Showing papers by "Imperial Chemical Industries published in 1977"

Direct evidence for an interaction of β-adrenergic blockers with the 5-HT receptor

Abstract: ADVANCES in neurotransmitter receptor identification and quantification by biochemical techniques involving radiolabelled analogues of putative neurotransmitters have led to the characterisation of a number of receptor systems in mammalian brain tissue1; these include the catecholamines2,3, 5-HT4, glycine5 and GABA6 receptors. The development of these techniques has provided a means of screening chemical compounds for their effects on different receptor systems7. The central nervous system effects of (±)-propranolol (Inderal, ICI) in animals are well documented8,9. This drug has therapeutic benefit in man in anxiety10, and is also reported to have similar benefit in schizophrenia11,12, essential tremor13 and drug dependence14. The origin of these effects is not understood but theories about its mode of action include β-adrenergic blockade15, membrane stabilisation8 and a 5-HT receptor blocking action16,17. We report here that propranolol a stereospecific affinity for the 5-HT receptor from rat brain which is similar in magnitude to the putative 5-HT receptor blocking drug methylsergide.

Stretching flow instabilities at the exits of extrusion dies

Abstract: As liquid leaves an extrusion die, the surface layers are rapidly stretched. Stretching flows may become unstable in two ways: by breaking, or in a ductile manner producing an uneven “necked” sample which, in continuous extrusion and drawing, is sometimes called “draw resonance”. There is a quantitative correlation between the extrusion defect known as “sharkskin” and the cohesive failure of polymer melts. By extruding under closely defined conditions, it is possible to introduce a transitory “structure” into the surface layer of the extrudate greatly enhancing its cohesive strength and eliminating this defect. A similar quantitative correlation is established between the uneven coating thickness sometimes obtained during coextrusion of a high viscosity melt on the surface of a low viscosity melt and the tensile drawing instability known as “draw resonance”. Simple criteria are established to avoid this problem in practical flow engineering.

Magnetic particles for immunoassay

Abstract: This invention relates to magnetic particles and to the use thereof. Each particle comprises a low density core and a component therewith, at least a portion of the surface of the core being coated with magnetic material.

Urogastrone levels in the urine of normal adult humans.

Abstract: Urogastrone is a potent inhibitor of gastric acid secretion isolated from human urine and it is structurally related to and shares the properties of a potent mitogen-mouse epidermal growth factor. The amounts of urogastrone in 24 h normal human urine samples were measured using a specific and sensitive radioimmunoassay. Values varied from 120–1360 ng/kg/24 h but a significant difference (2P < 0.005) was observed between urine samples from men (602 ± 41 SE, n = 39) and women (782 ± 44 SE, n = 33). A series of 24 h urine collections from male and female volunteers showed that wide variations could occur over a 4 week period in the individual output of urogastrone. Levels from women did not show variations that could be related to the stage of the menstrual cycle.

Sustained release pharmaceutical composition

Abstract: Sustained release pharmaceutical composition consisting of a hard gelatine capsule containing film coated spheroids, the spheroids comprising propranolol, or a pharmaceutically-acceptable salt thereof, in admixture with non-water-swellable microcrystalline cellulose, and the said spheroids having a film coat comprising ethylcellulose optionally together with hydroxypropyl methylcellulose and/or a plasticizer.

Voided films of polyester with polyolefin particles

Abstract: Opaque voided films having a total luminous transmission not exceeding 25% are made from blends of a polyester preferably polyethylene terephthalate, with 3 to 27% of an ethylene or propylene polymer, prepared by dry blending One end use of the film, as a base for photographic prints is also described

Pulmonary ultrastructure after oral and intravenous dosage of paraquat to rats.

Abstract: Paraquat was administered to rats by gavage or intravenously at doses which were approximately equitoxic (680 mu. moles/kh and 65 mu. moles/kg respectively) and the lungs examined by light and electron microscopy at intervals up to 48 hours. No significant changes were observed in alveolar endothelial cells at any of the time intervals studied. After intravenous administration the first ultrastructural changes were observed at 4 hr in the type I cells which were less electron dense and contained few organelles. At 8 hr these lesions were more marked and in some places the basement memebrane was denuded. Type II cells were also showing damage to mitochondria and loss of microvilli. After oral dosing, the type and sequence of changes was similar but the first changes were not seen until 22 hr. Intravenous injection of 0-03 micron carbon particles 1 hr before killing showed no significant leakage from the alveolar endothelium. This study provides no morphological evidence that the oedema of the lung caused by paraquat in rats is due to damage to endothelial cells. It appears that, following dosing by the two routes, the difference in interval between dosing and the development of lesions is due to the accumulation of paraquat. Lesions in type I cells therefore occurred when a certain concentration of paraquat is known to be present in the lung. It is suggested that a prime compartment into which paraquat is accumulated is the alveolar epithelial cell.

Antibacterial properties of Hibitane

Abstract: The key features of the interaction of chlorhexidine with bacteria leading to death are adsorption, damage to permeability barriers and precipitation of the cytoplasm. The bacteriostatic profile indicates that Streptococcus mutans is highly susceptible but it is not known whether bacteriostatic or bactericidal activity is crucial to antiplaque activity. Although some correlation overall was found between bactericidal and bacteriostatic susceptibility amongst more than 80 strains of various species, reference to the minimum inhibitory concentration alone gives no firm indication about the possible lethal action of chlorhexidine. The effects of saliva and pH on antibacterial activity are given. In human studies reported by others, repeated oral application of chlorhexidine reduced the numbers of salivary organisms recoverable and this was accompanied by slight (seemingly clinically insignificant) alterations in the sensitivity of certain salivary organisms. Daily application of a chlorhexidine dental gel in a 6-week trial did not result in detectable changes of susceptibility of the salivary flora. Rats dosed daily in drinking water (5-10 mg chlorhexidine base per kg) over a 2-year period yielded buccal organisms with reduced sensitivity: this was not reflected amongst faecal bacteria. The faecal flora changed quantitatively in a dose-dependent manner and coliform organisms particularly were reduced in number. Caution is required in interpreting relative sensitivities of different bacterial strains or species from data obtained using agar-diffusion methods.

The Contribution of Ethological Techniques to the Study of Drug Effects

Abstract: Centrally acting drugs, by definition, influence the function of the nervous system and therefore inevitably affect behavior, and indeed the desired effect of such drugs is, in general, alteration of behavior. In addition, many other drugs may have behavioral side effects, and a variety of adventitious substances such as solvents and pesticides have also been reported to modify the actions and outlook of those encountering them. Investigation of the action of these agents therefore includes the need to measure behavioral change. This measuring must be done both qualitatively, so that the type of behavior influenced can be recognized, and quantitatively, so that the magnitude of the effect can be estimated. The success of any procedure that is to evaluate the behavioral effects of a drug therefore depends on the ability of the procedure to discriminate among different types of behavior and on its susceptibility to accurate measurement.

Relationship between blood level of atenolol and pharmacologic effect.

Abstract: Thirty-five hypertensive patients were treated with atenolol in weekly increasing doses (25, 50, 100, and 200 mg thrice daily). Factors determining the blood level of the drug were studied along with the relationship between blood level, the degree of cardiac beta blockade, and the antihypertensive effect of the drug. The blood level obtained varied with the daily dose, the time of blood sampling during the day, the body weight, and the creatinine clearance. The degree of beta blockade was assessed by measuring maximum-exercise tachycardia and was correlated with the blood level of atenolol. The reduction of the maximum exercise heart rate was independent of age. The hypotensive effect was not closely correlated with the blood level. Three days after the termination of long-term atenolol treatment, blood levels and beta blockage were still detectable.

Fibre expanded reinforced materials and their process of manufacture

Abstract: A very low density material is produced by extruding a composition comprising a settable fluid containing long resilient fibres through a narrow die under conditions which cause the extrudate to expand to form an open fibrous structure as it leaves the die, and then causing the fluid to set. This is applicable to both thermoplastic and thermosetting materials. Various coating layers may be applied to provide rigid light-weight panels and shaped articles for various uses including furniture and building applications.

Safety of Hibitane. II. Human experience

Abstract: Chlorhexidine has been widely used in medical practice since its introduction on to the marked in the early 1950s. Primarily it has been used for topical antisepsis, e.g. pre-surgery skin preparation, burns prophylaxis, and prior to obstetrical/gynaecological procedures. This extensive experience has demonstrated the virtual absence of sensitization and a low irritancy potential for the compound. Only one significant adverse effect has been identified during medical use, namely, the production of sensorineural deafness after direct instillation into the middle ear, a property shared by several commonly used antiseptics. The encouraging reports of the use of chlorhexidine for plaque control prompted further safety investigations. It has been shown that absorption after oral ingestion is very low, and long-term oral use has not produced changes in haematological and biochemical parameters. Occasional oral intolerance of mouthrinse formulations has been reported, although no histological abnormalities were present in gingival biopsies taken after 18 months' daily use. Very occasionally, a reversible swelling of the parotid glands has been reported after use of chlorhexidine in mouthrinse formulations, but not after other methods of administration. Tooth discoloration, which shows wide inter-individual variation is seen after all dental formulations. This undesirable cosmetic effect would appear to represent the only significant argument against everyday prophylactic oral use of chlorhexidine.

Shear thinning and thickening rheology

Abstract: Particles with radii 21–1010 nm, of methyl methacrylate homopolymer or copolymers with ethyl acrylate, were dispersed in high-boiling hydrocarbons. The stabilizer contained poly(12-hydroxystearic) acid. Viscosities at shear rates of 1–104 sec−1 were measured with cone and plate (Weissenberg rheogoniometer), becoming steady almost instantaneously. Severe shear thickening prevented continuing flow when the particle volume fraction exceeded about 47%. Shear thinning occurred at shear rates below 100 sec−1. Dispersions of one copolymer had lower viscosities than those of homopolymer. Blending two sizes of particles reduced the viscosity, so that the volume fraction of a homopolymer blend could be raised to 54% without severe shear thickening. The shear-thinning behavior at the lower concentrations is correctly represented by the Cross equation; analysis of the parameters in it suggests that two mechanisms operate, one possibility being partial collapse of the layer of stabilizer around each particle.

The biochemical mode of action of some modern anthelmintics

Abstract: The possible biochemical modes of action of levamisole, morantel, benzimidazoles and salicylanilides are discussed. It is concluded that the modes of action of none of these anthelmintics is properly understood, but it seems likely that levamisole and pyrantel act on the nematode nervous system, benzimidazoles affect cellular integrity and the uncoupling properties of salicylanilides could enable them to act at several sites.

Safety of Hibitane I. Laboratory experiments

Abstract: The safety evaluation of chlorhexidine (Hibitane) in animal species will be briefly reviewed. The relevance of these studies to human use will be discussed, and species comparisons made where possible. Animal studies with chlorhexidine were begun more than two decades ago and the evaluation of its safety has been under continual review ever since. Chlorhexidine is poorly absorbed after oral administration, well tolerated after parenteral administration and its percutaneous absorption is abolutely minimal. No clinical or histological effects have been obtained in any animal study to cause hesitation in the light of proliferating applications of chlorhexidine in human use. The various toxicological studies in animals will be described and in particular the results of a 2-year study in rats will be outlined. In this, as an in earlier long-term study, there were no effects whatsoever to suggest that chlorhexidine treatment could give rise to any kind of tumourigenic effect or any other toxic sign.

Selective hydrogenation of highly unsaturated hydrocarbons in the presence of less unsaturated hydrocarbons

Abstract: A catalyst for selective hydrogenation of highly unsaturated hydrocarbons in the presence of less unsaturated hydrocarbons comprises palladium supported on alumina having a defined combination of micromeritic properties, the palladium being present mainly in the regions of the catalyst particles not more than 150 microns beneath their geometric surface. The alumina is made suitably by calcining pseudobohmite at 1000°-1200° C. The catalyst has a long working life in "front-end" or "tail-end" hydrogenation.

Method of injection-moulding onto a preformed web

Abstract: In a method of injection-moulding articles of plastics material onto a preformed web inserted into the mould, the web is held under substantially constant tension during the closing of the mould, between a pair of clamps, the proximal clamp being fixed relative to the mould and the distal clamp free but bearing a load to furnish the desired tension in the web. The load may be imposed by a weight attached to the distal clamp, conveniently by means of an electromagnet.

Production of maleic anhydride and catalysts therefor

Abstract: Catalysts for the oxidation of hydrocarbons to maleic anhydride comprise a phosphorus/vanadium mixed oxide promoted by tungsten antimony, niobium, and/or molybdenum, having a surface area of at least 10m 2 /g.

Energy process in methanol synthesis

Abstract: In a process in which, after product recovery, an off-gas containing hydrogen and/or carbon monoxide is produced, energy economy is improved by reacting the off-gas in a fuel cell. The resulting electricity is preferably used for driving small machines in the process. The process is especially useful for producing methanol from natural gas feedstock and then includes the steps of methanating the off-gas and letting it down in an engine before passing it to a fuel cell.

Ammonia synthesis process

Abstract: Ammonia synthesis gas is made from a raw gas comprising hydrogen, carbon dioxide and medium boiling point gases including nitrogen in excess of the proportion required in ammonia synthesis gas, by a pressure swing adsorption process characterized by feeding to the adsorbent a raw gas in which hydrogen and total medium boiling point gases are present in a volume ratio in the range 1.25 to 2.5, and the medium boiling point gases comprise nitrogen to the extent of at least 90% v/v on the total such gases. Preferred ways of making the raw gas, of ensuring purity of the product gas and of recovering useful heat are described.

Polyurethane foam containing internal mold-release agent

Abstract: A mold-release agent is provided which consists essentially of 99.9% to 80% by weight of an aromatic polyisocyanate containing at least two isocyanate groups and 0.1% to 20% by weight of a fatty acid ester, e.g., glycerol trioleate, olive oil, peanut oil, etc. A process of using the material by incorporating it in polyurethane foams is disclosed.

The selective action of beta-adrenoceptor blocking drugs and the nature of beta1 and beta2 adrenoceptors.

Abstract: 1 Purified membranes retaining a catecholamine responsive adenylate cyclase have prepared from rabbit heart, lung and (pseudo-pregnant) uterus. 2 These preparations have the characteristics of plasma membranes and both heart and lung respond to beta-adrenoceptor agonists in the order: (+/-)-isoprenaline greater than (-)-noradrenaline greater than (-)-adrenaline greater than (+)-isoprenaline greater than salbutamol. The sensitivity of the adenylate cyclase to beta-adrenoceptor stimulation is improved by pre-treatment of the animals with reserpine and syrosingopine. 3 Dose-ratios for several concentrations of propranolol (non-selective beta-adrenoceptor blocker), practolol and atenolol (cardio-selective beta-adrenoceptor blockers) have been measured on all three membrane preparations. Schild plots of log (dose ratio -1) vs. log dose were virtually coincident for heart and lung with a dissociation constant (Kb) for propranolol very close to the pharmacological value. The ratio of Kb values was 0.65 for practolol and 1.23 for atenolol compared with pharmacological cardio-selectivity ratios (measured on isolated atria and tracheal chain) of 67.6 and 110 respectively. The uterus/heart Kb ratio was 51.5 for atenolol. Inhibition of the uterus by practolol gave a Schild plot with slope significantly less than 1, indicating a different mechanism of action from the heart. 4 Kb values obtained by measuring adenylate cyclase stimulation in chopped tissue (including preparations of bronchial tree and alveolar tissue as well as whole lung) resembled the membrane values rather than those found in whole organs. 5 The results show that the pharmacological selectivity of practolol and atenolol is maintained at the receptor-adenylate cyclase level, at least as far as heart and uterus are concerned, though the smaller selectivity ratios in the biochemical system suggest that receptor differences is not the only factor and that phase distribution of the drug may also be important. Membranes prepared from whole lung show that phase distribution of the drug may also be important. Membranes prepared from whole lung show an overall beta1 response which may simply reflect the predominance of beta1 cell types containing beta1-adrenoceptors over bronchial smooth muscle.

Shaped explosive charge device for under water use

Abstract: In the use of a shaped explosive charge device underwater, the stand-off and cavity chamber are filled with compressed gas which is fed into the chamber to expel water through one or more apertures communicating with the surrounding water. Conveniently the apertures remain open and the compressed gas is entrapped and maintained within the device by the ambient hydrostatic pressure.