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J Roux

Publications and source records attributed to J Roux.

At least 55 records · Page 3Linked to original sources
PubMed1995

Pharmacokinetics study of 14C-moxisylyte after percutaneous application to hairless rat.

The percutaneous pharmacokinetic parameters of 14C-thymoxamine (4-(2-dimethylaminoethoxy)-5-isopropyl-2-methyl phenyl acetate, moxisylyte, Carlytène) were studied on female hairless rats. Animals received 30.3 mg/kg of thymoxamine-base (CAS 54-32-0) percutaneously (dorsal skin). The decrease of the radiolabelled compound on the skin surface (drug penetration) and the appearance of the total radioactivity in plasma (drug absorption) were measured. The time-course study of the total radioactivity measured on the skin surface indicates a biphasic profile with a rapid decrease during the first h (t1/2 from 0 to 4 h = 1.4 h) and then a less rapid one (t1/2 after 4 h approximately 29 h). Plasma data demonstrated that 14C-thymoxamine was rapidly and almost entirely absorbed (91%) after percutaneous application. The values of absorption parameters suggest that thymoxamine is a compound with a high absorption process using this route of administration. The t(max) value was about 2 h and the half-life of absorption was 0.70 h. Compared to the apparent half-life of elimination observed after oral or i.v. administration (t1/2 = 9 h),the elimination phase of thymoxamine was relatively rapid after percutaneous administration (t1/2 = 15 h). The penetration /absorption phenomenon of thymoxamine base mainly located in the horny layer could explain the higher value of the half-life of elimination observed after percutaneous administration.

Administration, Cutaneous↗
PubMed1994

Participation of Ets transcription factors in the glucocorticoid response of the rat tyrosine aminotransferase gene.

We have previously shown that two remote glucocorticoid-responsive units (GRUs) of the rat tyrosine aminotransferase (TAT) gene contain multiple binding sites for several transcription factor families, including the glucocorticoid receptor (GR). We report here the identification of two novel binding sites for members of the Ets family of transcription factors in one of these GRUs. One of these binding sites overlaps the major GR-binding site (GRBS), whereas the other is located in its vicinity. Inactivation of the latter binding site leads to a twofold reduction of the glucocorticoid response, whereas inactivation of the site overlapping the GRBS has no detectable effect. In vivo footprinting analysis reveals that the active site is occupied in a glucocorticoid-independent manner, in a TAT-expressing cell line, even though it is located at a position where there is a glucocorticoid-dependent alteration of the nucleosomal structure. This same site is not occupied in a cell line that does not express TAT but expresses Ets-related DNA-binding activities, suggesting the existence of an inhibitory effect of chromatin structure at a hierarchical level above the nucleosome. The inactive Ets-binding site that overlaps the GRBS is not occupied even in TAT-expressing cells. However, this same overlapping site can confer Ets-dependent stimulation of both basal and glucocorticoid-induced levels when it is isolated from the GRU and duplicated. Ets-1 expression in COS cells mimics the activity of the Ets-related activities present in hepatoma cells. These Ets-binding sites could participate in the integration of the glucocorticoid response of the TAT gene with signal transduction pathways triggered by other nonsteroidal extracellular stimuli.

Animals↗
PubMed1994

Comparison of thymoxamine permeation between hairless rat and horse penile mucous membrane using an in vitro diffusion model.

Moxisylyte (or thymoxamine) administered intracavernously is known to improve erection in organically impotent patients. Prior to drug administration by percutaneous route, we have to define its in vitro permeation parameters after application of thymoxamine on both rat skin and horse penile mucous membrane. 24 h after drug application, the percentages of thymoxamine which diffused through the penile mucous and the rat skin were 88 and 75%, respectively. Thymoxamine flux varied according to the biological membrane tested. With regard to the penile mucous membrane, a maximal flux (1,774 nmol.h-1.cm-2) was observed 2.5 h after drug application, whereas for the rat skin a maximal flux (657 nmol.h-1.cm-2) was noted at 3.5 h. Thymoxamine flux decreased rapidly in the penile mucous membrane. This decrease was slower when thymoxamine penetrated the rat skin; the difference could be due to a different morphology of the tested biological membranes. In contrast to the rat skin, the external keratinized layer was absent in the penile mucous membrane. In conclusion, the ability of thymoxamine to penetrate easily and rapidly the biological membrane, and particularly the penile mucous membrane, suggests that thymoxamine could reach the pharmacological target represented by the corpus cavernosum of the penis.

Animals↗
PubMed1994

[Fatal ichthyosarcotoxism after eating shark meat. Implications of two new marine toxins].

A fish poisoning involving 188 hospitalizations occurred in November 1993, in Manakara, a middle-sized town on the south-east coast of Madagascar, following the ingestion of shark. A single shark was involved in this poisoning and was identified as Carcharinus leucas. There was no unusual characteristic of this shark or its meat. The attack rate was about 100%. First clinical signs appeared within five to ten hours after ingestion. The patients presented neurological symptoms almost exclusively, the most prominent being a constant, severe ataxia. Gastrointestinal troubles, like diarrhoea and vomiting were rare. The overall case-fatality ratio was close to 30% among the 200 poisoned inhabitants. Search for similar poisoning previously reported in this area was negative, and fishermen in Manakara usually eat that kind of shark without mistrust. Bacteriological and chemical origins were eliminated. Two liposoluble toxins were isolated from the shark liver and tentatively named carchatoxin-A and -B respectively. They were distinct from ciguatoxin in chromatographic properties.

Adult↗
PubMed1994

[Clinical immunology of hepato-splenic bilharziasis].

Field studies on immunity in human schistosomiasis gave evidence for a slow development with age of an acquired resistance to reinfection. Recent results support the idea of a progressive build-up of high levels of protective IgE, and probably IgA, overcoming the initial influence of blocking Ig G4 antibodies. Chemotherapy does not apparently modify the susceptibility to infection. A. Capron's candidate vaccine is now ready for human trials, and represents a promising tool in controlling schistosomiasis morbidity while diminishing the parasite transmission efficiency.

Adolescent↗
PubMed1994

[History of a hepatic lesion: Schistosoma mansoni bilharziasis].

Schistosomiasis mansoni is a widespread tropical disease affecting about 200 million people in the world (data from the World Health Organization). The adult worms, settled in the mesenteric venous plexus, can survive in the host during 5 to 20 years. They evade the immune response and are not, by themselves, the main cause of the pathological events. Most eggs are swept into the portal circulation and trapped in different systemic organs, including the liver. The continuous egg deposition results in a T cell-mediated granulomatous response that is responsible for the disease syndrome (chronic hepatitis associated with a dense fibrosis and a concurrent portal hypertension). Current immunological and molecular concepts on the modulation of the granuloma, and the associated fibrosis, lead to a better understanding of the pathogenesis of human schistosomiasis. Chemotherapy with praziquantel is presently the main approach of morbidity control, before using in conjunction a human vaccine still in development.

Granuloma↗
PubMed1994

[Why compare hepatosplenic bilharziasis in six African countries with the help of ultrasonography? Presentation of a WHO project including Madagascar].

During a morbidity survey in two endemic foci of hepatosplenic schistosomiasis in the malagasy Hauts Plateaux (Tetikanana, 80 km East of Ambositra and Lohanosy, in the vicinity of Antananarivo), the objectives of a comparative pathology WHO project are presented. The survey in Madagascar was concurrently organized by the Ministry of Health (Bilharziasis central laboratory, DLMT), the Parasitology Unit of the local Pasteur Institute and the Medical Parasitology Institute of Bonn University, in Germany. This was the fourth part of this investigation of the morbidity variation due to Schistosoma mansoni infection in six african countries, a project sponsored by the WHO within its TDR programme. This comparison was based on the standardized description of morbidity as visualized by echography, following the "Cairo-1990" and the "Hannover-Managil-1989" classifications, and on coprology. One of the main objectives of this study was to demonstrate a morbidity variation at the scale of the African region (due to different S. mansoni strains or to a variable genetic background within the studied human populations), while participating to an international standardization effort for field echography. The project was conducted since July 1991 by a constant medical staff from Bonn and Hannover german universities. Eight foci in four african countries (Senegal, Mali, Uganda and Madagascar) are still analyzed and we are presenting here the first results. The data of an independent ultrasonographic investigation, organized by the Blair Institute and the Danish Bilharziasis Laboratory in Zimbabwe, was kindly proposed for this comparison. This project will end with the study of two supplementary foci in Tanzania and Burundi.

Africa↗
PubMed1994

[Schistosomiasis mansoni infection in a hyperendemic region of midwestern Madagascar: epidemiology, morbidity and secondary effects of praziquantel treatment].

The examination of 544 inhabitants (93.2% of the whole population) of a village in the middle west of Madagascar, where Schistosoma mansoni is hyperendemic and where no previous antischistosomal treatment had been delivered at a community level, showed a prevalence rate of 61.8%. The highest prevalences and the most intense infections were observed in the 10-24 age group. The egg count decreases dramatically from the age of 25. A highly significant relationship was found between recent histories of bloody diarrhoea and S. mansoni eggs excretion. Clinical examination showed a high frequency of splenomegalies (62.2% > or = stade 2 Hackett), with two modes: one in the 10-14 age group and the other in the 35-39 age group. The respective liability of S. mansoni and malaria remain to be clarified. Side effects after treatment of the entire population with praziquantel were observed in 27.2% of treated individuals. Side effects occurred mainly in infected people. A highly significant relationship was found between intensity of infection and frequency of these side effects which are essentially mild and disappear in the 24 hours.

Adolescent↗
PubMed1994

[Evolution of Schistosoma mansoni bilharziasis in Ampefy (Lake Itasy) from 1986 to 1993].

In 1976, 1983, 1986 to 1989 and 1993, the population of Ampefy, on the shores of lake Itasy, was invited to participate in an active detection programme of Schistosoma mansoni infection. An increase in the global prevalence was observed from 1976 (17.0%) to 1983 (40.0%). This prevalence level was then stabilized during the four years annual selective treatment (1986 to 1989) and the mean intensity of infection for positive patients fell from 393 eggs/g to 271 eggs/g and the proportion of severe infections, with a high risk of developing "hepatosplenic disease", fell from 8% to 4.2%. Selective treatment was interrupted from 1989 to 1993, during which time the global prevalence rose to 70.6% and mean intensity of infection to 594 eggs/g, with 22% of those examined classified as severely infested. This local control programme, associating active detection with annual treatment, seems effective in stabilizing prevalence and intensity of infection in spite of a regular arrival of infested, and never treated, immigrants. However, its impact throughout time is limited.

Adolescent↗
PubMed1994

[Dengue 1 epidemic in the Grand Comoro Island (Federal Islamic Republic of the Comores). March-May 1993].

An epidemic of dengue fever occurred in Grande Comore island from March to May 1993. Dengue 1 virus has been isolated. The epidemic did not affect the other islands of the archipelago. No compound clinical picture, in particular hemorrhagic, was reported. A random sampling survey conducted towards the end of April showed that 26% of the population aged 5 years old or more had IgM dengue antibodies. The epidemic concerned essentially individuals under 45 years of age. The number of inhabitants of Grande Comore affected by the outbreak can be estimated between 56,000 and 75,000. The results of the sero-epidemiological survey allowed to find the serological scar of two previous epidemics of dengue: the first one around 1948, which may correspond with dengue 1, the other one in 1984, probably with dengue 2.

Adolescent↗
PubMed1993

Demographic reductions and genetic bottlenecks in humans: minisatellite allele distributions in Oceania.

Polynesians have lower heterozygosities at minisatellite VNTR (Variable Number of Tandem Repeat) loci than have Melanesians; this has been taken as evidence of population-size bottlenecks during the colonisation of Polynesia. We have analysed the allelic distribution of several minisatellite loci in the population of Rapa, a Polynesian island that is known to have undergone a demographic reduction of approximately 95% since first contact with European explores 200 years ago, leaving a surviving population of 120. We found that the minisatellite diversity of this population does not differ significantly from that of other Polynesian populations, and appears consistent with the neutral expectation of diversity assuming the infinite alleles model. This suggests that the demographic crisis that Rapa underwent did not perturb the allele distribution to the extent that the tests used here could detect. Thus we cannot say that a demographic change of this magnitude constitutes a genetic bottleneck detectable at these loci. The reduced diversity seen in Polynesia must therefore be explained either by more severe bottlenecks as might be expected during colonisation, or else by other causes.

Alleles↗
PubMed1993

MK-801 and enantiomers: potential antidepressants or false positives in classical screening models?

In the present experiments, the noncompetitive NMDA antagonist 5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclo-hepten-5,10-imine (MK-801) and its (+) and (-) enantiomers were tested in classical screening models used to detect potential antidepressants. The drug and its enantiomers were active in the tail suspension test (TST). The racemate was also active in the forced swimming test (FST). The effects in these tests occurred, however, at doses with marked stimulant activity. Further investigations (reserpine, apomorphine, and yohimbine tests) could not confirm the suspected antidepressant activity. Other NMDA antagonists--2-amino-7-phosphonoheptanoic acid (AP7), kynurenic acid, and 1-glutamic acid diethylester (GDEE)--showed no activity in the TST. These findings throw doubt concerning the potential antidepressant activity of MK-801 and other NMDA antagonists.

Animals↗
PubMed1993

Parasite virulence factors during falciparum malaria: rosetting, cytoadherence, and modulation of cytoadherence by cytokines.

To determine virulence factors of isolates of Plasmodium falciparum and the potential role of cytokines in cerebral malaria, 46 Malagasy patients presenting with cerebral (n = 10), severe (n = 10), and uncomplicated (n = 26) malaria were enrolled in a study. The capacity of 21 of 46 P. falciparum isolates to form rosettes in vitro and to adhere to human umbilical vein endothelial cells (HUVECs) that express intercellular adhesion molecule-1 receptors and to C32 amelanotic melanoma cells that express mainly CD36 receptors was investigated together with the effects of tumor necrosis factor alpha (TNF-alpha), granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-6 alone and in two-by-two combinations on the cytoadherence of infected erythrocytes to HUVECs. Plasma levels of these cytokines were also measured in the patients at admission. The percentage of rosette formation was higher for the isolates from patients with cerebral (n = 6; 19.5%) and severe (n = 6; 30.5%) malaria than for those from patients with uncomplicated malaria (n = 9; 5%) (P < 0.002). The cytoadherence properties of the isolates did not differ among the three groups whatever the target cell used, but adherence to melanoma cells was systematically higher than that to HUVECs. Adhesion to HUVECs was increased more after TNF-alpha stimulation than after GM-CSF, IL-3, or IL-6 stimulation (P < 0.01). Only the combination of TNF-alpha and IL-3 enhanced cytoadherence more than TNF-alpha used alone (P < 0.02). No difference in the modulation of cytoadherence by cytokines was found in relation to the severity of the disease. TNF-alpha and IL-6 levels in peripheral blood were higher in the patients with cerebral and severe malaria than in the patients with uncomplicated malaria (P < 0.005). Most of the patients' sera contained little or no IL-3 or GM-CSF. Our results challenge the role of intercellular adhesion molecule-1 as the principal receptor mediating the cytoadherence of P. falciparum-infected erythrocytes and contrast with data obtained in the murine model.

Adolescent↗
PubMed1993

[Epidemiological malaria surveillance in 3 villages of the Madagascar highlands].

Results of the epidemiological surveillance of falciparum malaria carried out since 1987 in three villages of the malagasy Highlands are reported. They clearly show the unsteady endemo-epidemic characteristic of the disease with highly variable transmission levels according to foci. At Manarintsoa, a south-western village 20km away from the Capital, the disease has now fully disappeared after the ravage of 1986. But it might reappear with new imported cases and by lack of antivectorial measures. Although Anopheles arabiensis had been rare and its aggressivity rate weak (0.91-2 infecting bites per year per man), surveillance is indispensable for the future. An Ankazobe and Mahavelona, two north-western localities respectively 100km and 65km away from Antananarivo, malaria is endemic with periodic outbreaks during rainy season. At Ankazobe, Anopheles funestus is the main vector maintaining endemic in this area while the role of Anopheles gambiae l.s. is only secondary. At Mahavelona, because of the weak presence of vectors, the treatment protocol by Quinimax has been applied in order to study transmission. This study obviously shows that contrary to set ideas in the Highlands, backward transmission is possible up to the first months of the austral winter (June-July). In these two last villages, adults have acquired some premunition.

Adolescent↗
PubMed1993

[Situation of endemic rabies in Madagascar].

The course of endemic rabies in Madagascar between 1982 and 1991 is related. Rabies has been raging over the whole island and dog is essentially affected, constituting the single vector of human rabies cases. The authors recall the main measures of struggle against rabies.

Adolescent↗