Showing papers by "Roussel Uclaf published in 1989"

A brief review of the environmental fate and metabolism of pyrethroids

Abstract: Pyrethroids are a class of lipophilic insecticide very easily degraded in the natural environment. The two main routes of degradation, photo- and biodegradation, are often superimposed. Pyrethroids developed for use in agriculture are much more photostable than the natural pyrethrins or early synthetic derivatives but they are still sensitive to sunlight, which triggers many alterations such as isomerisation or ester cleavage. The basic pathways of pyrethroid metabolism include hydrolysis of the central ester linkage and oxidation of both acid and alcohol moieties. The rate of these metabolic transformations and the nature of the metabolites depend mainly on the organism involved. Birds and mammals metabolise and excrete more rapidly than insects and fishes. In plants, initial metabolic processes are identical to those known in animals. In soil, pyrethroids undergo the same type of transformation, hydrolysis and oxidation. Neither degradation products nor intact parent compounds are leached.

Safety and tolerance of single oral doses of trandolapril (RU 44.570), a new angiotensin converting enzyme inhibitor.

Abstract: The safety and tolerance of single oral doses of a new angiotensin converting enzyme (ACE) inhibitor, trandolapril have been examined in 90 healthy male volunteers, in a randomised, double blind, placebo-controlled study. The subjects were divided into 10 groups, each of 9 subjects and treatments (6 subjects on trandolapril and 3 on placebo per group) were allocated by unbalanced randomisation. Ten single, increasing oral doses were tested: 0.125, 0.25, 0.5, 1, 2, 4, 8, 16, 24 and 32 mg. The assessment criteria were clinical (monitoring of blood pressure, heart and respiratory rate, electrocardiogram, temperature and evaluation of behaviour and side effects) and routine laboratory tests.

2,4-Dioxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine derivatives, process and intermediates for their preparation, their pharmaceutical use and compositions containing them

Abstract: The invention relates to the compounds of formula (I): … … in which:… - X and X', which may be identical or different, represent a hydrogen atom, a halogen atom or a cyano, NO2 or CF3 radical;… - R represents a hydrogen atom or an alkyl radical; and… - Ar represents an aryl radical, an aromatic heterocyclic radical or a heterocyclic radical fused to an aryl radical. … The compounds of formula (I) possess advantageous pharmacological properties which justify their use in therapy.

Protective effects of murine monoclonal antibodies in experimental septicemia: E. coli antibodies protect against different serotypes of E. coli.

Abstract: Murine monoclonal antibodies that bind outer membrane antigens of the J5 mutant of Escherichia coli O111:B4 were derived from spleen cells of BALB/c mice immunized with killed whole cells and boosted with lipopolysaccharide (LPS) and LPS-associated proteins. Seven hybridomas were selected for their reactivity against the J5 LPS; they cross-reacted with O111, O55, O127, and O128 E. coli LPS. One (B7B3) also reacted with the Serratia marcescens LPS and Klebsiella pneumoniae lipid A. A protective effect was obtained with D6B4 antibody in a lethal endotoxemia model induced by LPS from O111, O127, and O128 E. coli serotypes in D-galactosamine-sensitized mice. D6B4 and D6B3 antibodies protected mice infected with E. coli O111:B4, when administered before infection. The D6B4 antibody was also protective when administered after infection. The antibodies D6B3 and D4B5 were protective in heterologous infection induced by E. coli O2:K1.

9-alpha-hydroxy-17-methylene steroids, process for their preparation and their use in the preparation of corticosteroids

Abstract: New 9α-hydroxy-17-methylene steroids are prepared by the introduction of a substituted 17-methylene group in 9α-hydroxyandrost-4-ene-3, 17-dione The resulting compounds are useful starting compounds in the synthesis of corticosteroids

Angiotensin-converting enzyme in rat brain and extraneural tissues visualized by quantitative autoradiography using 3H-trandolaprilate.

Abstract: Tritium-labeled trandolaprilate (RU 44403), the active diacid form of the potent and long-acting angiotensin-converting enzyme (ACE) inhibitor trandolapril, has been evaluated as a new autoradiographic marker for the enzyme. The characteristics of 3H-trandolaprilate binding were first determined autoradiographically in tissue sections from rat brain (caudate-putamen) and kidney. 3H-Trandolaprilate binds saturably to these tissues, and with very high affinity (Kd values, 0.36 and 0.13 nM, respectively), and appears to show good selectivity for the enzyme. Due to its high affinity (approximately 100 times that of captopril), the performance of 3H-trandolaprilate as an autoradiographic marker is comparable to that of the recently described 125I-labeled derivative of lisinopril (125I-351A). Saturation and displacement studies in serial sections from a variety of central and peripheral tissues confirmed that the specificity of labeling was similar throughout. The anatomical distribution of ACE visualized with 3H-trandolaprilate in these tissues was close to that described for 3H-captopril and 125I-351A with some minor differences which might arise from difference in the specificity of the ligands.

Interferon-gamma (IFN-gamma) and interleukin-2 in the generation of lymphokine-activated killer cell cytotoxicity--IFN-gamma-induced suppressive activity.

Abstract: Incubation of human lymphocytes with recombinant interleukin-2 (rIL-2) results in the generation of lymphokine-activated killer (LAK) cells capable of lysing a wide variety of tumor cells. The present study was undertaken to examine the effect of recombinant gamma interferon (rIFN-gamma) on LAK cell cytotoxicity generated from different peripheral blood mononuclear cell (PBMC) subpopulations. When unseparated PBMC were stimulated by rIL-2 and rIFN-gamma, the latter induced a transient enhancement after 2 days followed by a suppression of LAK cell cytotoxicity at day 6. Enhancement of LAK cell cytotoxicity was moderate and inconstant, whereas the inhibition was strong and observed with all the donors tested. This suppression was not associated with a decrease in the [3H]thymidine uptake. PBMC depleted of adherent cells were more sensitive to the stimulation by rIL-2 and the induced cytotoxicity was not modified by rIFN-gamma. Monocyte-enriched plastic-adherent cells, when incubated with rIL-2 and rIFN-gamma, became cytotoxic after 2-3 days of culture and inhibited LAK cell activity after 5-6 days. Collectively, our results suggest that rIFN-gamma affects LAK cell cytotoxicity through the activation of plastic-adherent, monocyte-rich, cells which modulate natural killer cells, first in a positive, then in a negative way.

Novel cyclopropane carboxylates

Abstract: Novel 2,2-dimethyl-cyclopropane carboxylic acid derivatives of the formula ##STR1## wherein X 1 and X 2 are individually halogen, R 1 is selected from the group consisting of halogen, alkyl of 1 to 8 carbon atoms, optionally substituted aryl of 6 to 14 carbon atoms, perfluoroalkyl of 1 to 8 carbon atoms, --CN and ##STR2## R' is alkyl of 1 to 8 carbon atoms, Y is selected from the group consisting of --SO 2 Alk 1 , --SO 2 Ar, ##STR3## Alk 1 is optionally unsaturated alkyl of 1 to 8 carbon atoms no substituted or substituted with at least one functional group, Ar is aryl of 6 to 14 carbon atoms no substituted or substituted with at least one functional group, Alk 2 and Alk 3 and Alk 2 ' and Alk 3 ' are optionally unsaturated alkyl of 1 to 8 carbon atoms no substituted or substituted with at least one functional group or together with ##STR4## form the rings ##STR5## wherein A is optionally unsaturated alkyl of 1 to 6 carbon atoms optionally substituted with at least one functional group, R" is alkyl of 1 to 6 carbon atoms no substituted or substituted with at least one functional group or aryl of 6 to 14 carbon atoms no substituted or substituted with at least one functional group and R is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms and residue of an alcohol used in pyrethrinoid esters having pesticidal activity

Cosmetic compositions for combating cellulitis

Abstract: The cosmetic compositions are characterised in that they contain as active substances acid mucopolysaccharides extracted from connective tissues of animals, together with a cola seed extract.

Monoclonal antibodies to human interleukin-1 beta and their use in a sensitive two-site enzyme linked immunosorbent assay.

Abstract: Five Monoclonal Antibodies (MAbs) coded respectively #111, 122, 206, 209 and 609 were produced against human recombinant Interleukin-1 beta (rIL-1 beta, amino acids 117-269). Four of these MAbs (#111, 122, 206 and 609) have been identified able to inhibit the biological activity of recombinant and natural Interleukin-1 beta. Competition studies suggested that three non-overlapping epitopes of the molecule were recognized by the MAbs. MAbs #609 and 206 have been selected on the basis of high affinity and used together in a two-site ELISA to detect IL-1 beta. The sensitivity of this ELISA was 1 pg/well (10-20 pg/ml). The assay did not detect rHuIL-1 alpha, rHuIL-2, rHuTNF-alpha, rHuIFN-gamma, rHuIL-6, and natural a- and b-FGF. The immunoassay was then compared to current assay such as co-mitogenic effect on murine thymocytes for detection of IL-1 beta in the intra- and extracellular compartments of IFN-gamma and/or LPS-stimulated human blood monocytes. We confirm that IFN-gamma potentiates IL-1 beta secretion in response to LPS (even with high dose 1 microgram/ml) but not the intracellular precursor of IL-1 beta. This immunoassay could be used also to detect IL-1 beta in plasma, sera and synovial fluids.

Compounds of 1,2,5,6-tetrahydropyridine which are useful as cholinergic agents

Abstract: Compounds useful in the treatment of Alzheimer's disease, senile dimentia and memory disorders of the formula ##STR1## in which R represents hydrogen, hydroxyl, a linear, branched or cyclic, saturated or unsaturated, alkyl, containing up to 8 carbon atoms, possibly substituted by free or esterified carboxy or R represents aralkyl containing up to 10 carbon atoms or --COOZ in which Z represents a linear, branched or cyclic saturated or unsaturated, alkyl containing up to 8 carbon atoms and R2 represents hydrogen or a linear or branched, saturated or unsaturated alkyl containing up to 8 carbon atoms, COalk1 radical or (CH2)2 N(alk2)2, alk1 and alk2 representing an alkyl containing up to 8 carbon atoms, as well as their addition salts with acids provided that if R represents an alkyl R2 does not represent hydrogen; also therapeutic compositions containing at least one said compound and method of treating patients with said compounds.

Derivatives of 1,2,5,6-tetrahydropyridine substituted by a thiazolyl or oxazolyl radical, their use as medicaments and compositions containing them

Abstract: Compounds of formula (I) ##STR1## in which X represents oxygen or sulphur, R1 represents hydrogen, a linear, branched or cyclic alkyl containing up to 8 carbon atoms, an alkenyl or alkynyl containing up to 6 carbon atoms, hydroxyl, an OCOalk1 radical in which alk1 represents alkyl containing up to 6 carbon atoms, an OCONHalk2 radical in which alk2 represents alkyl containing up to 6 carbon atoms, a CO2 alk3 radical in which alk3 represents alkyl or alkenyl containing up to 6 carbon atoms, an Oalk4 radical in which alk4 represents alkyl containing up to 6 carbon atoms, an OCOAr1, OCONHAr2 or CO2 Ar3 radical in which Ar1, Ar2 or Ar3 represents aryl containing up to 14 carbon atoms, R2 represents hydrogen, a linear, branched or cyclic alkyl containing up to 6 carbon atoms, alkenyl or alkynyl containing up to 6 carbon atoms, an alkoxyalkyl alk'1 Oalk'2 radical in which alk'1 and alk'2 represent alkyl containing up to 6 carabon atoms, hydroxyalkyl in which the alkyl contains up to 6 carbon atoms or aryl containing up to 14 carbon atoms, as well as their addition salts with organic or mineral acids, which compounds are useful in the treatment of patients suffering from Alzheimer's disease, senile dementia or memory disorders of the aged; also, compositions containing the same, method of use, method of preparation, and intermediates therefor.

1-azabicycloalkane derivatives, their preparation process and their use as medicaments

Abstract: Compounds useful in the treatment of Alzheimers's disease, senile dementia or memory disorders of the aged of the formula ##STR1## in which n represents the number 1, 2 or 3, R1 and R2, identical or different, represent hydrogen, a linear, branched or cyclic alkyl, alkenyl, or alkynyl which contain up to 6 carbon atoms, R1 and R2 optionally substituted by hydroxy, alkoxy containing up to 6 carbon atoms, aralkyl containing up to 14 carbon atoms, a COOalk1 radical in which alk1 represents alkyl containing up to 6 carbon atoms, a --CON(alk2)2 radical in which alk2 represents alkyl containing up to 6 carbon the radical --C(R1)═NOR2 being in position 2, 3 or 4, in all their isomer forms and their mixture, as well as their addition salts with pharmaceutically acceptable organic or mineral acids. Also therapeutic compositions containing the compounds, method of treatment and method of preparation.

Novel 3-acetoxymethyl-7-(iminoacetamido)-cephalosporanic acid derivatives

Abstract: Compounds of the formula ##STR1## wherein R is selected from the group consisting of hydrogen and groups easily removable by acid hydrolysis of hydrogenolysis, R' is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, alkenyl and alkynyl of 2 to 4 carbon atoms and groups easily removable by acid hydrolysis or hydrogenolysis. A is selected from the group consisting of hydrogen, alkali metal and equivalents of an alkaline earth metal or magnesium and an organic amine base with the proviso that when R' is a group easily removable by acid hydrolysis of hydrogenolysis, R is also and when R' is hydrogen, R also is hydrogen and the wavy line means the OR' group may be in either one of the two possible syn or anti positions having antibiotic activity and process for their preparation.

Fluor derivatives of 3-ethenyl-2,2-dimethyl cyclopropane-carboxylic acid, method for their preparation, their use as pesticides and compositions containing them

Abstract: Compounds of formula (I): in all the possible stereoisomeric forms and mixtures of these stereoisomers, in which: - Hal1 and Hal2, which are different from each other, denote a fluorine, chlorine, bromine or iodine atom, - Z denotes a hydrogen atom or a CH3, C IDENTICAL N or C IDENTICAL CH radical, - n denotes an integer which can be from 1 to 5, - m denotes the number 5-n, and - Y denotes a hydrogen or halogen atom, a radical CH2-CN, a hydroxyl, an optionally substituted C1-8 alkyl, nitrile, C(=O)-Oalkyl, C(=O)- alkyl, (CH2)m'O-alkyl, (CH2)m'S-alkyl, (CH2)mN-(alkyl)2 (C1-12), m' denoting 0, 1, 2, 3 or 4, an Si(alkyl)3 radical, alkyl denoting an optionally substituted C1-8 alkyl, O-aryl or -(CH2)m'-aryl, aryl denoting a C6-14 aryl, it being possible for the substituent(s) Y, which may be identical or different, to be in any position on the phenyl nucleus, process for their preparation, their application as pesticides and the compositions containing them.