bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of substitution in phenylacetic acids on their performance in the buccal absorption test
Authors: Beckett A H , Moffat A C 
Published: April 2011

Abstract
In the buccal test there is a linear relation between percentage absorption and alkyl chain length for a series of p-n-alkyl phenylacetic acids. Branching and cyclizing the alkyl chain reduces the percentage absorption. With the p-halogeno-acids, absorption increases as the atomic weight of the halogen atom increases; a chlorine atom is approximately equivalent to a methyl group in its effect on absorption. An oxygen atom between an alkyl group and ring is equivalent to reducing the chain length by one methylene group. The absorptions of α-methyl-substituted acids are greater than those of the unsubstituted acids.
Effect of organic matter and increased inoculum size on the minimum inhibitory concentration of crystal violet towards Staphylococcus aureus at various pH values
Authors: Adams E 
Published: April 2011

Abstract
The minimum inhibitory concentration towards Staphylococcus aureus of crystal violet at pH values 6, 7 and 8, increased when the inoculum size was increased or if egg albumen was added to the medium. When allowance was made for dye uptake, the minimum inhibitory concentration still exceeded that in the absence of organic matter. The increased minimum inhibitory concentration in the presence of muscle could in most cases be attributed to the removal of dye from solution.
The absorption, metabolism and elimination of (±)-N-(2-benzoyloxyethyl)norfenfluramine (JP992) in man
Authors: BECKETT A H , SHENOY E V B , BROOKES L G 
Published: April 2011

Abstract
The urinary excretion of N-(2-benzoyloxyethyl)norfenfluramine (JP 992) was examined in man with normal and acidic urine after oral administration of the drug; 86–100% of the dose was excreted in 48 h as metabolites of the drug having m-trifluoromethylbenzyl and benzoyl moieties, but no unchanged drug was detected. Norfenfluramine, N-2-hydroxyethylnorfenfluramine, and a metabolite, which on treatment with zinc and hydrochloric acid gave norfenfluramine, were excreted in urine. N-2-Hydroxyethylnorfenfluramine and a second unidentified metabolite were also excreted as both sulphate and glucuronide conjugates.
Homogeneity of pharmaceutical dispersed systems
Authors: Hersey J A , Cook P C 
Published: April 2011

Abstract
Pharmaceutical dispersions include an extremely important group of formulations for the administration of drugs. A consideration of the homogeneity or dose uniformity requirements of some pharmaceutical dispersions, including tablets, capsules, ointments, suspensions, lotions, emulsions and suppositories is given. Assessment of homogeneity, assuming possible required limits of dose conformity, enables a calculation of the particle size requirements. These may be limited by parameters other than homogeneity, for example, sedimentation in suspensions and physical stability of emulsions. The concept of homogeneity applied to these systems is useful for following the progress of powder mixing or other dispersion operations. It is also useful in examining the feasibility of achieving the desired degree of dispersion. Dose conformity could be an extremely important problem in some cases, where standards do not exist.
Butobarbitone metabolism in man: identification of 3î-ketobutobarbitone
Authors: Grove J , Toseland P A , Draffan G H , Clare R A , Williams Faith M 
Published: April 2011

Abstract
After single 200 mg oral doses of butobarbitone (I) in man, 5·4% was excreted in urine unchanged and 28·2% as the 3î-hydroxy metabolite (II) in six days. A new metabolite, the ketone (III), was detected in urine following oral administration both of I and of II. Oxidation of the hydroxy to the ketone metabolite was demonstrated in vitro with the 9000g fraction of rat liver. Use was made of selective ion monitoring g.c.-m.s. methods in metabolite detection.
A comparison of the effects of chronic administration of ethanol and acetaldehyde to mice: evidence for a role of acetaldehyde in ethanol dependence
Authors: Ortiz Aurelio , Griffiths Peter J , Littleton John M 
Published: April 2011

Abstract
After chronic exposure to ethanol or acetaldehyde vapour in concentrations which depress locomotor activity, mice show similar behavioural changes during withdrawal, and there is some degree of cross dependence. Mice exposed to acetaldehyde vapour had blood acetaldehyde concentrations similar to those of ethanol-treated mice, but brain acetaldehyde concentrations were apparently lower. There was no accumulation of acetaldehyde in blood or brain in either group during chronic administration. Chronic ethanol or acetaldehyde administration to mice is associated with an increase in the concentrations of the brain monoamines noradrenaline, dopamine and 5-HT. Withdrawal of ethanol or acetaldehyde is associated with a further, rapid, transient rise in the brain catecholamines, noradrenaline and dopamine. These results suggest that acetaldehyde may play a role in some of the biochemical and behavioural changes associated with ethanol dependence.
The granulation of binary mixtures: the effects of the composition of the granulating solution and the initial particle size of one component on granule properties
Authors: Opakunle W O , Spring M S 
Published: April 2011

Abstract
The effect of total solvent volume and the presence of dissolved material (other than binder) in the granulating solution, on the properties of granules prepared from lactose: boric acid mixtures has been studied. The total volume of binder solution available to powder mixtures during massing determines the ultimate average size of granules produced. Part-dissolution of powders being granulated contributes significantly to the average granule size by increasing the total solution volume and reducing the amount of powder to be wetted. Although the amount of PVP (binder) dissolved in the granulating solution contributed very little to granule size at the concentration examined, the combined effect of total volume of solution and amount of PVP present in the granulating solution determines granule strength and porosity. The effect of the initial particle size of lactose in a binary mixture with boric acid differs from its effect reported for single component systems.
A thin-layer chromatographic procedure for the assay of labelled noradrenaline and its metabolites in tissues and in incubation medium
Authors: Vohra M M , Jayasundar S 
Published: April 2011

Abstract
A method for the extraction, separation and quantitative determination of [3H]noradrenaline [3H-NA] and its five major metabolites has been devised using thin layer chromatography. This procedure was used to study the pattern of 3H-NA and its metabolites in the total radioactivity of the tissues and that released spontaneously from the rat isolated vas deferens. Whereas in tissues 3H-NA represented almost all of the total radioactivity (94·8 ± 0·47%), in the samples of spontaneous outflow it represented only 16·8 ± 2·1%. The rest was mostly accounted for by the five metabolites, primarily 3H-DOPEG and 3H-MOPEG. These findings show that in the rat vas deferens 3H-NA is preferentially metabolized via the two glycol derivatives, i.e. 3H-DOPEG and 3H-MOPEG.
The role of copper in preventing gastrointestinal damage by acidic anti-inflammatory drugs
Authors: Boyle E , Freeman P C , Goudie A C , Mangan F R , Thomson M 
Published: April 2011

Abstract
The ability of several non-steroidal acidic anti-inflammatory drugs to cause ulceration when given as copper complexes has been examined. The damage caused by clopirac, niflumic acid and aspirin was virtually abolished when they were given as copper complexes whereas the damage caused by indomethacin, ketoprofen and (+)-naproxen was unaltered. The lack of ulceration with three of these preparations appeared to be correlated with a much reduced ability to inhibit prostaglandin synthesis as determined using an in vitro enzyme system.
Anabolic and androgenic activities, in rat, of some nandrolone and androstanolone esters
Authors: Chaudry M A Q , James K C , Ng C T , Nicholls P J 
Published: April 2011

Abstract
The anabolic and androgenic activities of the formate to undecanoate esters of nandrolone and formate to valerate esters of androstanolone, after intramuscular injection, have been determined in rat. The response to a given dose was measured as cumulative weight (the area under the plot of weight of indicator organ against time). Levator anus muscle was used to assess anabolic activity, and the sum of the cumulative weights for prostate and seminal vesicles for androgenic activity. Log dose-log cumulative weight plots were parallel, and biological activities were expressed as the cumulative weight corresponding to a 2 μM dose, calculated from the regression lines. Anabolic-androgenic ratios for both series were calculated and were found to be minimum in the region of the propionate and butyrate. The anabolic-androgenic ratios of the nandrolone esters continued to increase after the minimum, as the series ascended. This method is believed to give a reliable assessment of anabolic and androngenic activities of steroid esters.
A sensitive biological assay for prostaglandin E and acetylcholine
Authors: Vapaatalo H , Lindén Inge-Britt , Parantainen J 
Published: April 2011

Abstract
Superfused hamster stomach strip has been used in the bioassay of prostaglandin E2 (PGE2) and acetylcholine. The preparation proved very stable and had no spontaneous movements. The sensitivity to PGE2 (and PGE1) was in the range of 10−9 gml−1 and to acetylcholine 10−12 g ml−1. After treatment with physostigmine the sensitivity to acetylcholine was 10−15 g ml−1. In acetylcholine determination the preparation is more sensitive than any other method.
Preliminary investigations of the metabolism and pharmacological activity of β-hydroxytryptamines in mammals
Authors: PlavšIč V , Iskrić S , Kveder S , Tućan-Foretić M , Wolf D , Gjuriš V , Supek Z 
Published: April 2011

Abstract
β-Hydroxytryptamine and β-hydroxy-5-hydroxytryptamine were incubated with rat liver slices and oxidative deamination was established as the main route of metabolism: in both instances the corresponding indole-3-glycollic acids and indole-3-ethane diols were the major metabolites. However, the rates of deamination of β-hydroxylated tryptamines, as measured manometrically, were found to be much slower than those of tryptamines non-hydroxylated in the side chain. The pharmacological activities of β-hydroxylated tryptamines were tested in guinea-pigs on resistance of respiratory pathways, spontaneous respiration, electrocardiogram, blood pressure and isolated ileum, using tryptamine and 5-HT as reference substances. The effects of tryptamines hydroxylated in the side chain were in general similar to those of corresponding tryptamines but of much lower intensities; only in increasing the blood pressure was β-hydroxytryptamine as active as tryptamine. The different reactions of these two groups of substances in the presence of some antagonists indicate that the receptors are probably not the same.
An in vitro method for the study of β-receptor mediated effects on slow contracting skeletal muscle
Authors: Waldeck Bertil 
Published: April 2011

Abstract
The soleus muscle of a guinea-pig was dissected out under pentobarbitone anaesthesia and mounted on a holder in an organ bath containing Krebs solution. The tendon was attached to a force transducer and subtetanic contractions were evoked by electrical field stimulation (0·5 ms pulses at 10·12 Hz for 1·5 or 3 s every 22 s). The experiments were performed at 37°. Terbutaline, a selective agonist at β2-adrenoceptors, reduced the force of subtetanic contractions in a dose-dependent manner, the EC50 being 0·2 μm. The reduction was due to a lessened degree of fusion. The results conform to previous in vivo studies.
Effects of paraffin coatings on the tensile strength of lactose
Authors: IRONO CECILIA I , PILPEL N 
Published: April 2011

Abstract
Measurements have been made of the tensile strength of lactose at different temperatures after coating it with up to 10−4 mol of various paraffin hydrocarbons g−1 of powder. Providing the coating is in a liquified form, either as a result of the ambient temperature or because of the localized high pressure at the points of true contact between the particles, there is a correlation between the tensile strength of the powder and the thickness and viscosity of the coating layer.
A stability-indicating assay for cefotaxime utilizing thin-layer chromatography with fluorescence detection
Authors: FABRE H , HUSSAM-EDDINE N 
Published: April 2011

Abstract
A t.l.c. method on silicagel plate with a fluorescence indicator has been carried out to increase the native fluorescence of cefotaxime and four of its degradation products. A simultaneous improved fluorimetric quantitation of the compounds in situ is proposed using a chromatogram spectrophotometer. The detectability (0.20 μg) shows that the procedure is twenty times more sensitive than high-pressure liquid chromatography with u.v. detection; it allows the determination of traces level (1%) degradation products.
Effect of the triazolobenzodiazepine estazolam on hepatic drug-metabolizing enzyme activity in rats
Authors: DOWN W H , HAWKINS D R , CHASSEAUD L F 
Published: April 2011

Abstract
Oral doses of the sedative/hypnotic estazolam (500 mg kg−1 day−1) to rats for 21 days caused statistically significant increases in liver weight, ascorbate excretion, cytochrome P-450 concentrations, and in aniline hydroxylase, ethylmorphine N-demethylase and glutathione S-transferase activities, as did approximately equivalent doses of flurazepam hydrochloride. Histologically, the centrilobular hepatocytes were enlarged. Some of these parameters were also increased after doses of estazolam of 100 mg kg−1 day−1, but not after 5 mg kg−1 day−1, which is about 50-fold greater than a clinical dose. Estazolam was a much less potent enzyme inducer than phenobarbitone under the conditions of these studies.
Stereospecific inhibition of oxotremorine-induced antinociception by (+)-isomers of opioid antagonists: comparison with opioid receptor agonists
Authors: BEN-SRETI M M , SEWELL R D E 
Published: April 2011

Abstract
The antagonistic effects of the two benzomorphan opioid antagonists, Mr-1452 and Mr-2266 and their respective (+)-isomers Mr-1453 and Mr-2267 upon morphine, ethylketocyclazocine (EKC), D-ala2-D-leu5–enkephalinamide (BW 180-C) and oxotremorine (OTMN) antinociceptive activity in mice were investigated. Pretreatment with either Mr-1452 (2.0 mg kg−1 i.p.) or Mr-2266 (2.0 mg kg−1 i.p.) significantly antagonized the antinociceptive effects of the three opioid agonists in the hot plate test, but were ineffective against OTMN, which in contrast was antagonized by the (+)-isomers. Interaction between the antagonists and submaximal analgesic doses of the opioids or OTMN produced similar results in the tail immersion assay. However, the effect of Mr-2267 on OTMN was biphasic and this contrasted with Mr-1453 which produced consistent and graded antagonism.
Release kinetics of sparingly soluble drugs from ethyl cellulose-walled microcapsules: salicylamide microcapsules
Authors: DONBROW M , BENITA S 
Published: April 2011

Abstract
Release rates of salicylamide from single-core ethyl cellulose (EC) coated microcapsules were measured as a function of wall thickness and core particle size. Whereas up to ca 50% release zero order kinetics were observed, the overall reaction fitted the first order and Higuchi matrix treatment. These were distinguished by the differential rate treatment, which showed that the overall release in fact followed the first order pattern. For investigating whether the process was membrane-controlled, the experimental rate constants were transformed into effective permeability constants (P0 and P1 with the aid of the microcapsule dimensional parameters needed in the relevant equations and compared with the salicylamide permeability constant for planar ethyl cellulose membranes (P), measured experimentally. P0 and P1 values obtained for a given microcapsule preparation were not identical: P0 was of the same order as P, P1 being much lower. While membrane-controlled release is evident, it is apparently accompanied by a first order concentration gradient change inside the microcapsule.
The effect on the rat isolated atria of amiodarone in the presence of either ouabain or verapamil
Authors: Bowles B J M , Pleuvry B J , Healy T E J 
Published: April 2011

Abstract
Amiodarone causes a decrease in the rate of contraction of the rat isolated atria and has a negative inotropic action in the paced preparation. Interactions occur between amiodarone and oubain and amiodarone and verapamil. It is possible that the clinically reported drug interaction with amiodarone may have a component of direct interactions on the myocardium rather than solely changes in plasma protein binding.
Studies of carbon-13 n.m.r. spectroscopy in pharmaceutical analysis: the composition of commercial samples of gentamicin sulphate
Authors: Kountourellis J , Parfitt R T , Casy A F 
Published: April 2011

Abstract
Two procedures for applying 13C n.m.r. spectroscopy to the quantitative analysis of the C1 C1a, and C2 components of gentamicin sulphate samples are described. One is based on the use of calibration plots of peak height ratios of analyte to standard (dioxan) resonance intensities recorded under conditions of full relaxation, the other upon a steady-state experiment and the use of weighting factors. Spectrometer operating conditions are discussed, and the need for measurement of longitudinal relaxation time (T1) data described. Results for seven commercial samples are given and comparisons made between the two n.m.r. methods and an h.p.l.c. procedure in terms of accuracy, specificity and convenience.
Penetration of nabumetone into inflammatory exudates in the rat
Authors: Haddock R E , Jeffery D J , Mangan F R , Pardon I S 
Published: April 2011

Abstract
The penetration of radioactivity into inflamed sites induced by subcutaneously implanted cotton pellets was studied in the rat after oral administration of [14C]nabumetone. Equilibration between inflamed site and plasma concentrations was slow, maximum concentrations in the pellet granuloma being later than those in the plasma. Nabumetone itself was found only in very low concentrations at the inflamed site and was not found in plasma. The major component (70%) of the radioactivity at both sites was the metabolite 6-methoxy-2-naphthylacetic acid, a compound which has anti-inflammatory properties. Elimination of radioactivity from the plasma and inflamed site was virtually complete within 24 h of dosing. Daily dosing with [14C]nabumetone confirmed that there was no progressive accumulation of radioactivity at the inflamed site.
Potent lipophilic substituted benzamide drugs are not selective D-1 dopamine receptor antagonists in the rat
Authors: Fleminger S , van de Waterbeemd H , Rupniak N M J , Reavill C , Testa B , Jenner P , Marsden C D 
Published: April 2011

Abstract
The substituted benzamide drugs YM 09151-2 and clebopride potently inhibited apomorphine-induced stereotyped behaviour in the rat and caused displacement of the specific binding of [3H]spiperone to D-2 binding sites on striatal membranes in low nanomolar concentrations. Other substituted benzamide drugs including metoclopramide, sultopride and flubepride also inhibited stereotyped behaviour to a greater or lesser degree, but were less potent in displacing [3H]spiperone from D-2 sites. YM 09151-2 and clebopride only weakly displaced specific binding of [3H]piflutixol to D-1 sites on rat striatal membranes, and only weakly inhibited striatal dopamine stimulated adenylate cyclase activity, when compared with cis-flupenthixol. The other substituted benzamide drugs did not displace [3H]piflutixol or inhibit dopamine stimulation of adenylate cyclase activity in the concentration range used. Clebopride and YM 09151-2 were highly lipophilic with apparent partition coefficient (log P') values equivalent to those of classical neuroleptic compounds, such as cis-flupenthixol. In contrast, the other substituted benzamide drugs were markedly less lipophilic. A log P' value of approximately 2 was required before inhibition of adenylate cyclase activity or displacement of [3H]piflutixol binding occurred. However, in excess of this value there was no correlation between either inhibition of adenylate cyclase activity or displacement of [3H]piflutixol binding and the lipophilicity of the various compounds. We conclude that potent lipophilic substituted benzamide drugs, like other members of the substituted benzamide series, are selective D-2 receptor antagonists. Inherent steric factors within the drug series would appear to dictate activity at D-1 and D-2 sites, although lipophilicity may contribute to actions in these environments.
[3H]Noradrenaline release evoked by selegiline ((-)-deprenyl) in the isolated main pulmonary artery of the rabbit*
Authors: Török Tamás L , Bunyevácz Zsuzsanna , Nguyen Tinh Thi , Magyar Kálmán 
Published: April 2011

Abstract
High concentrations of selegiline((-)-deprenyl) (&gt; 10−5 m) enhanced the nerve stimulation (2 Hz)-evoked release of [3H]noradrenaline from the isolated main pulmonary artery of the rabbit. This facilitation of stimulation-evoked [3H]noradrenaline release by selegiline was reduced by exogenous (-)-noradrenaline, an agonist of presynaptic α2-adrenoceptors. This inhibitory action of (-)-noradrenaline was partly antagonized by yohimbine, a selective α2-adrenoceptor blocker. When the stimulation-evoked [3H]noradrenaline release had already been incresed by inhibition of Na+-pump (K+-free solution), selegiline further enhanced the nerve-evoked release of labelled neurotransmitter.
Rifampicin induction of myopathy: lack of a direct effect on rat neuromuscular system
Authors: Renna G , Siro-Brigiani G , Conte-Camerino D 
Published: April 2011

Abstract
The effect of acute administration of rifampicin on neuromuscular transmission was tested, in-vivo, in the rat. Rifampicin did not alter the strength of contraction of the muscle indirectly stimulated at various frequencies. Additional isoniazid pretreatment did not alter the absence of effect of rifampicin on neuromuscular action.
Indirect adrenergic effect of histamine in human cerebral arteries: Influence of post-mortem period
Authors: Marco Emilio J , Balfagón Gloria , Conde María Victoria 
Published: April 2011

Abstract
Histamine (10−4 m) increased the radioactivity released from human cerebral arteries obtained within 6 h of death and preincubated with [3H]noradrenaline. In the presence of 10−6 m cocaine or if 7 or more hours had elapsed since death, 10−4 m histamine was unable to change basal levels of tritium outflow. The radioactivity retained by the tissue was higher when cerebral blood vessels were obtained within a post-mortem period of 6 h. These results suggest that histamine may release noradrenaline from the sympathetic innervation of human cerebral arteries and that the function of this innervation lasts only 6 h after death.
Analysis of the role of withdrawal state in morphine−induced supersensitivity to acetylcholine in mouse ileum
Authors: Ramaswamy S , Pillai N Padmanabha 
Published: April 2011

Abstract
An attempt has been made to study the possible role played by the withdrawal state in morphine−induced supersensitivity to acetylcholine in mouse isolated ileum. Chronic morphine treatment for 5 days produced a significant supersensitivity to acetylcholine in the ileum. This supersensitivity was not altered significantly by the addition of morphine to the bathing medium–−a measure to avoid the precipitation of the withdrawal state. This indicates that the supersensitivity obtained does not represent the state of withdrawal and is the result of chronic morphine treatment.