Showing papers by "Imperial Chemical Industries published in 1968"

The biological properties of the optical isomers of propranolol and their effects on cardiac arrhythmias

Abstract: 1. The optical isomers of propranolol have been compared for their β-blocking and antiarrhythmic activities. 2. In blocking the positive inotropic and chronotropic responses to isoprenaline, (+)-propranolol had less than one hundredth the potency of (-)-propranolol. At dose levels of (+)-propranolol which attenuated the responses to isoprenaline, there was a significant prolongation of the PR interval of the electrocardiogram. 3. The metabolic responses to isoprenaline in dogs (an increase in circulating glucose, lactate and free fatty acids) were all blocked by (-)-propranolol. (+)-Propranolol had no effect on fatty acid mobilization but significantly reduced the increments in both lactate and glucose. 4. Both isomers of propranolol possessed similar depressant potency on isolated atrial muscle taken from guinea-pigs. 5. The isomers of propranolol exhibited similar local anaesthetic potencies on an isolated frog nerve preparation at a level approximately three times that of procaine. The racemic compound was significantly less potent than either isomer. 6. Both isomers of propranolol were capable of preventing adrenaline-induced cardiac arrhythmias in cats anaesthetized with halothane, but the mean dose of (-)-propranolol was 0.09±0.02 mg/kg whereas that of (+)-propranolol was 4.2±1.2 mg/kg. At the effective dose level of (+)-propranolol there was a significant prolongation of the PR interval of the electrocardiogram. Blockade of arrhythmias with both isomers was surmountable by increasing the dose of adrenaline. 7. Both isomers of propranolol were also capable of reversing ventricular tachycardia caused by ouabain in anaesthetized cats and dogs. The dose of (-)-propranolol was significantly smaller than that of (+)-propranolol in both species but much higher than that required to produce evidence of β-blockade. 8. The implications of these results are discussed.

The action of paraquat and diquat on the respiration of liver cell fractions

Abstract: 1. Paraquat and diquat produce only a slight increase in the oxygen uptake of rat liver mitochondria, and it is likely that they do not penetrate the mitochondrial membrane. 2. In mitochondrial fragments inhibited by antimycin A or by Amytal, both substances stimulate oxygen uptake with NADH or β-hydroxybutyrate as substrate but not with succinate. The NADH dehydrogenase of the respiratory chain appears to be involved, at a site only partially inhibited by Amytal. 3. An NADPH oxidase activity is stimulated in rat liver microsomes by diquat, and to a smaller extent by paraquat; diquat also causes an NADH oxidase activity to develop. The effect is not inhibited by carbon monoxide or p-chloromercuribenzoate, and it is probable that a flavoprotein is involved by a mechanism not requiring thiol groups. 4. One molecule of oxygen can oxidize two molecules of NADPH in the stimulated microsomal system, the hydrogen peroxide produced being broken down by a catalase activity in the microsomes. 5. Diquat can stimulate NADH oxidase and NADPH oxidase activity in the postmicrosomal soluble fraction; the enzyme involved may be DT-diaphorase. 6. The mechanism of these reactions and their significance in relation to the toxicity of the dipyridilium compounds are discussed.

Structure-function relationships in gastrin-like peptides

Abstract: As the work leading to the elucidation of the structures of the hog gastrins was nearing completion and the synthesis of the hormones was being planned, it became clear that the glycine residue at position 13 offered a convenient dividing point in the synthesis. Our colleagues at Liverpool subsequently became concerned with the synthesis of 1-13 fragments and we with the synthesis of the 14-17 fragment, Try-Met-Asp-Phe-NH 2 , of the molecules. Not long afterwards the tetrapeptide amide had been synthesised and found by Tracy & Gregory (1964) to possess all the physiological properties of the natural hormones. The finding of activity in so small a ‘stump’ of the molecule offered scope for an investigation of structure-function relationships on a scale not hitherto possible with polypeptide hormones. We attached value to such an investigation on two accounts. First, the results might contribute towards our knowledge of the mode of action of the gastrins and polypeptide hormones in general. Secondly, conclusions enabling a more rational approach to the design of inhibitors of the action of polypeptide hormones might be provided. Both expectations were clearly pertinent to an objective of our researches—the development of therapeutic agents of value in the assessment and control of gastric secretory function in humans. For the purposes of the investigation we prepared about 500 derivatives or analogues of the tetrapeptide amide comprising: ( a ) various N -terminally acylated derivatives of the tetrapeptide amide, ranging from simple derivatives like the acetyl (Ac-Try-Met-Asp-Phe-NH2) to extended peptides like the hexadecapeptide amide sequence (2-17) of human gastrin (H-Gly-Pro-Try-Leu-(Glu)5-Ala-Tyr-Gly-Try-Met-Asp-Phe-NH2), ( b )analogues derived by single replacements at the five main positions in the tetrapeptide amide (the four amino-acid and the terminal amide positions), and ( c ) analogues derived by two or more replacements at the five positions. The tripeptide amide, H-Met-Asp-Phe-NH2, dipeptide amide, H-Asp-Phe-NH2, and various analogues of these compounds were also prepared and examined, but since in general these were devoid of biological activity they will not be discussed. Thirty-three derivatives or analogues of the tetrapeptide amide were selected and examined in the conscious dog in the Physiological Laboratory, University of Liverpool; the results describing their influence on gastric acid secretion, gastric motility, intestinal motility, pancreatic secretion, gastric motility, intestinal motility, pancreatic secretion, and pepsin secretion have been reported (Morley, Tracy & Gregory 1965). The present paper concerns results obtained in rats in our own laboratories with a larger group of the compounds in respect of acid-stimulatory properties only.

Nature of self-seeding polyethylene crystal nuclei

Abstract: In a limited temperature range above the clearing point of crystal suspensions, submicroscopic entities representing unmeasurably small portions of the original crystal population may survive whose existence is revealed by crystals nucleated on subsequent cooling [1]. Factors influencing the number of these nuclei and the nature of these nuclei themselves were explored in the case of polyethylene.

Comparison of the action of vantocil, cetrimide and chlorhexidine on Escherichia coli and its spheroplasts and the protoplasts of gram positive bacteria.

Abstract: SUMMARY The actions of chlorhexidine, cetrimide and Vantocil (the hydrochloride of a polymeric biguanide) on bacteria and spheroplasts or protoplasts derived therefrom have been compared. Lysis of Escherichia coli spheroplasts by chlorhexidine or cetrimide is due to rupture of the cytoplasmic membrane. Membranes ruptured with cetrimide can reform to give small, empty envelopes. With increasing concentrations of cetrimide or chlorhexidine more and more granules appear in the cytoplasm, increasing in size with increasing concentration, until the structure becomes transformed to a granular body similar in size to the original spheroplast. With chlorhexidine or Vantocil this now electron-dense body is rigid, but with cetrimide it collapses to a flat disc which does not lyse. The granules appear to consist of coagulated cytoplasm. This effect of excess of these antiseptics not only prevents osmotic lysis of the spheroplast or the collapsed disc but renders them immune to lysis by a variety of chemical agents. In isolated cytoplasm, chlorhexidine or cetrimide causes precipitation over a narrow range of concentrations but greater than those required for lysis. With Vantocil precipitation occurs gradually over a wide range of concentrations, starting at concentrations equal to those which cause a limited amount of lysis of the spheroplast or a relatively small increase in permeability of intact bacteria. Lanthanous and uranyl ions also precipitate cell contents but do not lyse spheroplasts; spheroplasts treated with these ions are protected from lysis by other agents.

The metabolism of 3,5-di-tert.-butyl-4-hydroxytoluene in the rat and in man.

Abstract: 1. The major metabolites of 3,5-di-tert.-butyl-4-hydroxytoluene (BHT) in the rat are 3,5-di-tert.-butyl-4-hydroxybenzoic acid (BHT-acid), both free (9% of the dose) and as a glucuronide (15%), and S-(3,5-di-tert.-butyl-4-hydroxybenzyl)-N-acetylcysteine. 2. The mercapturic acid does not appear to derive from the usually accepted enzyme mechanism, and may involve a non-enzymic reaction between BHT free radical and cysteine. 3. The ester glucuronide and mercapturic acid found in rat urine are also the major metabolites in rat bile and must be responsible for the enterohepatic circulation. 4. Free BHT-acid is the main component in rat faeces. 5. In man, BHT-acid, free and conjugated, is a minor component in urine, and the mercapturic acid is virtually absent. The bulk of the radioactivity is excreted as the ether-insoluble glucuronide of a metabolite in which the ring methyl group and one tert.-butyl methyl group are oxidized to carboxyl groups, and a methyl group on the other tert.-butyl group is also oxidized, probably to an aldehyde group. 6. These differences in metabolism by the rat and by man are sufficient to account for the difference in excretion by the two species.

A viscometric technique for determining the layer thickness of polymer adsorbed on titanium dioxide

Abstract: A simple viscometric method for measuring the adsorbed layer thickness of polymers on nonspherical particles is proposed. With the use of viscosities at infinite shear rate the effects of flocculation are eliminated and an empirical equation relating phase volume with viscosity is obtained. By use of this equation immobilized polymer thicknesses at the solid/liquid interface have been calculated and related to polymer structure.

The effect of psychotropic drugs on food reinforced behaviour and on food consumption.

Abstract: 1. Various measurements have been made of the change in food rewarded behaviour due to drugs. 2. Some sedatives enhance food rewarded behaviour in solitary rats. The Skinner box is a sensitive method of demonstrating this. 3. The evidence suggests that these sedatives act by controlling fear. 4. It is not possible using the Skinner box to say whether neuroleptics control fear because they have a basic anorexiant effect in laboratory animals.

Polymeric materials produced by interacting polyisocyanate and water in the presence of polyaldimine or polyketimine

Abstract: A PROCESS FOR THE MANUFACTURE OF SIOCYANATE-BASED POLYMERS WHICH COMPRISES INTERACTING AT LEAST ONE ORGANIC POLYISOCYANATE AND WATER IN THE PRESENCE OF A STERICALLY HINDERED BISALDIMINE OR BISKETIMINE DERIVED FROM AN AMINE CONTAINING TWO PRIMARY AMINO GROUPS. THE SOLUTIONS OF ISOCYANATES CONTAINING SUCH BISALDIMINES OR BISKETIMINES ARE SIGNIFICANTLY MORE STABLE THAN SIMILAR SOLUTIONS CONTAINING OTHER ALDIMINES OR KETIMINES. THIS INCREASED STABILITY IS OBTAINED WITHOUT ANY SIGNIFICANT DECREASE IN THE SPEED OF POLYMER FORMATION IN PRESENCE OF WATER OR LOSS OF DESIRABLE PROPERTIES IN THE POLYMERS, FOR EXAMPLE, SURFACE COATINGS, SO OBTAINED.

Mechanism of photostabilization of polypropylene by nickel oxime chelates

Abstract: Recent work has shown that certain nickel oxime chelates act as effective light stabilizers for polypropylene. The mechanism of their protective action was examined by spectrophosphorimetry and flash photolysis. Examination of the phosphorescence from the commercial polymer shows that it is due to aldehydic carbonyl groups. From flash photolysis observations of the triplet quenching action of a range of nickel chelates it is suggested that stabilization by the oxime chelates is achieved by a mechanism of efficient energy transfer from the photoreactive carbonyl group to the chelate, where the energy is harmlessly dissipated. The efficiency of this quenching action is primarily dependent on the spatial configuration of the ligand around the central metal atom in the chelate.

Aromatic polymers from dihalogenoben-zenoid compounds and alkali metal hydroxide

Abstract: AROMATIC POLYMERS CONTAINING BENZENOID GROUPS AND OXYGEN ATOMS IN THE POLYMER CHAINS ARE MADE BY THE ACTION OF AN ALKALI METAL HYDROXIDE ON A DIHALOGENOBENZENOID COMPOUND IN WHICH EACH HALOGEN ATOM IS ACTIVATED BY AN INERT ELECTRON-ATTRACTING GROUP SUCH AS -SO2-. WHEN A BIS-(4-HALOGENOPHENYL) SULPHONE IS REACTED WITH AN ALKALI METAL HYDROXIDE, THE ALKALI METAL SALT OF A 4-(4-HALOGENOPHENYLSULPHONYL) PHENOL IS FORMED AS A READILY ISOLATED INTERMEDIATE WHICH POLYMERISES IN THE PRESENCE OR SOLVENT TO GIVE A POLYMER HAVING REPEATING UNITS OF THE STRUCTURE -(1,4-PHENYLENE-SO2-1,4-PHENYLENE-O

Gel Permeation Chromatography of Polymers: Use of Unperturbed Dimensions for Calibration

Abstract: Experimental GPC calibration data for polystyrene, poly(methyl methacrylate), and poly(dimethyl siloxane) in chloroform is reported. These polymers have similar hydrodynamic volumes, since their unperturbed dimensions and extensions in chloroform, due to polymersolvent interaction, are very similar. As a result, the same molecular weight calibration curve is obtained for the three polymers. Recently published GPC data is examined on a plot of logarithm of unperturbed end-to-end distance against elution volume. This procedure gives a universal calibration for linear polymer molecules, providing the column combination, solvent, and temperature do not change. For the data of Meyerhoff, use of the unperturbed dimensions is superior to the plot of η suggested by Grubisic, Rempp, and Benoit. A possible explanation, based on a model for the polystyrene gel pores, is proposed for the use of the unperturbed dimensions.

The Crystal Structure of Anthranilic Acid

Abstract: The crystal structure of the form of anthranilic acid stable at room temperature has been determined from three-dimensional X -ray diffraction data. 1416 structure amplitudes were used in refining the positional and anisotropic thermal parameters, resulting in a discrepancy index R = 7.0% , and e. s. d. of 0.0045 A in the atomic coordinates. There are two non-equivalent molecules per lattice point in the space group P 2 1 cn , and the analysis shows these two molecules to have considerably different bond lengths. This evidence, taken together with the hydrogen-bonding system, indicates that one molecule is neutral, while the other is a zwitterion.

Influence of direct‐drilling of winter wheat on incidence of take‐all and eyespot

Abstract: SUMMARY Winter wheat drilled directly into stubble or pasture treated with paraquat to kill the vegetation has been found to be less severely attacked by take-all (Ophiobolus graminis (Sacc.) Sacc.) and eyespot (Cercosporella herpotrichoides Fron) than wheat drilled after cultivation. The reduction of take-all is associated, not with a direct effect of the chemical, but with factors, resulting from the technique, which limit the rate of spread of the fungus in the undisturbed soil.

Controlled crystal-growing procedures in polyethylene involving self-seeding: Some novel twinning habits

Abstract: The paper demonstrates the potentiality of the self-seeding technique [3] for the growing of single crystals of polyethylene. It is shown that with appropriate measures, uniform single-layer crystals of strictly controlled habit can be obtained. Concrete recipes are given for the growing technique. The habit features are systematized as functions of crystallization temperature and concentration. Novel twin formations with coincident centers arising from this work are described and analyzed. Their origin is correlated with the result suggested by an associated investigation that the nuclei have a multicomponent structure [4]. The advantages of the new crystal-growing technique for other lines of work are pointed out.

The inter-relation of some mechanical properties with molecular weight and crystallinity in poly(ethylene terephthalate)

Abstract: Some mechanical properties of poly(ethylene terephthalate) were determined as a function of molecular weight, temperature and crystallinity. The effect of talc, a nucleating agent, on mechanical properties was also considered.

Theory of Light Scattering in Amorphous Media

Abstract: (1968). Theory of Light Scattering in Amorphous Media. Optica Acta: International Journal of Optics: Vol. 15, No. 5, pp. 451-486.

Aqueous dispersion of block or graft polymer useful in surface modifying treatment of polyester shaped articles

Abstract: A STABLE DISPERSION IN WATER OF A BLOCK OR GRAFT COPOLYMER, A FIRST POLYMERIC CONSTITUENT OF WHICH IS A CRYSTALLINE POLYESTER AND A SECOND POLYMERIC CONSTITUENT OF WHICH IS SOLVATED BY WATER. THE FIRST POLYMERIC CONSTITUENT CONTAINS REPEAT UNITS OF THE TYPE USED IN FIBER-FORMING POLYESTER MATERIALS AND THE SECOND POLYMERIC CONSTITUENT PREFERABLY IS A POLYOXYETHYLENE CHAIN. THE DISPERSION IS USEFUL FOR APPLYING THE POLYMER TO THE SURFACE OF A POLYESTER ARTICLE TO PRODUCE A DURABLE SURFACE EFFECT.

Injection molding machines

Abstract: There is provided a method and apparatus for molding laminar articles. Two screw-injection barrels sequentially pass resinous materials through a valve in a single sprue into a mold cavity. The valve is controlled so that material from one screw-injection barrel does not pass while material flows from the other screwinjection barrel. The control means is synchronized so that the desired quantities of materials from the two injection barrels are placed in the mold cavity.

Plastics containers and packages

Abstract: Plastics film container for contents under superatmospheric pressure, closed by a bunched neck provided with a sealable material forming an internal gasket, and an external mechanical closure, and with a releasably sealed tube passing through the bunched neck.

Mechanism of Reaction of Proteins with Reactive Dyes:I‐Literature Survey

Abstract: The chemistry of reactive dyes and wool keratin is described briefly. Published investigations of the mechanisms of dyeing of wool and other protein fibres with reactive dyes are discussed and compared.

Tissue Homeostasis and the Biological Basis of Cancer

Abstract: Cell movement and cell division may share a common control mechanism Cell variation could account for its failure in malignancy