phenylpentenylamine alkaloids have been identified in khat leaves, and these have been evaluated, in-vitro, in the present study for their ability to induce release of radioactivity from [3H]dopamine-prelabelled rat striatal tissue. It was found that the phenylpentenylamines have a weak releasing effect, and are therefore considered unlikely to play an important role in the stimulating properties of khat leaves.
Effect of lapachol, a naphthaquinone isolated from Tectona grandis, on experimental peptic ulcer and gastric secretion
Authors: Goel R K , Pathak N K R , Biswas M , Pandey V B , Sanyal A K 
Published: April 2011

Abstract
Lapachol, a naphthaquinone isolated from the roots of Tectona grandis given at a dose of 5 mg kg−1 p.o. twice daily for 3 days was found to have an anti-ulcerogenic effect on subsequently induced experimental gastric and duodenal ulcers in rats and guinea-pigs. Its action appears to be associated with an effect on the protein content of gastric juice, and it reversed aspirin-induced changes in peptic activity, protein and sialic acid.
The anticoagulant activity of some selected warfarin analogues
Authors: Obaseki Andrew O , Coker Herbert B 
Published: April 2011

Abstract
The anticoagulant activities of 6-, 7-, 8-, 4′-hydroxy, 6-chloro- and 6-bromowarfarin were determined in rabbits after intraperitoneal administration of 16.2 μmol kg−1 over 96 h. Substitution on the 4-hydroxycoumarin moiety resulted in reduction of the anticoagulant activity. 6-Chlorowarfarin was more potent than 6-bromowarfarin suggesting that the molecular size of 4-hydroxycoumarin moiety may be crucial for biological activity.
The effect of particle size and concentration on the adhesive characteristics of a model drug-carrier interactive system
Authors: Kulvanich Poj , Stewart P J 
Published: April 2011

Abstract
The effect of concentration and particle size on the adhesive tendency of drug particles in a model interactive system was investigated using a centrifuge technique. The model interactive system consisted of drug powders adhered to coated glass carrier beads. Adhesion profiles of per cent of drug remaining on the carrier versus the square of the speed of rotation were a logarithmic normal function. Increase in the adherent particle size and concentration decreased the adhesive tendency of all drug powders studied. Particle collisions during detachment and the formation of multiparticulate layers even before the monolayer saturation of the carrier surface were responsible for the reduced adhesive stability of the drugs on the carrier as the particle loading increased.
Experimental investigation of adhesion between powders and surfaces
Authors: Booth S W , Newton J M 
Published: April 2011

Abstract
The adhesion between two pharmaceutical powders (poly (ethylene glycol) 4000 and Sta-Rx 1500) and various metal and polymer substrates has been investigated. The powders were either deposited on the substrates with negligible force or forced on by spinning in a centrifuge. The force required to remove the particles was then evaluated by spinning the substrate-powder samples in a centrifuge and counting the remaining powder after rotation at various spéeds. The median adhesive force between the powders and various substrates was similar in the case of particles deposited with negligible force, with the exception of adhesion to PTFE, which was about one-third of the force. After the powders had been forced on to the substrate surface the median adhesive force increased. This increase was approximately five-fold for the Sta-Rx 1500 and up to thirty-fold for the PEG 4000. Differences in the adhesion between each powder and the various substrates were now evident with, for example, Sta-Rx 1500 adhering to stainless steel with a force of 1510 times 10−9 N, but to Dural with a force of 2380 times 10−9 N.
Antimicrobial activity of n-alkyltrimethylammonium bromides: influence of specific growth rate and nutrient limitation
Authors: Wright Naomi E , Gilbert Peter 
Published: April 2011

Abstract
The antimicrobial activity of an homologous series of n-alkyltrimethylammonium bromides has been assessed towards Escherichia coli grown at a variety of specific growth rates and under various conditions of nutrient limitation. For each individual set of growth conditions activity was parabolically related to the n-alkyl chain length of the compounds and thus to compound lipophilicity (log P). The compound that showed optimal activity and thereby optimal lipophilicity (log P***o) changed according to growth rate and nutrient limitation. Such changes are related to variations in the gross cell envelope composition of the cultures (phospholipid, lipopolysaccharide, neutral lipids, proteins). The data therefore support the hypothesis that changes in growth rate and nutrient limitation alter the overall lipophilicity of the cell envelope and thereby the optimal value of log P for compounds to traverse it. Additionally, the data suggest that for the compounds examined, the acidic: neutral phospholipid ratios of the cell envelope, also influence the permeation of it.
Cardiovascular responses in rats with chronic renal failure
Authors: Yates M S , Askey Elizabeth A , Bowmer C J 
Published: April 2011

Abstract
Cardiovascular responses were determined in rats with chronic renal failure (CRF) produced by five sixths nephrectomy and in sham-operated rats. The conscious systolic blood pressure of rats with CRF was significantly higher than the pressure in controls although, after anaesthesia, there were no significant differences in the mean arterial pressure between the two groups of rats. The pressor responses to noradrenaline in rats with CRF were not significantly different from those recorded in sham-operated controls. The bradycardia elicited by electrical stimulation of the vagus nerve was significantly diminished in rats with CRF. However, indomethacin treatment (1 mg kg−1 s.c. twice daily for 2 days) abolished the differences in response to vagal stimulation. Changes in heart rate in response to electrical stimulation of the cervical sympathetic nerve and to bolus i.v. injections of isoprenaline and carbachol were similar in rats with CRF and controls. The most notable disturbance of cardiovascular function in rats with CRF is the diminished cardiac chronotropic response to vagal stimulation which appears to be mediated by a presynaptic action of prostaglandins.
Comparison of the effects of nabumetone with indomethacin on rat gastric mucosal 6-keto-PGF1α production and on bile salt-induced changes in gastric mucosal function
Authors: Melarange R , Rashbrook L C 
Published: April 2011

Abstract
The effect of nabumetone on rat gastric mucosal cyclooxygenase activity ex-vivo and in-vitro has been compared with that of indomethacin. Nabumetone was less potent and less active in inhibiting the production of gastric mucosal 6-keto-PGF1α compared with indomethacin either ex-vivo or in-vitro. Anti-inflammatory doses of nabumetone failed to enhance bile salt-induced gastric erosion or mucosal permeability to dextran whereas indomethacin significantly enhanced gastric erosion and increased dextran permeability. These results suggest that nabumetone fails to promote gastric damage or increase permeability because of minimal effects on gastric mucosal cyclooxygenase.
Hypothermic effect of GABA in conscious stressed rats: its modification by cholinergic agonists and antagonists
Authors: Miñano F J , Sancibrian M , Serrano J S 
Published: April 2011

Abstract
γ-Aminobutyric acid (GABA) intraperitoneally injected (i.p.) produced a dose-dependent hypothermia in restrained rats. GABA-induced hypothermia (1000 mg kg−1) was antagonized by pretreatment with atropine (2&#x006d;̇5 and 10 mg kg−1 i.p.), hyoscine butylbromide (2&#x006d;̇5 mg kg−1 i.p.), hexamethonium (0&#x006d;̇75 mg kg−1 i.p.) or physostigmine (0&#x006d;̇2 mg kg−1 s.c). Hexamethonium (7&#x006d;̇5 mg kg−1 i.p.) did not influence the hypothermia induced by GABA. The antagonism by physostigmine of GABA-induced hypothermia was attenuated by pretreatment of the rats with either α-methyl-p-tyrosine (200 mg kg−1 i.p.) or hexamethonium (0&#x006d;̇7mg kg−1 i.p.), but it was potentiated by either atropine (5 mg kg−1 i.p.) or hexamethonium (0&#x006d;̇75 mg kg−1 i.p.). The data indicate that GABA-induced hypothermia may be partly mediated by acetylcholine release. Muscarinic receptors may play an important role in the effect of GABA. The results support the hypothesis of nicotinic presynaptic receptors modulating noradrenergic nerve endings that play a part in the hypothermic response of GABA.
An HPLC assay procedure of sensitivity and stability for measurement of acetylcholine and choline in neuronal tissue
Authors: Barnes N M , Costall B , Fell A F , Naylor R J 
Published: April 2011

Abstract
A method is presented for the sensitive and specific determination of acetylcholine and choline in neuronal tissue. The method is based on the separation of acetylcholine and choline by reversed-phase HPLC, passing the eluent into a post-column reactor containing choline oxidase and acetylcholinesterase covalently bound to vinyl sulphone bonded onto a hydroxyethyl methacrylate support, and electrochemical detection of the hydrogen peroxide formed. The limit of detection of the procedure is 1 pmol for acetylcholine and 500 fmol for choline. The excellent baseline stability of the method ensures the rapid and reliable processing of a large number of samples.
The effect of blending time on particle adhesion in a model interactive system
Authors: Kulvanich Poj , Stewart P J 
Published: April 2011

Abstract
The adhesive tendency of drug particles in a model drug carrier interactive system increased with blending time. The degree of interaction was measured using a centrifuge technique; the resultant adhesion profile of per cent retained on the carrier versus the square of the speed of rotation was a logarithmic normal function that allowed the determination of the S50 to characterize the adhesion tendency. The relative degree of adhesion of the drug particles in the interactive mixtures and the rate to attain adhesion saturation in the interactive system during the mixing process was markedly different for the three mixtures studied. The increased adhesive tendencies during blending were probably associated with triboelectrification of the drug and carrier particles.
Lack of inotropic selectivity of phosphodiesterase enzyme inhibitors in-vitro
Authors: Smith George W , Hall Janet C , West Philip A 
Published: April 2011

Abstract
Phosphodiesterase enzyme (PDE) inhibitors form a diverse category of chemical structures which display positive inotropic activity, but it is unclear as to how force/rate selective these are on the heart. In this study several recently developed PDE inhibitors, almost all of which are selective for the cardiac PDE III isoenzyme, were compared with the xanthine PDE inhibitor IBMX and with ouabain and the direct and indirect adenylate cyclase activators, forskolin and isoprenaline, respectively. These compounds were active in increasing paced guinea-pig left atrial force, the order of potency being: isoprenaline &gt; ouabain &gt; forskolin &gt; pimobendan &gt; IBMX &gt; sulmazole &gt; buquineran &gt; carbazeran &gt; milrinone &gt; piroximone &gt; amrinone. Ro 13-6438 and enoximone were however, both inactive. With the exception of buquineran and carbazeran, which produced bradycardia and were therefore force specific, all of the recently discovered PDE inhibitors increased the rate of contraction of the right atria and they were rate selective to the same extent as IBMX, isoprenaline and forskolin. Sulmazole, the only force selective PDE inhibitor of the compounds studied, was intermediate between IBMX and ouabain in force/rate selectivity and pimobendan showed no selectivity. Since both these agents also possess other actions, then these results suggest that in general, PDE III inhibitors do not show advantageous force selectivity in guinea-pig atria.
Coprecipitation of Enzymes with Water Soluble Starch—An Alternative to Freeze-drying
Authors: Randén Lennart , Nilson Jerker , Edman Peter 
Published: April 2011

Abstract
Krill proteases were prepared in solid form from a partially purified extract by coprecipitation of the enzymes with water-soluble starch in an organic solvent at 22°C. The precipitation did not affect the activity of the enzymes. The recovery of proteolytic activity was 100%. The thermostability of the krill proteases increased when incorporated in the starch precipitate. No reduction in enzymatic activity could be seen after storage at +50°C for 99 days. After milling the coprecipitate could be dispensed. The enzyme preparation consisted of irregular needle-shaped particles. This simple precipitation technique offers an alternative to freeze-drying or spray-drying.