Showing papers by "Roussel Uclaf published in 1986"

Analysis of the nucleotide sequence of the ereB gene encoding the erythromycin esterase type II.

Abstract: We have determined the nucleotide sequence of the ereB gene of plasmid pIP1527 which confers high-level resistance to erythromycin by inactivation in Escherichia coli. The open reading frame of the ereB gene, 1257-bp, was defined by initiation and termination codons and by cloning in vitro. The corresponding protein has a calculated Mr of 48,118 in close agreement with a previous estimation, 51,000, by electrophoresis of minicell extracts in SDS-polyacrylamide gels. The structure of the modified erythromycin was determined by physico-chemical techniques including mass spectrometry, infrared spectrophotometry and 13C nuclear magnetic resonance. The data obtained indicated that like ereA (Ounissi and Courvalin, 1985) ereB encodes an erythromycin esterase. Comparison of the amino acid sequences of the two isozymes did not reveal any statistically significant homology. Analysis of the nucleotide sequence of the ereB gene suggests that this resistance determinant should be exogenous to E. coli.

Antibacterial activity of roxithromycin: a laboratory evaluation

Abstract: Roxithromycin, formerly known as RU 28965 (9-[O [(2-methoxyethoxy)methyl]oxime]-erythromycin), is a novel 14 atom-membered semisynthetic macrolide with an antibacterial spectrum directed towards Gram-positive cocci and bacilli, Gram-negative cocci and some Parvobacteriaceae. The in vitro antibacterial activity of roxithromycin was compared with those of erythromycin and spiramycin against 275 clinical isolates by using 2-fold broth macro-dilution tests. The antibacterial spectrum of roxithromycin and erythromycin were qualitatively comparable (including the bacteriostatic type of activity and the profile of resistance), but minimal inhibitory concentrations of erythromycin were generally one half those of roxithromycin, except for Corynebacterium sp. and Bacteroides fragilis against which the new macrolide was more active. On the other hand, roxithromycin exhibited a superior in vivo antibacterial activity in laboratory animals, being up to six times more potent than erythromycin in curing experimentally infected mice. Roxithromycin showed high blood levels and long half-lives of elimination in rodents after oral administration, and its bioavailability amounted to 72% in mice and 85% in rats, compared to less than 10% for erythromycin. Roxithromycin was widely distributed throughout the body with a high degree of penetration into all tissues, particularly in the lungs.

Supports and their use

Abstract: Novel supports useful in solid phase synthesis of oligonucleotides of the formula ##STR1## wherein ○P is a material selected from the group consisting of functionalized glass micropellets, silica functionalized by aminoalkyl trialkoxysilane capable of to obtain for ##STR2## Kieselguhr, polytetrafluoroethylene, cellulose and metallic oxides, m is an integer from 1 to 20, A is selected from the group consisting of alkyl of 1 to 20 carbon atoms, saturated cycloalkyl of 3 to 12 carbon atoms, phenyl and 5 to 6 member heterocycles, x and y are an integer from 0 to 20, x 1 is an integer from 1 to 20 and y 1 is an integer from 0 to 10, a process for the preparation of said supports, the use of said supports and intermediates.

Pharmacokinetics of ofloxacin and theophylline alone and in combination.

Abstract: The pharmacokinetic interactions of ofloxacin (2×200 mg) and theophylline (3×200 mg) were investigated in 12 healthy volunteers over a period of two weeks. In the first week, theophylline was given over five days to reach a steady state. In the second week, the combination of theophylline and ofloxacin was applied. Cmax, tmax, AUC0–8, the serum elimination constant and serum half-life of theophylline were not changed when theophylline was given alone or in combination with ofloxacin. The kinetic parameters of ofloxacin were in accordance with data from the literature.

Supports useful in solid phase synthesis of oligonucleotides

Abstract: Novel supports useful in solid phase synthesis of oligonucleotides of the formula ##STR1## wherein ○ is micro pellets of a material selected from the group consisting of glass, silica, Kieselguhr, polytetrafluoroethylene, cellulose and metallic oxides, m is an integer from 1 to 20, A is selected from the group consisting of alkylene of 1 to 20 carbon atoms, saturated cycloalkylene of 3 to 12 carbon atoms, phenyl and 5 to 6 member heterocycles, x is an integer from 0 to 20, x 1 is an integer from 0 to 10 and the amino group may be in the m-, p- or o-position, a process for the preparation of said supports, the use of said supports and intermediates.

Novel 10-substituted steroids

Abstract: A novel steroid of the formula ##STR1## wherein X is methylene and R is an optionally substituted carbocyclic aryl or heterocyclic aryl or optionally substituted vinyl or ethynyl or X is a simple bond or --S-- and R is optionally substituted carbocyclic aryl or heterocyclic aryl, R2 is methyl or ethyl, R3 is selected from the group consisting of optionally substituted alkyl of 1 to 8 carbon atoms and optionally substituted alkenyl and alkynyl of 2 to 8 carbon atoms, R4 is selected from the group consisting of hydrogen and acyl, ##STR2## is selected from the group consisting of ##STR3## R6 is selected from the group consisting of hydrogen and methyl, the wavy line indicates α or β- and the dotted line in 1(2) indicates the optional presence of a second carbon-carbon bond and novel process and intermediates therefore having anti-glucocorticoid activity.

Human B cell activation: selective sensitivity of the early stages to calcium channel-blocking drugs.

Abstract: The importance of Ca2+ in the early events of lymphocyte activation has been suggested by several studies. We examined the effect of calcium channel-blocking drugs (verapamil and nitrendipine) on the progression of human B cells through their activation cycle. Our results show that these drugs suppress the anti-mu-induced human B cell proliferation and interfere with the early events of the B cell activation in a dose-dependent fashion. This suppression correlates with a marked decrease in anti-mu-induced 45Ca2+ uptake. Calcium channel-blocking drugs inhibit the anti-mu-induced uridine incorporation and the appearance of the activation marker defined by the 4F2 monoclonal antibody. Calcium channel-blocking drugs also inhibit B cell proliferation induced by the costimulation with anti-mu antibody and B cell growth factor (BCGF). However, this inhibition takes place at the early (anti-mu-dependent) stage of B cell activation: the BCGF-dependent proliferation of in vitro anti-mu-activated B cells is only marginally inhibited. Finally the proliferation of Epstein-Barr virus-infected B cell lines is resistant to the effect of calcium channel-blocking drugs.

4H-triazolo [4,3-a][1,4] benzodiazepines, process for their preparation, their use as medicaments and compositions containing them

Abstract: 1. Claims for the contracting States CH, DE, GB, IT, LI, NL The compounds of formula (I) : see diagramm : EP0227539,P11,F1 in which R1 and R2 represent a hydrogen atom or an alkyl radical containing from 1 to 5 carbon atoms, R3 , R4 , R5 , R6 , identical or different, in any position on the benzene nuclei, represent a hydrogen atom, a hydroxyl radical, an alkyl radical containing from 1 to 4 carbon atoms, an Oalk1 radical, alk1 representing an alkyl radical containing from 1 to 4 carbon atoms, an NH2 , NHalk2 radical, alk2 representing an alkyl radical containing from 1 to 4 carbon atoms, an see diagramm : EP0227539,P11,F2 radical, alk3 and alk'3 , identical or different representing an alkyl radical containing from 1 to 4 carbon atoms, a halogen atom, a CF3 or an NO2 radical, on the condition that R5 and R6 does not represent at the same time a hydrogen atom, in all the racemic or optically active forms, as well as their addition salts with acids. 1. Claims for the contracting State ES Preparation process for compounds of formula (I) : see diagramm : EP0227539,P12,F2 in which R1 and R2 represent a hydrogen atom or an alkyl radical containing from 1 to 5 carbon atoms, R3 , R4 , R5 , R6 , identical or different, in any position on the benzene nuclei, represent a hydrogen atom, a hydroxyl radical, an alkyl radical containing from 1 to 4 carbon atoms, an Oalk1 radical, alk1 representing an alkyl radical containing from 1 to 4 carbon atoms, an NH2 , NHalk2 radical, alk2 representing an alkyl radical containing from 1 to 4 carbon atoms, see diagramm : EP0227539,P12,F3 radical, alk3 and alk'3 , identical or different, representing an alkyl radical containing from 1 to 4 carbon atoms, a halogen atom, a CF3 radical or an NO2 radical, on the condition that R5 and R6 do not represent at the same time a hydrogen atom, in all racemic or optically active forms, as well as their addition salts with acids, characterised in that a compound of formula II : see diagramm : EP0227539,P13,F1 in which R1 , R2 , R3 and R4 have the previous meanings, in the racemic or optically active form, is subjected to the action of a compound of formula (III) : see diagramm : EP0227539,P13,F2 in which R5 and R6 have the previous meanings, so as to obtain a compound of formula (I) in the racemic or optically active form, which is converted, if desired, into salts by the action of an acid.

Steroids substituted in position 10, their preparation and intermediates obtained in their preparation, their use as medicaments and pharmaceutical compositions containing them

Abstract: L'invention concerne les produits The invention relates to products ou X est -CH 2 - et R est un aryie eventuellement substitue, ou vinyle ou ethynyie eventuellement substitue ; where X is -CH 2 - and R is an optionally substituted aryie, or vinyl or ethynyl optionally substituted; ou X est un soufre ou une liaison et R est un aryle eventuellement substitue ; or X is a sulfur or a bond and R is an optionally substituted aryl; R 2 est methyle ou ethyle ; R 2 is methyl or ethyl; R 3 est alkyle, alkenyle ou alkynyle (1-8c) eventuellement substitue ; R 3 is alkyl, alkenyl or alkynyl (1-8C), optionally substituted; R 4 est H ou acyle ; R 4 is H or acyl; . . le trait pointlle indique la presence eventuelle d'une liaison ; the pointlle line indicates the optional presence of a bond; leur procede et des intermediaires de preparation, leur application comme medicaments et les compositions les renfermant. their process and intermediates for preparation, their use as medicaments and compositions containing them. Les produits (I) possedent une remarquable activite anti-glucocorticoide et, pour certains, glucocorticoide. The products (I) have a remarkable anti-glucocorticoid activity and, for some, glucocorticoid.

Early events in human B cell activation: metabolic pathways vary according to the first signal used.

Abstract: The effects of the calcium channel blocking drug Verapamil and of palmitoyl-carnitine (PTC), an inhibitor of protein-kinase C activity, on human B cell activation were measured. Both Verapamil and PTC inhibited the B cell proliferation induced by costimulation with anti-mu antibody and with 3 different growth factors: interleukin 2, 20-kDa B cell growth factor and 50-kDa B cell growth factor. Both uridine and thymidine incorporation induced by costimulation with ionomycin and phorbol 12-myristate 13-acetate (PMA) were inhibited by Verapamil and PTC. In contrast, B cell proliferation was resistant to Verapamil (while being still inhibited by PTC) in two situations: when B cells were costimulated with PMA and growth factors and when B cells previously activated in vitro (by anti-mu antibody or PMA) were stimulated with growth factors. These results confirm that the late stage (G1----S transition) of B cell activation is independent of Ca2+ entry. More importantly, they show that the initial events induced by anti-mu antibody and by PMA are based on different biochemical pathways: PMA would act on a subpopulation of B cells which has already received an early signal of activation in vivo. This emphasizes the functional and biochemical heterogeneity of the G0 stage among circulating B cells.

Different human B cell subsets respond to interleukin 2 and to a high molecular weight B cell growth factor (BCGF).

Abstract: After activation by anti-mu antibody human B cells acquire the ability to proliferate in the presence of recombinant interleukin 2 (IL 2), a 20-kDa mol. mass B cell growth factor (BCGF) and a high mol. mass BCGF (50-kDa BCGF). An anti-IL 2 receptor (IL 2R) monoclonal antibody inhibits the IL 2-dependent proliferation without affecting that induced by BCGF. B cells expressing the IL 2R after anti-mu antibody activation (IL 2R+ cells) were separated from those not expressing IL 2R (IL 2R- cells). IL 2 stimulated the proliferation of only IL 2R+ cells whereas the 20-kDa BCGF acted on both IL 2R+ and IL 2R- cells. Importantly, the 50-kDa BCGF supported the proliferation of IL 2R- cells whereas it was inactive on IL 2R+ cells. Thus, the B cell subset responding to the 50-kDa BCGF after anti-mu antibody activation is distinct from that responding to IL 2.

Triglycerides, process for therapeutical applications and compositions containing them

Abstract: The present invention concerns new triglycerides of Formula I: ##STR1## wherein R represents an acyl fragment of a polyunsaturated fatty acid containing 18 to 22 carbon atoms, the acyl fragment being capable of being oxidized, however, R cannot represent the acyl fragment of eicosatetrayn-5, 8, 11, 14-oic acid, and wherein n represents an integer varying from 2 to 16; a process for their preparation, their dietetic and therapeutic applications and compositions containing them.

Oxidized triglycerides having therapeutic utility

Abstract: The present invention concerns new triglycerides of Formula I: ##STR1## wherein R represents an acyl fragment of a polyunsaturated fatty acid containing 18 to 22 carbon atoms, the acyl fragment being capable of being oxidized, however, R cannot represent the acyl fragment of eicosatetrayn-5, 8, 11, 14-oic acid, and wherein n represents an integer varying from 2 to 16; a process for their preparation, their dietetic and therapeutic applications and compositions containing them.

Diffusion von Ofloxacin in menschliches Lungengewebe

Abstract: 17 Patienten, die wegen Lungenerkrankungen operiert werden musten, erhielten Ofloxacin. Die Applikation wurde 48 Stunden vor der Operation mit zweimal taglich 200 mg Ofloxacin begonnen; eine Stunde vor der Operation wurden nochmals 200 mg Ofloxacin verabreicht. Wahrend der Operation wurden gleichzeitig Blut- und Gewebeproben von gesunder und pathologisch veranderter Lunge entnommen. Die Ofloxacinspiegel wurden mittels HPLC bestimmt. Die Quotienten der Gewebe/Plasma-Konzentrationen betrugen im Mittel 3,5±0,4 bei gesundem Gewebe und 3,9±0,4 bei krankem Gewebe. Aus diesen Werten ist abzuleiten, das Ofloxacin in gesundes wie in atelektatisches Lungenparenchym gut penetriert.