Showing papers by "Novartis published in 1981"

Characterization and Function of T Cell Fcgamma Receptor

Abstract: Soon after their discovery, receptors for the Fc fragment of immunoglobulins (FcR) were envisaged as key molecules regulating immune reactions, since they allow for interaction between immunocompetent cells and antibodies (reviewed by Dickler 1976). In fact, evidence increasingly in favors such receptors being expressed on subsets of all cell types that compose the immune system (Basten et al. 1972a, Yoshida & Andersson 1972. Unkeless & Fisen 1975) and that FcR exist for all immunoglobulin classes (Dickler & Kunkel 1972, Moretta et al. 1975, Gonzalez-Molina et al. 1977, Gupta et al. 1979) and for some subclasses (Basten et al. 1972b, Anderson & Grey 1974, Krammer et al. 1975, Walker 1976, Heusser et al. 1977, Unkeless 1977, Haeffner-Cavaillon et al. 1979). Thus, maerophages (Unkeless & Fisen 1975, Heusser et al. 1977), B cells (Basten et al. 1972a, Dickler & Kunkel 1972), K cells (MacLennan 1972, Perlmann et al. 1972), some T cells (Yoshida & Andersson 1972, Fridman & Golstein 1974, Van Boxel & Rosenstreich 1974, Soteriades-Vlachos et al. 1974) and NK cells (Peter et al. 1975, Herberman et al. 1979) express FeR for IgG (FcyR)A subset of human (Moretta et al. 1975) and possibly also murine (Lamon et al. 1975) T cells bear FcR for IgM (Fc)iR) and the existence of a similar receptor on activated maerophages has also been suggested (Roubin et al. 1979). Finally, some T cells have been found to express FcR for IgA (Gupta et al. 1979, Lumetal. 1979) and IgF (FCER; Yodoi & Ishizaka 1979).

Reversed-phase chromatography as a general method for determining octan-1-ol/water partition coefficients

Abstract: Reversed-phase high-pressure liquid chromatography (h. p. l. c.) and thin-layer chromatography (t. l. c.), on commercially available, reversed stationary phases, were used to determine the octan-1-ol/water partition coefficients (P) for 20 non-ionic organic chemicals, consisting mainly of known pesticides in common use. Good correlation was found between log P values and both the logarithms of the capacity factor (k′), obtained by h. p. l. c., and the Rm values derived from t. l. c. The methods were found to be applicable over a range of more than six orders of magnitude in P values. In addition, the relation is shown between the P values of organic chemicals and their solubilities in water and in octan-1-01.

Mixtures of polymeric high-molecular acrylic quaternary ammonium salts and detergents, their preparation and use in cosmetic formulations

Abstract: Gemische, die Mixtures (a) in wasrigen Tensidsystemen losliche oder mikroemulgierbare, polymere Ammoniumsalze, die durch Wasser-in-OI-Emulsionspolymerisation oder Losungspolymerisation eines quaternaren Ammoniumsalzes der Acrylsaurereihe und gegebenenfalls mindestens eines weiteren Monomeren auf Acrylbasis erhaltlich sind und die eine Molekulargewichtsverteilung von 10 4 bis 10 9 aufweisen, wobei das Molekulargewicht von mindestens 5 Gewichtsprozent des Polymerisats 10 7 bis 10 9 betragt, und (b) ein nicht-ionisches Tensid oder ein Tensid mit intramolekular je einer positiven und negativen Ladung enthalten, sind als kosmetische Mittel, insbesondere als Haarkosmetika verwendbar, wobei das erfindungsgemas behandelte Haar eine ausgezeichnete Trocken- und vor allem Naskammbarkeit aufweist. (a) soluble in aqueous surfactant systems or microemulsifiable, polymeric ammonium salts, the acrylic-based are obtainable by water-in-oil emulsion polymerisation or solution polymerisation of a quaternary ammonium salt of the acrylic acid series and optionally at least one further monomer and having a molecular weight distribution of 10 4 to 10 9 wherein the molecular weight of at least 5 weight percent of the polymer 10 7 to 10 9, and (b) a non-ionic surfactant or a surfactant having intramolecularly each containing a positive and negative charge are as cosmetic agent, in particular as hair cosmetics can be used, wherein the hair treated according exhibiting excellent dry and especially wet combability.

Further evidence for negative feedback control of serotonin release in the central nervous system.

Abstract: In the presence of the serotonin (5-HT) uptake inhibitor citalopram (2×10−5 M), 5-HT, added to the superfusion medium, diminished the electrically induced 3H-overflow from rat cortex slices prelabelled with 3H-5-HT. A 50% decrease of the 3H-overflow was obtained with 6×10−7 M 5-HT. Of the 5-HT antagonists tested (methysergide, methergoline, methiothepin, cyproheptadine, cinanserin, mianserin, pizotifen), methiothepin (50% at 4.5×10−7 M), methergoline (31% at 10−6 M) and cinanserin (30% at 10−6 M) increased the stimulation-induced 3H-overflow. In some experiments the overflow of endogenous 5-HT was measured simultancously with 3H-overflow. The results were qualitatively and quantitatively very similar, indicating that 3H-overflow can be taken as a reliable measure of 5-HT release. The existence of a functional negative feedback control of 5-HT release mediated by presynaptic autoreceptors was confirmed by analysis of the 3H-overflow per pulse at stimulation frequencies between 0.1 and 50 pulses per second (pps). The 3H-overflow per pulse decreased with increasing stimulus frequency, reaching a low level at 1.6 pps corresponding to 30% of the initial value at 0.1 pps. Methiothepin did not increase the stimulation-induced 3H-overflow at 0.1 pps. The stimulation-induced 5H-overflow at 0.1 pps in the absence of methiothepin was equivalent to that at 1.6 pps in the presence of methiothepin. These results suggest that, under the given experimental conditions, at a stimulation frequency of 0.1 pps the 5-HT concentration in the synaptic cleft drops to very low levels, barely sufficient to induce negative feedback. Among a variety of drugs tested, LSD, dimethyltryptamine, m-chlorophenylpiperazine and clonidine decreased the stimulation-induced 3H-overflow, whereas salbutamol, propranolol, oxprenolol, spiroperidol and haloperidol had no effect. Quipazine, known as a 5-HT agonist, unexpectedly augmented the stimulation-induced 3H-overflow. This effect might be attributable partly to its 5-HT uptake inhibiting component, and also to blockade of presynaptic 5-HT receptors.

Stabilizer systems of triarylphosphites and phenols

Abstract: Use of symmetrical triarylphosphites of the general formula I ##STR1## wherein R1 is tert.-butyl, 1,1-dimethylpropyl, cyclohexyl or phenyl, and one of R2 and R3 is hydrogen and the other is hydrogen, methyl, tert.-butyl, 1,1-dimethylpropyl, cyclohexyl or phenyl, in combination with phenolic antioxidants for stabilizing organic polymers which contain hetero atoms, double bonds or aromatic rings.

Perfluoroalkyl anion/perfluoroalkyl cation ion pair complexes

Abstract: The instant invention relates to the use of ion-pair complexes derived from anionic perfluoroalkyl sulfonates, carboxylates, phosphates and phosphonates and cationic perfluoroalkyl surfactants. Such complexes are capable of reducing the surface tension of aqueous solutions dramatically even at extremely low concentrations, and are useful as wetting, spreading and leveling agents and are especially preferred as components in so-called aqueous film forming foam compositions for fighting polar and non-polar solvent and fuel fires.

Chemical hydrolysis of 2-chloro-4,6-bis(alkylamino)-1,3,5-triazine herbicides and their breakdown in soil under the influence of adsorption†

Abstract: The determination of rate constants and the calculation of the activation parameters [activation energy (Ea), free energy of activation(ΔG≠)and entropy of activation (ΔS≠)] demonstrated the identity of the reaction kinetics of chemical hydrolysis of the chlorinated triazine herbicides simazine, atrazine, propazine and terbuthylazine. Persistence in soil could be estimated, from the hydrolytic half-life time, only in pH regions where these compounds were also sensitive to chemical hydrolysis. In general, the rate of hydrolysis increased in the presence of soil as the result of a catalysing effect of the soil in their breakdown. When half-lives in soil of these triazine herbicides were compared with adsorption constants, a functional relationship was observed in both soil types; as adsorption increased the half-life in soil also increased.

Pyridoxine megavitaminosis produces degeneration of peripheral sensory neurons (sensory neuronopathy) in the dog.

Abstract: Pyridoxine, a water-soluble vitamin, produces a sensory neuronopathy when administered in high doses to dogs Beagles who received a daily oral dose of 300 mg/kg of pyridoxol hydrochloride developed a swaying gait within 9 days They eventually became unable to walk, but were not weak Animals were sacrificed at intervals up to 78 days Morphological examination revealed widespread neuronal degeneration in the dorsal root ganglia and the Gasserian ganglia Cytoplasmic changes were first observed after 8 days and consisted of small, electronlucent vacuoles that subsequently coalesced leading to death of the cells Degeneration of sensory nerve fibers in peripheral nerves, dorsal columns of the spinal cord and the descending spinal tract of the trigeminal nerve was apparent The pathogenesis of these changes is unclear, but may, in part, reflect the selective permeability of blood vessels in the peripheral ganglia It is apparent that the peripheral neuropathy previously attributed to pyridoxine actually represents a toxic, peripheral sensory neuronopathy

3-Methoxytyramine: its suitability as an indicator of synaptic dopamine release.

Abstract: The value of 3-methoxytyramine (3-MT) as an indicator of impulse-related dopamine (DA) release has been assessed in rat corpus striatum. Moreover, the turnover of 3-MT was estimated by measuring its disappearance rate after COMT inhibition. Quantitation of 3-MT and DA was performed by gas chromatography/mass spectrometry (selected ion monitoring). Haloperidol in doses between 0.05 and 3 mg/kg p.o. did not increase endogenous 3-MT levels at any time up to 24 h after its administration, whereas it dose-dependently increased homovanillic acid and 3,4-dihydroxyphenylacetic acid. However, in doses above 0.1 mg/kg p.o., it enhanced the accumulation of 3-MT in clorgyline-pretreated animals. Conversely, baclofen in doses of 2 mg/kg i.p. and above decreased endogeneous 3-MT levels, but reduced the accumulation of this amine only poorly at 20 mg/kg i.p. in clorgyline-pretreated rats. A number of dopamine agonists, apomorphine (0.5 mg/kg i.v.), dipropyl-ADTN (0.03 mg/kg i.v.), but not bromocriptine (1 mg/kg i.v.) reduced endogenous 3-MT levels 10 min after administration by approximately 50%. The DA releasing agents d-amphetamine and methylphenidate showed different effects: the former increased endogenous 3-MT greatly, whereas the latter was without effect. The difference is likely to be related to the MAO inhibitory properties of amphetamine. 3-MT disappeared rapidly after COMT inhibition with 50 mg/kg i.v. tropolone (half-life of the initial disappearance about 1 min). The curve flattened off after 5–10 min. Turnover was calculated to be about 7 nmol/g/h, which corresponds to about a third of the turnover of DA. Our results suggest that an important part of DA metabolism occurs through 3-MT and that this amine is very effectively deaminated by MAO-A, so effectively indeed that increased formation does not increase its endogeneous levels. It appears, therefore, that 3-MT is not suitable as an indicator of increased DA release. However, it seems to have some value for an assessment of lowered DA release.

Interaction of beta-adrenoceptor agonists with the serotonergic system in rat brain. A behavioral study using the L-5-HTP syndrome.

Abstract: The effect of β-adrenoceptor agonists on the behavioral effect of l-5-HTP in rats and mice was studied. All β-agonists potentiated the behavioral syndrome elicited by l-5-HTP. However no indication for a correlation between their potencies to stimulate peripheral beta-receptors and their potencies to enhance l-5-HTP effects was found. The potentiating effect of salbutamol in rats was intensified by the MAO A inhibitor clorgyline, completely inhibited by (±)-propranolol and partly inhibited by WB-4101, while practolol was without effect. Lesions of 5-HT pathways by i.c.v. injections of 5,7-DHT impaired the potentiating effect of salbutamol in rats. In contrast, 6-OHDA lesions or alphamethyl-p-tyrosine pretreatment were without effect. A central site of action of salbutamol is suggested by the fact that it intensified l-5-HTP effects also after i.c.v. administration. Therefore the results suggest that salbutamol facilitates 5-HT transmission in rat brain probably via stimulation of central beta receptors.

Daylength and breeding in the domestic cat

Abstract: A period of extended daylight (more than 12 hours per day) following one of short days induces oestrus. The longer the short-day period, the more pronounced the reaction. This change from short-day to long-day periods can be successfully repeated at least 6 times in a year. However, the number of litters produced per year is largest when a regular 12 h light/dark cycle is maintained.

Process for the preparation of alkenylbenzenecarboxylic acid derivatives and alkenylnaphthalenecarboxylic acid derivatives

Abstract: Compounds of the formula I ##STR1## in which p, m, Z, R, R' and Y are as defined in claim 1, can be obtained in a simple and economical manner by a novel process which comprises reacting a halide of the formula ##STR2## with the corresponding acrylic acid derivative, in the presence of a base and of certain palladium catalysts, such as palladium acetate. The compounds (I), and functional derivatives prepared therefrom, are useful for the preparation of photocrosslinkable polymers, which can in particular be employed as (so-called) photoresists.

1-Carboxyalkanoylindoline-2-carboxylic acids

Abstract: 1-Carboxy-(alkanoyl or aralkanoyl)-indoline-2-carboxylic acids, e.g., those of the formula ##STR1## R=H, alkyl, alkoxy, halogeno or CF 3 ; R'=H or R-phenyl; m=0 or 1; p,q=0 to 2; and functional derivatives thereof, are antihypertensive and cardioactive agents.

Inorganic sulfur as a fungicide

Abstract: Elemental sulfur is undoubtedly the oldest of all pesticides. Much of the early history of this pesticide is lost, but its pesticidal properties were known by the ancient Greeks as early as 1000 B.C. FORSYTH (1802) first recorded the recommendation of sulfur for the control of diseases. His recommendation for the control of powdery mildew on fruit trees was a concoction of quicklime, sulfur, elderberry bud, and tobacco. ROBERTSON (1824) reported at the London Horticultural Society that sulfur was the only effective remedy that he knew for the control of mildew on peaches. He recommended the addition of soap to augment disease control; thus the use of surfactants to enhance pesticidal properties is not a modern innovation. ROBERTSON further emphasized the importance of complete coverage for improved disease control. Later MEARNS (1835) recommended that sulfur be mixed with soft soap and barnyard manure for the control of mildew on roses. In 1841, MEARNS recommended a mixture of alcohol and sulfur for the control of powdery mildew on peaches. He recognized the importance of early applications and stated that the mixture should be painted on the branches during dormancy in early spring.

The sensitivity of cortical neurons to serotonin: effect of chronic treatment with antidepressants, serotonin-uptake inhibitors and monoamine-oxidase-blocking drugs.

Abstract: The sensitivity of rostral and cingulate cortical neurons to microiontophoretically administered serotonin (5-HT) was compared in groups of rats treated either acutely or chronically for different periods with various drugs. The drugs used were: desipramine (10 mg/kg), clomipramine (10 mg/kg), CGP 6085 (10 mg/kg), clorgyline (0.3 mg/kg), and deprenyl (1 mg/kg). Serotonin and, in some instances, gamma-aminobutyric acid (GABA) were applied microiontophoretically over periods of 60 sec with various ejection currents to spontaneously active neurons in the rostral and cingulate cortex. Of all the compounds tested, only clorgyline produced a marked desensitization to 5-HT in both cortical areas. After prolonged treatment with all the other drugs, no change in the sensitivity to serotonin was observed. The desensitization to 5-HT induced by clorgyline developed after 4 to 10 days of treatment. The responsiveness of these cells to GABA was unchanged after chronic exposure to clorgyline. The present results are consistent with those biochemical studies showing that chronic treatment with 5-HT-uptake-blocking compounds has no effect on 5-HT-binding characteristics, as well as with the observation that prolonged treatment with the monoamine-oxidase A-type blocker clorgyline reduces the number of 5-HT-binding sites.

Triazine carboxylic acids as corrosion inhibitors for aqueous systems

Abstract: Triazine di- and tricarboxylic acids of the formula ##STR1## wherein Z is a straight-chain or branched chain unsubstituted or substituted 1-11C alkylene group, a 2 or 3C alkenylene group, a 5-12C cycloalkylene group or an unsubstituted or substituted arylene group, X is H, an alkali metal, an alkaline earth metal, NH 4 + or a primary, secondary or tertiary 1-12C ammonium residue, R 1 and R 2 are the same or different and each is H, 1-4C alkyl or a group --Z--COOX or R 1 or R 2 together with Z can form a 5- or 6-membered heterocyclic ring, R 3 is 1-12C alkyl, phenyl or a group of formula --NR 4 R 5 , --OR 6 or --SR 6 in which R 4 and R 5 , independently, are H, 1-12C alkyl optionally substituted by a hydroxyl group, cyclohexyl, an aryl group having from 6 to 10 ring carbon atoms, optionally substituted or a group --Z--COOX and R 6 is H, 1-12C alkyl, or a 6-12C aryl group, are excellent corrosion inhibitors for aqueous systems in contact with ferrous metals. Such systems may be e.g. water circuits, aqueous machining fluids or any other aqueous functional fluids.

Rate of volatilisation of pesticides from soil surfaces; comparison of calculated results with those determined in a laboratory model system

Abstract: A laboratory model system for the determination of the volatility of non-ionic pesticides from soil surfaces is presented. The pesticides examined were the insecticides methidathion, diazinon, and isazophos, the herbicide metolachlor, and the fungicide metalaxyl. The rates of volatilisation of these compounds from soil increased with increasing pesticide concentration, temperature and air flow rate and with decreasing soil organic matter content. The volatilities of the same pesticides were also calculated by using their vapour pressure, water solubility and soil adsorption data. The excellent correlation between calculated and experimental results showed that information on the volatility of a chemical can be obtained simply by calculation. Such calculations allow the classification of each pesticide according to its volatility, and therefore represent a useful alternative for volatility studies in laboratory model systems.

Phenylpyrimidines as antidotes for protecting cultivated plants against phytotoxic damage caused by herbicides

Abstract: Phenylpyrimidines of the formula I as defined below are suitable as antidotes for protecting cultivated plants from phytotoxic effects caused by herbicides. These antidotes, either together with the herbicides or also by themselves, are applied to the plants or incorporated in the soil in which the plants grow, or they are used to treat the seeds of the plants. Suitable herbicides are those belonging to the class of the haloacetanilides, haloacetamides, thiocarbamates, carbamates, nitroanilides, triazines, phenylureas, haloacetic acids, phenoxy- and pyridyloxyphenoxyalkanecarboxylic acid derivatives, benzoic acid derivatives etc. The phenylpyrimidines have the formula I ##STR1## wherein n is an integer from 1 to 5, R is hydrogen, halogen, cyano, nitro or hydroxyl, a C1 -C6 -alkyl, C1 -C6 alkoxy or C1 -C6 alkylthio group, which is unsubstituted or mono- or polysubstituted by halogen, C1 -C6 alkoxy, C2 -C12 alkoxyalkyl, C1 -C6 alkylcarbonyl, C1 -C6 alkylcarbonyloxy, C1 -C6 alkoxycarbonyl, C2 -C6 alkenylcarbonyl or C2 -C6 alkynylcarbonyl, di(C1 -C6)alkylamino, C1 -C6 alkylenedioxy, phosphonyl or C1 -C6 alkylphosphonyl; or R is a C2 -C6 alkenyl or C2 -C6 alkenyloxy group or the formyl or carboxyl group; or is a carbonyl or carbonyloxy group which is substituted by C1 -C6 alkyl, C1 -C6 haloalkyl, C1 -C6 alkoxy, C2 -C6 alkenyl, C2 -C6 alkynyl, amino, di(C1 -C6)alkylamino, or by a 5- to 6-membered saturated heterocyclic ring which is bound through the nitrogen atom; or is an amino group which is unsubstituted or substituted by C1 -C6 alkyl, C1 -C6 alkoxy or C1 -C6 alkylcarbonyl; or it is an ureido radical which is unsubstituted or substituted by C1 -C6 alkyl or C1 -C6 alkoxy or it is the sulfonyl, a C1 -C6 alkylsulfonyl, the sulfamoyl, a C1 -C6 alkylsulfamoyl or a C1 -C6 alkylcarbonylsulfamoylrest, R1 and R3 each independently of the other is halogen, cyano, hydroxyl, sulfhydryl, a C1 -C6 alkyl, C1 -C6 alkoxy or C1 -C6 ethylthio radical, which is unsubstituted or substituted by halogen or C1 -C6 alkoxy; a C2 C6 alkenyl or C2 -C6 alkynyl radical, a C3 -C6 cycloalkyl radical, an amino, C1 -C6 alkylamino or di(C1 -C6 alkyl) amino, group, a 5- to 6-membered saturated heterocyclic ring, which is bound through the nitrogen atom, a phenyl or phenoxyrest and R2 is hydrogen, halogen, C1 -C6 alkyl, C1 -C6 haloalkyl or phenyl.

Photopolymerization by means of sulphoxonium salts

Abstract: Substances (I) capable of being converted into higher-molecular weight materials under the influence of a cationic catalyst, such as 1,2-epoxides, aminoplasts, vinyl monomers or prepolymers, or phenoplasts, are so converted by exposure to actinic radiation in the presence of a sulphoxonium salt (II) of formula ##STR1## where P denotes zero or 1, R6 denotes an arylene or aralkylene group, R7 denotes --H or a group of formula ##STR2## R8 denotes an alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl group, R9 has the same meaning as R8 but may alternatively represent a dialkylamino group or, if R8 represents an alkyl group, R9 may represent an arylamino group, R10 and R11 each independently have the same meaning as R8 but may also each denote --H, r represents 1, 2, or 3, Zr- denotes an r-valent anion of a protic acid, and q denotes zero when p denotes zero, or zero or 1 when p denotes 1. Typical II are dimethylphenylsulphoxonium hexafluorophosphate and perchlorate, dimethylphenacylsulphoxonium hexafluorophosphate, and chloride, dodecylmethylbenzylsulphoxonium hexafluorophosphate, and 1,4-bis(1-oxo-2-(dimethylsulphoxonium)ethyl)benzene dihexafluoroarsenate. When I is a polyepoxide or a resol, it may be photopolymerized by means of II and subsequently crosslinked by heating with a latent heat-curing agent.

Stimulation of central serotonin turnover by β-adrenoceptor agonists

Abstract: The β2-stimulators salbutamol (0.3–30 mg/kg i.v.) and clenbuterol (0.3 and 1 mg/kg i.v.), and, to a lesser extent, the β1-stimulators dobutamine (30 mg/kg i.v.) and prenalterol (30 mg/kg i.v.) increased serotonin metabolism in several rat brain areas, as indicated by increased concentrations of 5-hydroxyindoleacetic acid (5-HIAA) or increased tryptophan hydroxylation in vivo. With salbutamol, increases in 5-HIAA in c. striatum and brainstem, but not in cortex, were observed after intraventricular administration of relatively low doses (3–30 μg). Direct application of the compound into the dorsal raphe nucleus at doses of 100 ng and 1 μg were without effect, and only mininal 5-HIAA increases occurred after the high dose of 10 μg. The effects of salbutamol on the concentrations of 5-HIAA were antagonized by both propranolol and WB4101, indicating an involvement not only of β-receptors but also of postsynaptic α-receptors. The evidence for and against a central site of action of β-agonists with respect to their effect on serotonergic systems is discussed.

Process for the preparation of alkenylbenzene derivatives or alkenylnaphthalene derivatives

Abstract: Compounds of the formula I (I) in which Z, Z1, R, m and p are as defined in patent claim 1, can be obtained in a simple and economical manner by a novel process wherein a halide of the formula II (II) is reacted with a substituted or unsubstituted vinylbenz-ene or vinylnaphthalene derivative in the presence of a base and of certain palladium catalysts, such as palladium acetate, The compounds (I) or functional derivatives preparable therefrom are useful. for example, for the preparation of known dyes or fluorescent brighteners, or can be used directly as fluorescent brighteners or as scintillators.