In vivo antimalarial activities of mono- and bis quaternary ammonium salts interfering with Plasmodium phospholipid metabolism.

We previously showed that quaternary ammonium salts have potent antimalarial activities against the blood stage of drug-resistant Plasmodium falciparum. In the present study, 13 compounds of this series were comparatively assessed in murine in vivo malarial models. Mice infected with Plasmodium berghei were successfully treated with 11 quaternary ammonium salts in a 4-day suppressive test with a once-daily intraperitoneal administration.

Potent inhibitors of Plasmodium phospholipid metabolism with a broad spectrum of in vitro antimalarial activities.

We characterized the potent in vitro antimalarial activity and biologic assessment of 13 phospholipid polar head analogs on a comparative basis. There was a positive relationship between the abilities of the drugs to inhibit parasite growth in culture and their abilities to specifically inhibit phosphatidylcholine biosynthesis of Plasmodium falciparum-infected erythrocytes. Maximal activity of G25 was observed for the trophozoite stage of the 48-h erythrocytic cycle (50% inhibitory concentration, 0.

Persistence of tight junctions and changes in apical structures and protein expression in choroid plexus epithelium of rats after short-term head-down tilt.

Major alterations of choroidal cell polarity and protein expression were previously shown to be induced in rats by long-term adaptation to space flight (14 days aboard a space shuttle) or anti-orthostatic suspension (14 and 28 days) performed by tilting rats head-down (i.e. using a ground-based model known to simulate several effects of weightlessness).

Hindlimb-suspension and spaceflight both alter cGMP levels in rat choroid plexus.

Effects of actual and simulated weightlessness on choroidal guanylate cyclase activity were evaluated by assaying the production of cyclic guanosine monophosphate (cGMP), a second messenger involved in mechanisms regulating the secretion of cerebrospinal fluid (CSF) in choroid plexus. Cyclic cGMP was measured, using radio-immunoassay, in choroidal extracts of hindlimb-suspended rats (HLS rats), adapted to an anti-orthostatic restraint for 30 min., or for 3, 9 or 14 days and after a 17-day spaceflight (Life and Microgravity SpaceLab experiment; LMS).

Phenotype modulation in primary cultures of aortic smooth muscle cells from streptozotocin-diabetic rats.

Diabetes mellitus is a major risk factor for atherosclerosis. In atherosclerotic lesions, arterial smooth muscle cells (SMC) change from a contractile to a synthetic phenotype characterized by active proliferation. A similar phenotype modulation occurs in vitro when isolated arterial SMC are grown in culture and is characterized by both changes in cell morphology and a typical switch in actin isoform expression.

Ependymal and choroidal cells in culture: characterization and functional differentiation.

During the past 10 years, our teams developed long-term primary cultures of ependymal cells derived from ventricular walls of telencephalon and hypothalamus or choroidal cells (modified ependymal cells) derived from plexuses dissected out of fetal or newborn mouse or rat brains. Cultures were established in serum-supplemented or chemically defined media after seeding on serum-, fibronectin-, or collagen-laminin-coated plastic dishes or semipermeable inserts. To identify and characterize cell types growing in our cultures, we used morphological features provided by phase contrast, scanning, and transmission electron microscopy.

Choroidal readaptation to gravity in rats after spaceflight and head-down tilt.

To determine when choroidal structures were restored after readaptation to Earth gravity or orthostatic position, fine structure and protein distribution were studied in rat choroid plexus dissected either 6 h [Space Life Sciences-2 (SLS-2) experiments] or 2 days [National Institutes of Health-Rodent 1 (NIH-R1) experiments] after a spaceflight, or 6 h after head-down tilt (HDT) experiments. Apical alterations were noted in choroidal cells from SLS-2 and HDT animals, confirming that weightlessness impaired choroidal structures and functions. However, the presence of small apical microvilli and kinocilia and the absence of vesicle accumulations showed that the apical organization began to be restored rapidly after landing.

Effects of an 11-day spaceflight on the choroid plexus of developing rats.

Cellular distributions of ezrin, a cytoskeletal protein involved in apical cell differentiation in choroid plexus, and carbonic anhydrase II, which is partly involved in the cerebrospinal fluid production, were studied by immunocytochemistry, at the level of choroidal epithelial cells from the lateral, third and fourth ventricles in normal or experimental fetuses, in parallel with the ultrastructure of apical microvilli, observed by transmission electron microscopy. We compared choroid plexuses from developing normal rats (gestational day 15 to birth) with choroid plexuses from 20-day-old rat fetuses, developed for 11 days in space, aboard a space shuttle (NASA STS-66 mission, NIH-R1 experiments), from gestational day 9 to day 20. The main changes observed in fetuses developed in space were demonstrated by immunocytochemistry and concerned the distribution of ezrin and carbonic anhydrase II.

Changes in apical organization of choroidal cells in rats adapted to spaceflight or head-down tilt.

Structural changes observed in choroid plexuses from rats dissected aboard a space shuttle, on day 13 of an orbital flight (NASA STS-58 mission, SLS-2 Experiments) demonstrated that choroidal epithelial cells display a modified organization in a microgravitational environment. Results were compared with ultrastructural observations of choroid plexus from rats maintained under anti-orthostatic restraint (head-down tilt) for 14 days. In both experiment types, the main alterations observed by transmission electron microscopy, at the level of choroidal epithelial cells from the third and fourth ventricles, concerned the formation and the organization of apical microvilli, whereas pseudopod-like structures appeared.

Choroidal responses in microgravity. (SLS-1, SLS-2 and hindlimb-suspension experiments).

Fluid and electrolyte shifts occurring during human spaceflight have been reported and investigated at the level of blood, cardiovascular and renal responses. Very few data were available concerning the cerebral fluid and electrolyte adaptation to microgravity, even in animal models. It is the reason why we developed several studies focused on the effects of spaceflight (SLS-1 and SLS-2 programs, carried on NASA STS 40 and 56 missions, which were 9- and 14-day flights, respectively), on structural and functional features of choroid plexuses, organs which secrete 70-90% of cerebrospinal fluid (CSF) and which are involved in brain homeostasis.

ANP binding sites are increased in choroid plexus of SLS-1 rats after 9 days of spaceflight.

Specific alpha-rat 28-amino acid atrial natriuretic peptide [ANP(99-126)] (rANP) binding sites in choroid plexus and meningia of rats flown for 9 days on the mission STS-40 (SLS-1) carried on the space shuttle Columbia in June 1991 were analyzed after incubation of brain sections with 125I-rANP and autoradiography, using computer-assisted microdensitometric image analysis. The number of 125I-rANP binding sites (expressed by Bmax values) in the choroid plexus of lateral and third ventricles of these rats was significantly increased (x 1.5-2.

Heart and plasma atrial natriuretic peptide (ANP) in response to long-term endurance training in rats.

Long-term endurance training effects on heart and plasma ANP were investigated in male Wistar rats. Maximal O2 uptake (VO2max) was significantly higher in trained groups, when they are used as their own control. After 3, 4, and 5 weeks of endurance training, VO2max was respectively increased by 7.

Suprachiasmatic nucleus lesions abolish photoperiod-induced changes in the testis function and GnRH immunoreactivity in the mink, a short-day breeder.

Testicular activity (testis volume and plasma testosterone) and immunoreactive GnRH hypothalamic system were examined after suprachiasmatic nucleus (SCN) lesion in the mink, a short-day breeding mammal, whose sexual activity is inhibited by day lengths exceeding 10 h. In animals maintained under a natural photoperiod, SCN destruction performed during the period of maximum sexual activity (February) was shown to have no effect on onset of the testicular inactive period which begins at the end of winter and continues through spring. On the other hand, while gonadal activity began again at the end of autumn in intact animals, minks that had undergone SCN destruction remained sexually inactive until the end of the experiment period (February).

Distribution of arrestin-like protein and beta-subunit of GTP-binding proteins in quail choroid plexuses.

Monoclonal antibodies (Mabs) directed against retinal arrestin (S-antigen) were used to detect and characterize this protein in choroid plexus (CP) of quails maintained during eight days, either under long-day photoperiods or in constant darkness. Immunocytochemistry and Western blotting confirmed the presence and the distribution of an arrestin-like protein in quail CP. Arrestin-like immunoreactivities in CP were compared with those obtained with Mabs to beta 36-subunit of G proteins (G beta), alpha-subunit of transducin and rhodopsin.

[Monoclonal antibodies obtained against G-protein epitopes: comparison of immunoreactions seen in the brain, retina and striated muscular tissue].

Monoclonal antibodies have been obtained against a purified fraction of brain G proteins containing the Gi alpha, G0 alpha, G beta, and G gamma subunits. After characterization, two monoclonal antibodies have been used to detect the cellular distribution of the two epitopes in neural, retinal and muscular tissues: ELISA, cross-dot and Western blot demonstrated that F.IV.

[Identification of a protein related to the S-antigen in choroid plexus in quails].

Using monoclonal and polyclonal antibody immuno-fluorescence, various areas of the quail diencephalon were tested immunocytochemically for the presence of S-antigen, which is a regulatory protein of retinal photoreceptors. In adult quail and embryos (from day 13 until hatching), S-antigen immunoreactivity was demonstrated in the cytoplasm of epithelial cells in the choroid plexus of the third ventricle. Similar data have previously been obtained in quail retinal photoreceptors.

Effect of short exposure to cold on plasma thyroxine in Coturnix quail: role of the infundibular complex and its neural afferents.

Exposure of control quail to low ambient temperature (4 degrees) for a short duration (15 min) led to a rapid increase in plasma thyroxine (T4) levels. A peak appeared 40 min after the cold began and was followed by a progressive and slow decline. T4 levels were elevated in birds maintained for up to 3 hr at 4 degrees.

Comparison of plasma thyroxine levels following short exposure to cold and TRH administration in intact and pituitary autografted quail (Coturnix coturnix japonica).

The thyrotropic functional abilities of ectopically transplanted anterior pituitaries were tested by subjecting quail bearing their adenohypophysis in juxtarenal position either to a short cold exposure or to an intravenous injection of TRH. Thyroxine was determined in plasma samples collected from 20 to 120 min after treatment. Intact birds exhibited increasing T4 levels up to a peak at 40 min, then decreasing slowly within 2 hr after either cold or TRH stimulation.

[Repercussions of anterior hypothalamic lesions on nycthemeral variations of plasma thyroxine and corticosterone in the pigeon].

Plasma thyroxine and corticosterone levels were determined by competitive protein binding assay, at 3 hr intervals, throughout the photoperiod. Pigeons were kept in controlled environment (21 +/- 1 degree C; 14L6-20: 10D). Intact controls exhibited low thyroxine (T4) and corticosterone (B) levels for the light phase of the photoperiod.

[Nycthemeral variations of thyroxine levels in the quail: effect of ambient temperature].

Plasma T4 levels were determined at 2 hr intervals in male quail reared under 18 L6-24 : 6D and 26 +/- 1 degrees C. Low thyroxinemia (4.7 -5.

[Role of the infundibular complex and its neural afferents in the photosexual reflex in the quail].

The photosexual reflex was suppressed in quail after bilateral preoptic lesions. However an anterior-lateral de-afferentation of the hypothalamus of previously preoptic-lesioned quail resulted in partial photo-induced testis growth. As a working hypothesis, it is suggested that the preoptic area may control some unknown extrahypothalamic influences in order to modulate the gonadotropin controlling function of the infundibular area.

Retrograde transport of horseradish peroxidase from the preoptic-anterior hypothalamic region to retinal ganglion cells in quail.

Horseradish peroxidase was injected in the preoptic-anterior hypothalamic area of intact male quail and reacted with 3,3'-diaminobenzidine and hydrogen peroxide in eye sections. Cells labelled with peroxidase reaction product were found in the ganglion layer of the retina. One possible function of such retinal-hypothalamic connections might be to participate in the photosexual reflex.

The effect of lesions of the epithalamus on plasma aldosterone and corticosterone levels in Japanese quail.

The peripheral plasma aldosterone and corticosterone concentrations were measured by CPBA and RIA method in Japanese quails in which the subcommissural organ (SCO) or the habenula had been destroyed. Lesion of the SCO reduced the plasma aldosterone level by 50%. The lesion of n.

Suppression of pineal multiunit response to flash after habenular lesion in quail.

Habenular nuclei were completely destroyed in male photostimulated and nonphotostimulated quail (Coturnix coturnix japonica). Lesion of the nuclei habenulae led to a markedly increased pineal multiunit activity (MUA) pattern in both long and short daily photoperiods compared to control values. Intact, as well as habenular lesioned birds, showed a lower level of pineal MUA under long-day rearing than under short-day rearing.