Showing papers by "Roussel Uclaf published in 1987"

Enzymatic protection against peroxidative damage in isolated brain capillaries.

Abstract: The content of polyunsaturated fatty acids, the activities of superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase, and catalase, and the concentration of reduced glutathione were measured in cerebral microvessels isolated from rat brain. Polyunsaturated fatty acids, mainly arachidonic, linoleic, and docosahexaenoic acids, accounted for 32% of total fatty acids in cerebral microvessels. Whereas total SOD activity in the microvessels was slightly lower than that found in cerebrum and cerebellum, glutathione peroxidase and glutathione reductase activities were twice as high and catalase activity was four times higher. Glutathione peroxidase in microvessels is active on both hydrogen peroxide and cumen hydroperoxide, and it is strongly inhibited by mercaptosuccinate. After several hours of preparation, the concentration of reduced glutathione in isolated microvessels was 0.7 mumol/mg of protein, which corresponds to a concentration of approximately 3.5 mM. Our results indicate that the blood-brain barrier contains large amounts of peroxide-detoxifying enzymes, which may act, in vivo, to protect its highly polyunsaturated membranes against oxidative alterations.

Regional distribution of high-affinity γ-[3H]hydroxybutyrate binding sites as determined by quantitative autoradiography

Abstract: The distribution of high-affinity binding sites for gamma-[3H]hydroxybutyrate in coronal sections of rat brain was studied by quantitative autoradiographic techniques. Binding sites for this naturally occurring substance, which may possibly have a neurotransmitter role, are concentrated in some restricted areas of the brain, particularly in the limbic system. The hippocampus (especially field CA1 of Ammon's horn, at 292 fmol/mg of tissue), septum (72 fmol/mg of tissue), and cortex (frontal, 113 fmol/mg of tissue; parietal, 103 fmol/mg of tissue; cingulate, 114 fmol/mg of tissue; and entorhinal, 134 fmol/mg of tissue) show pronounced labeling with gamma-[3H]hydroxybutyrate. Binding is much lower in caudatus-putamen (50 fmol/mg of tissue), thalamus, and hypothalamus. Caudal parts of the brain (cerebellum, pons, and medulla) are practically devoid of binding sites. These results strongly support a functional role of endogenous gamma-hydroxybutyrate in particularly restricted areas of the rat brain.

A study of the interaction of roxithromycin with theophylline and carbarmazepine

Abstract: There have been reports of an interaction when theophylline and macrolides are given together, and also when carbamazepine is given with macrolides. We compared the kinetics of theophylline and carbamazepine, given alone and then in combination with roxithromycin. Roxithromycin had little effect on the pharmacokinetics of theophylline and none on carbamazepine, and roxithromycin can be given with either of the drugs without any need to alter the dose.

Diffusion of ofloxacin into human lung tissue.

Abstract: Ofloxacin 200mg twice daily was administered to 17 patients with pulmonary disorders, which necessitated surgery, during the preceding 48 hours and 200mg was administered 1 hour before the operation. During surgery, blood samples and specimens of healthy and diseased lung tissues were taken simultaneously. Ofloxacin levels were determined by HPLC. The mean values of the tissue concentration/plasma concentration ratio were 3.5 ± 0.4 for the healthy tissue and 3.9 ± 0.4 for the diseased tissue. These values reflected good penetration of ofloxacin into both healthy and atelectasic pulmonary parenchyma.

Effects of single oral doses of clobazam, diazepam and lorazepam on performance tasks and memory.

Abstract: The effects on memory and psychomotor performance and the subjective effects of three anxiolytic benzodiazepines (lorazepam 2 mg, diazepam 10 mg and clobazam 20 mg p.o.) have been evaluated in a double-blind, placebo-controlled, cross-over study in 10 healthy volunteers.

Steroids including a spiro ring in position 17, the process for their preparation and their use

Abstract: ##STR1## Products having the formula (I) wherein R1 is an aryl or aralkyl, R2 is a hydrocarbonated radical (1-18 carbon atoms), the dotted lines indicate an optional bond, the cycles A, B and C represent (II), (III), (IV), (V), (VI); R' and R" are H, alkyl (1-4 carbon atoms). Re is H, alkyl (1-6 carbon atoms), acyl, and their salts, their preparation, their application as medicaments, the pharmaceutical compositions containing them and intermediaries.

19-Nor or 19-nor D-homo steroids substituted at position 11 beta by a phenyl group substituted by an alkynyl group, process for their preparation, their use in medicaments and pharmaceutical compositions containing them

Abstract: 1. The products of formula I : see diagramm : EP0245170,P90,F1 in which R1 represents an alkynyl radical having from 2 to 8 carbon atoms optionally substituted by a radical selected from the radicals, hydroxyl, halogen, trialkylsilyl, alkoxy, alkylthio, dialkylamino and oxo, R2 represents an alkyl radical having from 1 to 3 carbon atoms, the rings _A and _B have one of the following structures ; a/. either _A and _B represent the group : see diagramm : EP0245170,P90,F2 in which R' and R" identical or different represent a hydrogen atom or an alkyl radical having from 1 to 4 carbon atoms ; b/. or _A and _B represent the group : see diagramm : EP0245170,P90,F3 in which Rx represents a hydrogen atom or an ORe group in which Re represents a hydrogen atom, an alkyl radical containing from 1 to 6 carbon atoms optionally substituted by a dialkylamino radical or an acetyl or propionyl radical ; c/. or _A and _B represent the group : see diagramm : EP0245170,P90,F4 d/. or _A and _B represent the group : see diagramm : EP0245170,P90,F5 e/. or _A and _B represent the group : see diagramm : EP0245170,P91,F1 in which R3 represents a hydrogen atom, an alkyl radical having from 1 to 8 carbon atoms or an aralkyl radical having from 7 to 15 carbon atoms ; - the group of formula : see diagramm : EP0245170,P91,F2 represents : a/. either : see diagramm : EP0245170,P91,F3 in which R3 and R4 , identical or different, represent either a hydrogen atom, a hydroxyl radical, an Oalk4 , or see diagramm : EP0245170,P91,F4 radical, alk4 and alk5 representing an alkyl radical having from 1 to 8 carbon atoms or a benzyl radical ; an alkyl, alkenyl or alkynyl radical having at the most 8 carbon atoms or a phenyl, benzyl or phenylethyl or pyridylethynyl, thienyl or furyl radical, each of these radicals being optionally substituted by one or more radicals selected from the group formed by the radicals hydroxy, alkoxy and alkylthio having from 1 to 4 carbon atoms, the halogen atoms and the dialkylamino radical, or R3 and R4 together form the following radicals : see diagramm : EP0245170,P91,F5 see diagramm : EP0245170,P91,F6 see diagramm : EP0245170,P91,F7 see diagramm : EP0245170,P91,F8 see diagramm : EP0245170,P91,F9 see diagramm : EP0245170,P91,F10 see diagramm : EP0245170,P91,F11 see diagramm : EP0245170,P91,F12 see diagramm : EP0245170,P91,F13 see diagramm : EP0245170,P91,F14 see diagramm : EP0245170,P91,F15 see diagramm : EP0245170,P91,F16 see diagramm : EP0245170,P91,F17 see diagramm : EP0245170,P91,F18 in which R5 and R6 together form a hydrogen atom or an alkyl radical having from 1 to 4 carbon atoms, M represents a hydrogen, sodium or potassium or lithium atom, R20 represents an alkyl radical optionally substituted by hydroxyl and R17 represents a hydrogen atom or an acetyl radical, Y and Z represent the following groups : see diagramm : EP0245170,P92,F1 see diagramm : EP0245170,P92,F2 see diagramm : EP0245170,P92,F3 see diagramm : EP0245170,P92,F4 see diagramm : EP0245170,P92,F5 in which R7 and R8 represent an alkyl radical having from 1 to 4 carbon atoms ; b/. or : see diagramm : EP0245170,P92,F6 in which R3 , R4 and Y-Z have the definitions previously indicated, the wavy lines meaning that the substituents R2 , R7 and R8 acan be found in one or other of the possible configurations, as well as the addition salts of the products of formula I with acids and bases.

Novel cosmetic compositions

Abstract: Novel cosmetic compositions for skin care and retarding of skin aging effects (e.g., by hydrating and moisturizing the skin) containing an amount of a mixture of oenethera oil and spleen tissue extract sufficient to retard skin aging effects (e.g., by hydrating and moisturizing the skin) and a method of treating skin.

An evaluation of tolerance of roxithromycin in adults

Abstract: This review deals with tolerance of a new macrolide, roxithromycin from data collected from a number of studies in adults. A total of 2917 adults, 2519 given roxithromycin 150 mg bid, were recruited into 17 multicentre comparative or non-comparative studies. Nine studies were double-blind, against doxycycline, erythromycin estolate (EES), lymecycline or cephradine. Overall the drug was well tolerated: side-effects possibly or probably related to roxithromycin were noted in only 4.1% (120/2917) of all patients, and in 3.1% (15/480) of elderly subjects. The gastrointestinal tolerance of roxithromycin was significantly better than that of doxycycline in four trials, and better than that of erythromycin ethylsuccinate in one study. The incidence of drug-related liver function test abnormalities following roxithromycin therapy was low and compared favourably with data published on erythromycin. Roxithromycin shows a satisfactory safety profile at the recommended daily dosage of 150 mg bid in adults.

Contragestion by antiprogestin RU 486: a review.

Abstract: The steroidal derivative RU 486 (17β-hydroxy-11β-(4-dimethyl-aminopheny 1)-17α-(prop-1-ynyl)-estra-4,9-dien-3-one) is the first potent antiprogestin in medical use. Acting reversibly at the molecular level of receptor binding, RU 486 blocks progesterone action and allows endocrine functions to return quickly to normal after its use. However, target cells dynamics that depend upon a continuity of progesterone action will be irreversibly disrupted. In normal women RU 486 acts during the luteal phase in the endometrium, provoking bleeding, and also decreases LH secretion which results in luteolysis. In pregnant women, if affects the decidual, increases myometrial contractility and ripening of the cervix, and ultimately leads to termination of pregnancy. Detachment of the trophoblast leads to a fall in chronic gonadotrophin. Clinical studies indicate that RU 486 can be a very efficient agent for the termination of early pregnancy, and as a postcoital menstrual regulator. The failures observed when RU 486 is given alone may be overcome by the additional use of oxytocics. A small amount of prostaglandin given at the end of RU 486 treatment gives satisfactory results at up to 8 weeks of amenorrhea. Treatment with RU 486 is short term, and apparently has no significant side-effects despite the compound's antiglucocorticosteroid activity.

9-alpha-hydroxy steroids, process for their preparation, process for the preparation of the corresponding 9(11)-dehydro derivatives and pharmaceutical preparations containing said steroids

Abstract: New 9-alphahydroxy steroids are prepared by the introduction of substituents on the D-ring of 9-alpha-hydroxy-androst-4-ene-3,17-dione. The resulting compounds are useful intermediates in the synthesis of corticosteroids.

Novel 11 β-alkynylphenyl-10-nor-steroids

Abstract: Novel 11β-alkynylphenyl-19-nor-steroids of the formula ##STR1## wherein R 1 is alkynyl of 2 to 8 carbon atoms optionally substituted with at least one member of the group consisting of --OH halogen, trialkylsilyl of 1 to 6 alkyl carbon atoms, alkoxy and alkylthio of 1 to 6 carbon atoms and dialkylamino of 1 to 6 alkyl carbon atoms having remarkably antiprogestomimetic and antiglucocorticoidal activity.

1,2,5,6-Tetrahydropyridine-3-carboxaldehyde oxime derivatives, process for their preparation, compositions containing them and their use as medicines

Abstract: L'invention a pour objet les composes de formule (I) : The invention relates to compounds of formula (I): dans laquelle R represente un atome d'hydrogene, un radical alcoyle lineaire, ramifie ou cyclique, sature ou insature, renfermant jusqu'a 8 atomes de carbone, eventuellement substitue par un radical carboxy libre ou esterifie ou R represente un radical aralcoyle renfermant jusqu'a 10 atomes de carbone et R′ represente un radical alcoyle, lineaire ou ramifie, sature ou insature, renfermant jusqu'a 8 atomes de carbone, un radical -COalc₁ ou un radical -(CH₂)₂N(alc₂)₂, alc₁ et alc₂ representant un radical alcoyle renfermant jusqu'a 8 atomes de carbone, ainsi que leurs sels d'addition avec les acides, leur preparation, leur application comme medicaments et les compositions les renfermant. wherein R represents a hydrogen atom, a linear alkyl, branched or cyclic, saturated or unsaturated, containing up to 8 carbon atoms, optionally substituted by a carboxy radical free or esterified or R represents an aralkyl radical containing up to 10 carbon atoms and R 'represents an alkyl radical, linear or branched, saturated or unsaturated, containing up to 8 carbon atoms, a radical -COalc₁ or a radical - (CH₂) ₂N (alk₂) ₂ radical, and alc₁ alc₂ representing an alkyl radical containing up to 8 carbon atoms, and their addition salts with acids, their preparation, their use as medicaments and compositions containing them.

9-alpha-hydroxysteroids, process for their preparation and process for the preparation of the corresponding 9(11)-dehydro-derivatives.

Abstract: New 9-alpha-hydroxy steroids are prepared by the introduction of substituents on the D-ring of 9-alpha-hydroxy-androst-4-­ene-3,17-dione. The resulting compounds are useful intermediates in the synthesis of corticosteroids.

The cytosolic free calcium in anti-μ-stimulated human B cells is derived partly from extracellular medium and partly from intracellular stores

Abstract: The inositol phospholipid metabolism and the increase in cytosolic free Ca2+ concentration ([Ca2+]i) into the cell are recognized as two important events in the anti-mu-induced B cell activation. The anti-mu stimulation caused the [3H]inositol incorporation and also a rapid increase in [Ca2+]i from 85 nM to 285 nM. This signal returned to baseline a few minutes after stimulation. By using the fluorescent indicator quin-2 we demonstrated that this [Ca2+]i uptake was derived part from extracellular medium and part from intracellular stores. Both EGTA (a calcium chelator) and TMB.8 (a drug which interferes with Ca2+ sequestration by smooth endoplasmic reticulum) partially suppressed the intracellular Ca2+ uptake and were fully inhibitory when added together. The role of Ca2+ from intracellular stores may also be evidenced in calcium-free experiments, or in permeabilized experiments using exogenous inositol 1,4,5-trisphosphate (IP3, the putative mobilizer of intracellular Ca2+). Preventing the increase in [Ca2+]i also prevents the apparition of early activation makers. These results are consistent with the hypothesis that the Ca2+ increase in B cells stimulated by anti-mu is caused by the generation of IP3 during the phosphatidyl-inositol metabolism and also by the entry of extracellular Ca2+ through the plasma membrane.

Fertility control with RU 486.

Abstract: RU 486 is a synthetic steroid possessing antiprogestin and antiglucocorticoid activities. This paper summarizes the main pharmacological properties of this molecule. It is now under the phase II-III c