bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of antirheumatic drugs on protein sulphydryl reactivity of human serum
Authors: Hall Nicolas D , Gillan Anne H 
Published: April 2011

Abstract
The effect of a number of antirheumatic drugs on sulphydryl group reactivity in human serum has been determined using the thiol reagent, 5,5′-dithiobis (2-nitrobenzoic acid) (DTNB). Drug effects in vivo have been measured using sera from patients with rheumatoid arthritis receiving these compounds and the drugs have also been added to healthy human serum in vitro. An increased rate of sulphydryl-disulphide exchange between serum sulphydryl groups and DTNB was noted in rheumatoid disease. This finding was not associated with anti-inflammatory drug therapy. In vivo, non-steroidal anti-inflammatory drugs did not affect this reaction, but aurothiomalate, D-penicillamine and levamisole all significantly increased the rate of sulphydryl-disulphide exchange. When the drugs were added to healthy human serum in vitro, indomethacin, aurothiomalate and D-penicillamine stimulated sulphydryl reactivity with DTNB but levamisole had no effect. Aurothiomalate appeared to act in this system as a mixture of gold atoms and thiomalate molecules, the thiomalate stimulating and the gold inhibiting thiol reactivity. This study demonstrates that the stimulation of sulphydryl-disulphide exchange reactions in vivo is a property of three long-acting drugs used to treat rheumatoid arthritis, but not of non-steroidal antiinflammatory agents. This reactivity may therefore differentiate the second-line drugs showing true antirheumatic activity from ‘simple’ anti-inflammatory compounds. Comparative studies have shown that the addition of drugs to serum in vitro may give different results from those obtained with sera from rheumatoid patients receiving these agents. This may be due to in vivo metabolism of the compound, drug concentration effects or the parameters of the in vitro assay system. In view of this, caution is required in the interpretation of data obtained from in vitro studies of these compounds.
pA2 values of selective β-adrenoceptor antagonists on isolated atria demonstrate a species difference in the β-adrenoceptor populations mediating chronotropic responses in cat and guinea-pig
Authors: O'Donnell Stella R , Wanstall Janet C 
Published: April 2011

Abstract
pA2 values for atenolol (β1-selective) and α-methylpropranolol (β2-selective) have been determined on isolated atria of cat and guinea-pig using noradrenaline (β1-selective) and fenoterol (β2-selective) as agonists. On guinea-pig atria, the pA2 values did not vary with the agonist used. On cat atria the pA2 for atenolol was greater with noradrenaline than with fenoterol and the pA2 for α-methylpropranolol was greater with fenoterol than with noradrenaline. Fenoterol was 20 times more potent on cat than on guinea-pig atria whereas noradrenaline was approximately equipotent in the two species. The results have been interpreted as suggesting that both cat and guinea-pig atria contain one receptor type in common (β1) but that only cat atria contain β2-adrenoceptors as well.
The assay and stability of chlorpropamide in solid dispersion with urea
Authors: Ford James L , Stewart Alan F , Rubinstein Michael H 
Published: April 2011

Abstract
Thin layer chromatography followed by reflectance densitometry has been used to evaluate the stability of chlorpropamide-urea during the fusion process. Urea was found to decompose to biuret and chlorpropamide to p-chlorobenzenesulphonamide: several other unidentified decomposition products were detected. The energy for decomposition of chlorpropamide was 57·1 kJmol−1 for melts containing 15 and 30% chlorpropamide. Decomposition followed apparent first order kinetics.
Functional tolerance to ethanol in mice: relationship to lipid metabolism
Authors: Grieve Susan J , Littleton John M , Jones Paul , John Geryk R 
Published: April 2011

Abstract
The development of functional tolerance to ethanol was studied in young adult mice of the TO Swiss and C57BL strains. Ethanol administration was by intermittent inhalation for 7 h and the development of tolerance was assessed by estimating blood ethanol concentrations at successive losses of the righting reflex. The administration of (±)α-tocopherol at a dose previously shown to inhibit the effect of ethanol on peripheral phospholipid composition (750 mg kg−1 i.p.) was without effect on functional tolerance. Chronic administration of DL-carnitine, 7% w/w in diet for 10 days, a treatment previously shown to prevent ethanol-induced triglyceride accumulation, was also without effect on ethanol tolerance. Administration of the cholesterol synthesis inhibitor, diazacholesterol (30 mg kg−1 i.p.) 3 times per week for 3 weeks from weaning, markedly inhibited the subsequent development of functional tolerance. Administration of the inhibitor of protein synthesis, cycloheximide (300 μg kg−1 i.p.) greatly inhibited the development of ethanol tolerance whereas actinomycin D (100 μg kg−1 i.p.) was without effect. The results are discussed in relation to the hypothesis that ethanol cellular tolerance results from adaptation in the composition of the lipids of neuronal membranes. It is concluded that synthesis of some protein is involved in the development of cellular tolerance and also that cholesterol plays some part in the development of tolerance.
The effect of pyrogen on the in vivo metabolism and initial kinetics of chloroquine in rats
Authors: Osifo Nosakhare G 
Published: April 2011

Abstract
The possible contribution of hepatic metabolism impairment, caused by pyrogen, to the increased toxicity and altered pharmacokinetics of chloroquine in rats was investigated. The ratio of unchanged chloroquine (CQ) to total quinolines (TQ) was determined in the 24-h urine collection, the plasma and the liver. Pretreatment with massive doses of E. coli lipopolysaccharide pyrogen did not produce any significant change in the ratio of CQ/TQ in the urine, liver or plasma between control and pyrogen-treated rats. This finding occurred in spite of a pronounced initial behavioural effect of the pyrogen on the rats. The ratio of CQ/TQ was also preserved in the 7th day 24-h urine collection from a control and a pyrogentreated rat although the total urinary excretion of TQ had decreased by about 99·5% of the first 24-h collection. Analysis of the pharmacokinetic parameters from plasma levels in the first 24 h showed significant alterations in the apparent volume of distribution (AVD), the half-life (T 1/2) and the rate of decay constant (K) of the drug in pyrogen-treated rats. These findings were interpreted to indicate that chloroquine metabolism in vivo, which occurs mainly via a dealkylation process, may not be readily deranged by pyrogen. The changes in the pharmacokinetic parameters are discussed in relation to the known haemodynamic changes that occur in the febrile state.
Monoamine oxidase inhibition and brain amine metabolism after oral treatment with toloxatone in the rat
Authors: Keane P E , Kan J P , Sontag N , Benedetti M Strolin 
Published: April 2011

Abstract
Rats were administered toloxatone 100 mg kg−1 p.o., and killed 0·5 to 8 hours later. Toloxatone reversibly inhibited type A MAO, but did not affect the activity of type B MAO in whole brain. Cerebral concentrations of noradrenaline, dopamine and 5-hydroxytryptamine were increased after toloxatone, while their metabolite concentrations were reduced. Synaptosomal uptake processes of these amines were not altered by toloxatone.
Reduction in blood pressure in normal and spontaneously hypertensive rats by lergotrile mesylate
Authors: Sved Alan F , Fernstrom John D 
Published: April 2011

Abstract
The acute administration of lergotrile mesylate to normal or spontaneously-hypertensive rats (SHR) causes a prompt reduction in blood pressure. In SHR, doses as small as 0·05 mg kg−1 are effective; maximal reductions in blood pressure are obtained at a dose of 0·25 mg kg−1. Lergotrile may be administered intraperitoneally or orally. Its efficacy as an antihypertensive agent in rats does not diminish significantly when administered twice daily for 7 days. Although lergotrile has been reported to be a dopamine agonist, the present data do not establish the mechanism by which the drug lowers blood pressure.
Release of [3H]noradrenaline induced by 5-hydroxy-tryptamine from cat pial arteries
Authors: Marin J , Salaices M , Sánchez C F 
Published: April 2011

Abstract
Pial arteries of cats were used to analyse the effects of 5-hydroxytryptamine (5-HT) on the release of [3H]noradrenaline. To achieve this the vessels were preincubated with [3H]noradrenaline and the effect of different concentrations of 5-HT (10−6, 10−5, 10−4 M) on the release of tritium was studied. 5-HT elicited release of radioactivity in a dose-dependent manner. Removal of both superior cervical sympathetic ganglia 15 days before the experiment or pretreatment of the animals with reserpine (3 mg kg−1, total dose) produced a significant decrease in the outflow of tritium induced by 5-HT. In these arteries, the amount of radioactivity retained at the end of the experiment was much diminished. Cocaine (10−6 M) caused a significant decrease in the tritium efflux induced by 5-HT (10−5 M). These results show that 5-HT has an indirect adrenergic effect in the pial arteries of the cat only at high doses of 5-HT, and confirm that sympathetic innervation of these vessels mainly comes from the superior cervical ganglia.
Methysergide induces selective potentiation in cholinergic contractions of the guinea-pig vas deferens by facilitating acetylcholine release
Authors: Katsuragi Takeshi , Furukawa Tatsuo 
Published: April 2011

Abstract
Methysergide (3 times 10−6 M) enhanced the contractile responses of the isolated stripped vas deferens of guinea-pig to acetylcholine(ACh) and arecoline, but not those to noradrenaline, tyramine and bradykinin. Methysergide (3 times 10−5 M) suppressed the contraction elicited by noradrenaline or histamine. The methysergide-induced potentiation of the response to ACh was prevented by pre-addition of hemicholinium but not by tetrodotoxin or morphine. The augmentation of the response to ACh by physostigmine was unaffected by hemicholinium. The phasic contraction of the tissue elicited by 30 mM KCl was also enhanced by methysergide, and this enhancement was prevented by the pre-addition of atropine (1·4 times 10−7 M). In the depolarized vas deferens after exposure to 30 mM KCl, methysergide occasionally induced a sustained tonic contraction which was inhibited by atropine. These findings suggest that methysergide facilitates a release of ACh by acting on the cholinergic nerve terminals and selectively potentiates the cholinergic response.
The effects of bromocriptine on pre-synaptic and post-synaptic α-adrenoceptors in the mouse vas deferens
Authors: Gibson Alan , Samini Morteza 
Published: April 2011

Abstract
Noradrenaline (NA) and dopamine (DA) contracted the mouse vas deferens and reduced the responses to low frequency nerve stimulation (0·1 Hz). The relative potencies of antagonists suggested that these effects were due to stimulation of post-synaptic and pre-synaptic α-adrenoceptors respectively. Bromocriptine produced a non-competitive antagonism of contractile responses to NA (pD2′ = 7·6) and DA (pD2′ = 8·0) but had no effect on responses to carbachol. Bromocriptine also reduced single twitch responses of the vas to low frequency field stimulation (0·1 Hz), but did not affect stimulation at higher frequencies (1·20Hz). Yohimbine selectively and rapidly reversed the inhibiting effects of bromocriptine on single twitches, although they could not easily be reversed by washing. Bromocriptine produced a yohimbine-reversible reduction in the stimulated overflow of tritium from vasa previously loaded with 3H-NA. Thus the mouse vas deferens does not appear to contain specific DA receptors and the results suggest that bromocriptine acts as a pre-synaptic α-adrenoceptor agonist and post-synaptic α-adrenoceptor antagonist in this tissue.
Stereoselectivity of some oxotremorine antagonists containing two chiral centres
Authors: Ringdahl Björn , Resul Bahram , Dahlbom Richard 
Published: April 2011

Abstract
The stereoisomers of some analogues of oxotremorine containing two chiral centres, one in the 1-position of the butynyl chain and one in the 2-position of the pyrrolidine ring, have been prepared. The compounds are oxotremorine antagonists. They show a marked stereoselectivity, which depends mainly on the configuration of the chiral centre in the butynyl chain and to a lesser extent on the configuration of that in the pyrrolidine ring.
Effect of contaminating proteolytic activity upon insulin and insulin-protamine complex
Authors: Caygill Christine P J , Ayling Christine M 
Published: April 2011

Abstract
The proteolytic contamination in batches of various insulin preparations was studied using chromogenic synthetic peptide substrates, synthetic ester substrates, and a test similar to the European Pharmacopoeia test for ‘Limit of Proteolytic Activity’. In order to study the latter test, insulin-protamine complexes were prepared using salmine sulphate and samples of crystalline insulin, some of which contained peptidase activity. All insulin-protamine complexes prepared from insulin crystals in which peptidase activity had been detected using a synthetic chromogenic substrate were degraded on storage at 37 °C, whereas those prepared from insulin crystals in which no peptidase activity could be detected showed no significant loss in weight. Chromatography on Sephadex G50 revealed degradation of insulin in solutions containing traces (∼0·5 p kat mg−1 preparation) of peptidase activity and stored for 2 weeks at 37 °C at pH 7·4, but not of such insulin stored at pH 2·5 at 37 °C for up to 6 weeks. Since insulin preparations formulated at neutral pH are so susceptible to molecular degradation by traces of peptidase contamination, it is suggested that the test using a chromogenic peptide substrate could be applied to bulk crystals before vialing of insulin preparations and could also replace the current test specified in the monograph on Isophane Insulin of the European Pharmacopoeia.
Preliminary evaluation of dika fat, a new tablet lubricant
Authors: Udeala O K , Onyechi J O , Agu S I 
Published: April 2011

Abstract
Dika fat, a solid vegetable oil extracted from the kernels of Irvingia gabonensis var excelsia has been evaluated as a lubricant* on the basis of its effect on the flow rate of granules, disintegration time and dissolution rate of tablets. The fat shows a maximal effect on flow at a concentration of 2·5% w/w. It produces better disintegration and dissolution profiles than magnesium stearate at all concentrations tested. The indication is that there is less degradation of aspirin in tablets containing this oil than there is in tablets containing magnesium stearate. The use of Dika fat(m.p. 39–40 °C) eliminates the hydrogenation step often necessary for vegetable oils.
Effect of ethylcellulose grade and sealant treatments on the production and in vitro release of microencapsulated sodium salicylate
Authors: Deasy P B , Brophy M Regina , Ecanow B , Joy Mary M 
Published: April 2011

Abstract
Sodium salicylate was microencapsulated with ethylcellulose 100 cp by polymer deposition from cyclohexane by temperature change to give a finer product, with slower drug release, than that obtained with 10 cp grade of ethylcellulose. Scanning electron microscope and polymer disc swelling studies confirmed that larger microcapsules after drug release ruptured into smaller particles with swollen surfaces containing pores. Treatment of microcapsules with paraffin wax solution retarded release of core material, the release being affected by the percentage of sealant used and the particle size of the product. The mechanism of release from the sealed microcapsules was complex involving mainly diffusion, but polymer erosion and drug binding were also involved. Other sealant materials were less effective in retarding dissolution.
Cannabinoid compounds in South African Cannabis sativa L
Authors: Field B I , Arndt R R 
Published: April 2011

Abstract
Dagga (Cannabis sativa L.) samples were collected from various geographical regions of South Africa. These were classified into age, sex and plant part and the cannabinoids were analysed quantitatively by gas-liquid chromatography and mass spectrometry. Analytical results show that there appears to be at least three chemovariants of Cannabis sativa growing in South Africa with respect to relative cannabinoid content. One of these variants appears to be unique to Southern Africa. It also appears that South African C. sativa ranks among the world's more potent C. sativa variants in terms of its Δ9 -tetrahydrocannabinol content.
Mitomycin C-dextran conjugate: a novel high molecular weight pro-drug of mitomycin C
Authors: Kojima T , Hashida M , Muranishi S , Sezaki H 
Published: April 2011

Abstract
A high molecular weight derivative of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D) has been synthesized and its biological and pharmacological properties investigated. MMC is released from MMC-D in vitro with a half-life of 24 h. After intraperitoneal injection of MMC-D, free MMC could be detected in plasma and urine of mouse for 5–8 h, while MMC administered as a free form was eliminated rapidly. After MMC-D, given to mice bearing Ehrlich ascites carcinoma or B16 melanoma there was a reduction in toxicity and an increase in survival time compared with MMC. These observations suggest that the high molecular weight MMC-dextran derivative is a kind of pro-drug which persists in the body giving a sustained release of free MMC thus significantly increasing the antitumour activity of the parent drug.
Some preliminary observations of the nephrotoxicity of the male antifertility drug (±)α-chlorohydrin
Authors: Morris I D , Williams L M 
Published: April 2011

Abstract
(±)α-Chlorohydrin (80 mg kg−1) given by mouth to group-housed adult male Sprague Dawley rats produced an increase in the weight of the kidneys which persisted for at least 7 days, but there were no deaths. This dose administered to Sprague Dawley rats caged singly killed 3 out of 8 animals. The toxicity was studied in more detail using Wistar rats caged singly in metabolic cages. 4 out of 9 animals died with oliguria and anuria after 120mg kg−1 (±)α-chorohydrin, 100 and 120 mg kg−1 (in the surviving animals), produced a loss in appetite and body weight, proteinuria, a dose-related diuresis and an increased water intake. Urinary glucose was dramatically elevated after 100 mg kg−1 but after 120 mg kg−1 the glucosuria was not as marked. By day 7 all parameters were returning to their pre-injection values. A dose of 80 mg kg−1 had no effect upon any of the parameters studied. The results are discussed in relation to the basic biochemical mechanism by which the drug exerts its antifertility action, which is achieved at much lower doses.
The binding of [3H] pargyline to rat liver mitochondrial monoamine oxidase
Authors: Parkinson David , Callingham Brian A 
Published: April 2011

Abstract
The synthesis and purification of tritium labelled N-desmethylpargyline and pargyline are described. The suitability of these irreversible suicide inhibitors of monoamine oxidase (MAO) as ligands in binding studies to rat liver mitochondrial MAO has been evaluated. [3 H] Pargyline was found to be more satisfactory than its N-desmethyl analogue because of its greater potency and lower proportion of non-specific binding. The binding of pargyline reached saturation when about 31 pmol mg protein−1 was bound. It was not possible to explain the time course of the binding by either simple first or second-order kinetics. [3 H]-Pargyline is a potentially valuable ligand for the estimation of the concentration of MAO active centres without the need to remove the enzyme from the mitochondrial membrane.
Species differences in clobazam metabolism and antileptazol effect
Authors: Caccia S , Guiso G , Samanin R , Garattini S 
Published: April 2011

Abstract
The antileptazol effect of clobazam lasts longer in the mouse than in the rat. After intraperitoneal injection of clobazam (10 mg kg−1) plasma and brain concentrations of the drug and its rate of disappearance were similar in both species, whereas the metabolite N demethylclobazam was present at higher concentrations and for longer in the mouse than in the rat. Although the exact contribution of the N-desmethylclobazam to the anticonvulsant effect of clobazam cannot be assessed, the longer duration in mice than in rats seems to be associated with different brain accumulations of the metabolite.
Effective intestinal absorption of insulin in diabetic rats using a new formulation approach
Authors: Touitou Elka , Donbrow Max , Rubinstein Ardon 
Published: April 2011

Abstract
Insulin injected intra-jejunally together with the non-ionic surfactant cetomacrogol was effective in streptozocin-induced diabetes in the rat, as measured by the hypoglycaemic effect. The reduction in blood sugar was maximal at about 2 h after administration but continued at a high level for the 4 h of the experiment. No hypoglycaemic effect was observed in controls injected with insulin or saline alone. Intestinal absorption of insulin has thus been effected by the addition of cetomacrogol, which appears to enhance membrane-permeability to insulin rather than to function as a protective agent preventing insulin degradation, as in liposome-encapsulation. In support of this, a significant hypoglycaemic action was still obtained when the insulin injection was given half-hour after that of the cetomacrogol, both intra-jejunally. Furthermore, oral administration of the surfactant followed by intra-jejunal injection of the insulin also gave a hypoglycaemic effect. The use of this agent to enhance insulin absorption offers the possibility of a new approach to oral insulin therapy.
The molecular weight and molecular weight distribution of hydroxypropyl methylcellulose used in the film coating of tablets
Authors: Rowe R C 
Published: April 2011

Abstract
The molecular weight and molecular weight distributions of nine grades of hydroxypropyl methylcellulose used in the film coating of tablets have been measured using gel permeation chromatography. With the exception of Pharmacoat 603, there is a high molecular (&gt;5 times 105) component present in all grades ranging from relatively small amounts in grades with low nominal viscosity to relatively large amounts in the 50 mPas grade. The peak molecular weight taken from the distribution curve—an indication of the molecular weight of the main component—could be calculated from the nominal viscosity using the equation. Peak molecular weight = 23·54 times 103 (viscosity)0·45. The relationship could also be expressed in the standard form [η] = KMα where M is the peak molecular weight [η] is the intrinsic viscosity and K and α are constants (in this case 9·94 times 10−4 and 1096 respectively). The wide molecular weight distribution of these samples and the presence of quite high proportions of very low molecular weight (&lt;5 times 103) components especially in samples with nominal viscosity designations of less than 15 mPas appears to affect their mechanical properties.