Biomedical subjects

J M Robert

Publications and source records attributed to J M Robert.

At least 19 recordsLinked to original sources

PubMed2002

In vitro and in vivo antileishmanial activity of 2-amino-4,6-dimethylpyridine derivatives against Leishmania mexicana.

Leishmania mexicana promastigote and intracellular amastigote growths were inhibited by the water-soluble furan-2-carboxamide issued from the pharmacophore 2-amino-4,6-dimethylpyridine with IC50 values of 69 +/- 2 and 89 +/- 9 microM, respectively. This compound was also tested against established L. mexicana infection in susceptible BALB/c mice; an intraperitoneal administration of 10 mg/Kg/day during five consecutive days induced a high reduction in the amastigote burden of the poplitea lymph node (81 +/- 6.4%), the spleen (80 +/- 1.6%) and the liver (73 +/- 9%). Approach of the mechanism of antileishmanial activity of this compound, assessed by the flow cytometry, showed a reduction in the protein and DNA synthesis. Finally, an actual increase of the in vitro antileishmanial activity was obtained by replacement of the amidic function by an imidazolidin-2-one moiety. In this new series, two of the N-substituted derivatives showed IC50 values of 13 +/- 0.5 and 7 +/- 3 microM in intracellular amastigotes constituting new promising compounds for further studies.

Animals↗

PubMed2001

Effects of tumour necrosis factor-alpha synthesis inhibitors on rat trinitrobenzene sulphonic acid-induced chronic colitis.

The fact that tumour necrosis factor-alpha (TNF-alpha) is clearly involved in the pathogenesis of intestinal bowel disease, especially Crohn's disease, suggests that TNF-alpha synthesis inhibitors could be beneficial for treatment. The present study assessed the effect of chronic oral gavage of two in vitro TNF-alpha synthesis inhibitors, JM 34 maleate or [N-(4,6-dimethylpyridin-2-yl)-furane-2-carboxamide)] maleate and XC 21 or (N-betapicolyl-tetrafluorophtalimide), on colonic inflammation in trinitrobenzene sulphonic acid-induced colitis in rats. Rats received JM 34 maleate (100 mg/kg) and XC 21 (50 mg/kg) 1 h before colitis induction and then daily for 8 days by oral gavage. The colon was removed on day 8 and processed for clinical score, myeloperoxidase activity, and soluble TNF-alpha release. Treatment with XC 21, as well as dexamethasone and sulphasalazine, reduced colonic damage and decreased (except with dexamethasone) the incidence of diarrhoea. JM 34 maleate failed to improve the clinical signs of chronic colitis. After trinitrobenzene sulphonic acid-induced colitis, myeloperoxidase activity and TNF-alpha colonic mucosal production were substantially increased compared to the control (saline instillation). Both of these inflammatory indicators were then significantly decreased (P< or =0.05) after the four chronic treatments (JM 34 maleate, XC 21, sulphasalazine, and dexamethasone). XC 21 appeared to be as efficient as sulphasalazine in improving colonic inflammation.

Animals↗

PubMed2001

Variable stereochemistry in highly branched isoprenoids from diatoms.

C(25) highly branched isoprenoid (HBI) alkenes are ubiquitous lipids found in geochemical samples around the globe. The origins of these widespread geochemicals are believed to be restricted to a limited number of diatoms, including Haslea ostrearia (and related species), Rhizosolenia setigera, and Pleurosigma intermedium. The unsaturation of the HBI alkenes ranges from 2-6 in different species and cultures. The number of stereogenic centres is usually limited to two in the HBI alkenes due to double bond positions. The relative and/or absolute configurations for these have been determined for a range of HBI alkenes produced from different diatoms cultured under a number of growth conditions. These determinations have involved a combined spectroscopic and chromatographic analysis using NMR spectroscopy and chiral gas chromatography, respectively. HBIs isolated from Haslea spp. belong to a specific structural type which exhibit configurational diastereoisomerism, while those isolated from P. intermedium and R. setigera represent a different structural type and usually exist as mixtures of geometric isomers only. HBIs are reported from a new species of diatom whose stereochemical properties lie between those found for Haslea spp. and P. intermedium.

Alkenes↗

PubMed2001

Tetra-unsaturated sesterterpenoids (Haslenes) from Haslea ostrearia and related species.

The structures and distributions of C25 highly branched isoprenoid (HBI) alkenes (Haslenes) have been determined following isolation from cultures of the diatoms Haslea ostrearia, Haslea crucigera, Haslea pseudostrearia and Haslea saltstonica. The distributions of the HBIs change between Haslea species and also between different cultures of the same species. Large scale culturing of H. ostrearia and H. pseudostrearia has enabled the structures of three new tetra-unsaturated alkenes to be determined by NMR spectroscopy. The structural relationships between different Haslenes together with the potential significance of the biosynthesis of HBIs by the Haslea genus is discussed.

Alkenes↗

PubMed2001

Effects of temperature on polyunsaturation in cytostatic lipids of Haslea ostrearia.

Unusual chemicals produced by the-'blue oyster' diatom, Haslea ostrearia, include the water-soluble blue pigment marennine and numerous polyunsaturated sesterterpene oils or haslenes. Aqueous extracts of the alga exhibit in vitro and in vivo activities against human lung cancer cells and anti-HIV effects. Here we report that three haslenes also demonstrate in vitro cytostatic action against a human lung cancer cell line. The most active haslene is the most unsaturated and unsaturation in the haslenes increases with increasing algal growth temperature.

Alkenes↗

PubMed2001

Factors influencing the distributions of polyunsaturated terpenoids in the diatom, Rhizosolenia setigera.

Polyunsaturated highly branched isoprenoid (HBI) hydrocarbon distributions of laboratory cultures of five strains of the planktonic diatom Rhizosolenia setigera (Brightwell) are shown herein to be highly variable. Some strains produced both haslenes with from three to five double bonds and rhizenes. The haslenes comprised not only Delta5 alkenes but also those with C7(20) unsaturation, including hasla-7(20),9E,Z, 23-trienes and hasla-7(20),9E,Z-13, 23-tetraenes. The rhizenes contained C7(25) unsaturation and the vinyl moiety common to all algal haslenes so far characterised. The effects of temperature and salinity on HBI composition, along with isotopic content, were determined in strain CS 389/A. Increase in growth temperature from 18 to 25 degrees C increased the degree of unsaturation in the haslenes and E to Z isomerisation in the triene. There was also an increase in unsaturation in the rhizenes at the highest growth temperature, with hexaenes dominant over the pentaenes but in the rhizenes, Z to E isomerisation increased. Increased salinity from 15 to 35 psu increased cell growth and rhizene production but decreased haslene production. Unsaturation in haslenes was not changed by increased salinity but unsaturation in the rhizenes decreased. These may reflect growth rate differences. The carbon isotopic compositions of the haslenes and rhizenes were similar to that of the major sterol at 18 degrees C, but the major HBI isomers were 3-4 per mil depleted relative to phytol released by saponification from chlorophyll a. This suggests biosynthesis of HBIs from a different isotopic pool of isopentenyl biphosphate to that from which phytol is biosynthesised. At 25 degrees C, further isotopic differences were observed. The variables controlling HBI distributions in R. setigera are still not fully understood and rationalisation of the environmental controls on the sedimentary distributions of the HBIs from R. setigera may only be possible once such factors are established.

Alkenes↗

PubMed2001

A simple method for SEM examination of sectioned diatom frustules.

We describe an innovative yet straightforward method to obtain high quality thin sections of diatom exoskeletons for observation by scanning electron microscopy (SEM). The use of this new technique allows for clear observations of some ultrastructural valve features, including the raphe, which are generally difficult to observe and describe accurately using transmission electron microscopy analysis of thin sections or SEM of randomly fractured diatom valves. In addition, because this method involves the complete removal of the organic content of the diatom cells, resulting in clean and mostly undisturbed skeletal thin cross-sections, even the intact valvar structures of weak girdle bands can be studied.

Diatoms↗

PubMed2001

Synthesis of N-pyridinyl(methyl)-1,2-dihydro-4-hydroxy-2-oxoquinoline-3-carboxamides and analogues and their anti-inflammatory activity in mice and rats.

The topical anti-inflammatory activity of a series of N-pyridinyl(methyl)1,2-dihydro-4-hydroxy-2-oxoquinoline-3-carboxamides, analogues of roquinimex, has been evaluated by measuring their inhibitory effect in the phorbol myristate acetate (PMA)-induced mouse ear swelling test, used as a screening test. All the eight carboxamides tested (9-16) exhibited significant inhibitory activity at 0.4 and 0.2 mM kg(-1). The most potent compound, the 6-bromo derivative 12, induced a 73% inhibition at 0.2 mM kg(-1). Pharmacomodulation was carried out by heterocycle opening and molecular simplification leading to pentafluorobenzoylacetamide 17, pentafluorocinnamamides 18 and 19, and pentafluorobenzaldimines 20 and 21. All the five compounds exerted a reduction in swelling (49-63% at 0.2 mM kg(-1)) comparable with ibuprofen (56%). Anti-inflammatory activity of the most efficient compounds was evaluated by carrageenan-induced rat paw oedema inhibition. The pentafluorobenzaldimine 20 showed the highest activity with an inhibition percentage of 85% at 0.2 mM kg(-1).

Animals↗

PubMed2000

Continuous marennin production by agar-entrapped Haslea ostrearia using a tubular photobioreactor with internal illumination.

The marine diatom Haslea ostrearia was immobilized in a tubular agar gel layer introduced into a photobioreactor of original design with internal illumination for the continuous synthesis of marennin, a blue-green pigment of biotechnological interest. Marennin was produced for a long-term period (27-43 days) and the volumetric productivity was maximum (18.7 mg day(-1) l(-1) gel) at the highest dilution rate (0.25 day(-1)) and lowest agar layer thickness (3 mm). Heterogeneous cell distribution in the agar layer revealed diffusional limitation of light and nutrients. However, the 3 mm gel thickness led to a more homogeneous cell distribution during incubation and to an increase of the whole biomass in the agar gel layer.

Agar↗

PubMed2000

Configurations of polyunsaturated sesterterpenoids from the diatom, Haslea ostrearia.

The partial configurations of C25 isoprenoid alkenes isolated from the diatom Haslea ostrearia Gaillon (Simonsen) have been established. A combination of NMR spectroscopy studies of the alkenes with chiral shift reagents in conjunction with soluble silver beta-diketonate complexes and enantioselective gas chromatography of oxidation products of the alkenes was used. Unexpected differences in highly branched isoprenoid isomer configurations were observed between different laboratory cultures of the alga.

Alkenes↗

PubMed2000

Synthesis and antileishmanial activity of new 1-(pyridin-2-yl)imidazolidin-2-ones derived from 2-amino-4,6-dimethylpyridine.

Derivatives of 2-amino-4,6-dimethylpyridine resulting from the integration of the amino function into a 2-imidazolidinone were synthetized via the corresponding 2-chloroethylurea. N3-benzylation, acylation or sulfonylation afforded the target compounds 6-14 which were evaluated for their in vitro and in vivo antileishmanial activity. Two compounds, the N3-benzyl derivative 7 and the N3-tolylsulfonyl derivative 14, exhibited potent inhibition against cultured extracellular promastigotes of Leishmania mexicana with IC50 comparable to that of the previously studied N-(4,6-dimethylpyridin-2-yl) furan-2-carboxamide 2: 32.4, 46 and 69 mumol/l, respectively. Experimentation of their activity against mice macrophage amastigotes pointed out that IC50 of imidazolidones 7 and 14 were 7 and 13-fold lower than that of amide 2: 13.7 and 89 mumol/l. In vivo evaluation in Balb/c mice, intradermally infested with Leishmania mexicana, confirmed that, in the lesion site, compound 14 was able to significantly reduce the parasite burden at a daily i.p. dose of 10 mg/kg. It was demonstrated that these N-pyridinylimidazolidinones could act by interference with the parasite PLA2 activity.

Animals↗

PubMed1999

Effects of shear on two microalgae species. Contribution of pumps and valves in tangential flow filtration systems.

The circulation of microorganisms in tangential flow filtration systems induces perturbations and then the damage of brittle cells. This work is focused on the shearing of two marine microalgae species (Skeletonema costatum and Haslea ostrearia), both largely cultivated in western France (Région des Pays de la Loire). We have studied the effects of the circulation of these cells in pumps and valves. For the pumps, it is shown that shear stress is due to the type of pump, but that mechanical shear can have different effects even if the pumps and the number or frequency of loops are the same. Hence other intrinsic parameters of the pump must be taken into account: rotating velocity (omega), capacity (Cyl = output flow/rotating velocity) or internal leakage (K = inner volume/capacity). In throttling valves, the aim is to correlate the effect of shear to a parameter related to the inner geometry of the valve and to operating conditions. An overall parameter is then evaluated: the pressure drop coefficient Kv which integrates both the type of valve (ball valve or globe valve type) and its opening degree. Kv is derived from the relationship DeltaH = Kvu2/2g. The modelling of the shear effects is now conceivable: basic descriptive data used so far (type of pump, geometry or opening degree of the valve, etc.) being completed and partially substituted by quantitative parameters (rotating velocity, capacity, or internal leakage for the pumps, Kv coefficient for the valves).

Biomass↗

PubMed1999

New selective nonsteroidal aromatase inhibitors: synthesis and inhibitory activity of 2,3 or 5-(alpha-azolylbenzyl)-1H-indoles.

Six azolyl substituted indoles were synthesized and tested for their activity to inhibit two P450 enzymes: P450 arom and P450 17a. It was observed that the introduction of alpha-imidazolylbenzyl chain at carbon 3 or 5 on indole nucleus led to very active molecules. Compounds 22, 23 and especially 33 demonstrate very high potential against P450 arom. Under our assay conditions of high substrate concentration the IC50 are 0.057, 0.0785 and 0.041 microM, respectively. These compounds are moderate inhibitors against P450 17alpha.

Aromatase Inhibitors↗

PubMed1999

Monitoring of labile zinc in cultures of Skeletonema costatum using a salt groundwater.

Labile Zn concentration was monitored by differential pulse anodic stripping voltammetry (DPASV) throughout the exponential growth phase of the marine diatom Skeletonema costatum (Grev.) Cleve. Algal blooms were induced both under natural conditions and in laboratory experiments using a salt groundwater (salinity 33) from the Bay of Bourgneuf, northwest coast of France. Salt groundwater is a very complex medium containing high concentrations of dissolved organic matter and other trace metal adsorbents, such as phosphate, iron oxyhydroxides, and manganese and silicon oxides, which can bind metal ions, reducing their availability and toxicity to algae. Besides metal uptake by algae and complexation of Zn by algal exudates, the rapid decrease in the labile Zn concentration during the algal blooms was ascribed mainly to the adsorption or coprecipitation of Zn ion onto freshly formed iron hydroxides.

Cations↗

PubMed1999

Antiviral and anticoagulant activities of a water-soluble fraction of the marine diatom Haslea ostrearia.

A water-soluble fraction from the marine diatom Haslea ostrearia was capable to inhibit the in vitro replication of HSV-1 in Vero cells with 50% inhibitory concentration (EC50) of 14 micrograms/ml at a multiplicity of infection of 0.01 ID50/cells. In addition, this fraction delayed the HIV-1-induced syncitia formation on MT4 cells. At concentrations up to 200 micrograms/ml, no cytotoxicity was observed for both the Vero and MT4 cells. The fraction only inhibited the blood coagulation process at concentrations considerably exceeding the EC50.

Animals↗

PubMed1997

Genealogical study of oculopharyngeal muscular dystrophy in France.

This work is based on 54 probands affected by oculopharyngeal muscular dystrophy (OPMD). The muscle biopsy of all these patients showed the presence of the intranuclear inclusions, specific of this disease. The residence of the probands is concentrated in three clusters: the Paris, Marseilles and Bordeaux regions. The genealogical study was carried out on 43 probands, 10 of which did not have any ascendance in France for more than two generations. The geographic origin of the 33 patients of French descent was distributed over numerous regions, not including the Paris and Marseilles regions where many patients lived. This geographic dispersion and the rarity of common genealogies of the probands, did not suggest the existence of a recent founder effect, in contrast to what is observed in the French-Canadian community. The existence of a link between French and French-Canadian families is currently being investigated.

Family Health↗

PubMed1997

Harmonic imaging of porcine intraovarian arteries using sonographic contrast medium: initial findings.

The purpose of this study was to visualize, using harmonic gray-scale imaging, blood flow in porcine intraovarian arteries after intravenous injections of a bubble-based sonographic contrast medium. Five female pigs underwent laparotomy. Surgically isolated ovaries were scanned intraperitoneally by an ultrasound system reconfigured with software changes to accomplish harmonic imaging. The transmission and receiving frequencies were set at 3.75 and 7.5 MHz, respectively. After injection of the sonographic contrast medium (Aerosomes) into a peripheral vein, the ovaries were imaged in the harmonic mode. Ten minutes later, another contrast injection was administered and conventional gray-scale imaging of the ovary performed. In all five pigs, intraovarian arteries were clearly identified upon harmonic imaging as brightly echogenic moving columns. The arterial blood pool appeared brighter during systole than diastole. Upon ultrasound contrast-assisted conventional gray-scale imaging, intraovarian arteries were not visualized in four pigs and poorly visualized in one. We conclude that contrast-assisted harmonic imaging can adequately visualize blood flow in intraovarian arteries of surgically exposed porcine ovaries. Clinically, harmonic imaging may facilitate early detection of tumor-induced angiogenesis in the human ovary.

Animals↗

PubMed1997

Carotid artery volume flow: in vivo measurement with time-domain-processing US.

PURPOSE: To evaluate carotid artery volume-flow measurements with time-domain-processing ultrasonography (US). MATERIALS AND METHODS: Volume-flow measurements were obtained in the carotid arteries of nine swine with time-domain-processing US. Four swine were prepared with a model of an arteriovenous shunt. Flow through the carotid artery was varied by means of a number of physiologic and pharmacologic interventions. The reference standard for volume flow consisted of measurements with transit-time US flowmetry. At a limited number of measurement points, this reference standard was validated against true volume flow measured with timed collection. RESULTS: For flow rates less than 500 mL/min, a linear correlation existed between measurements with time-domain processing and the US flow meter (r2 = .96, P < .001, slope = 1.117). Values above 500 mL/min were less well correlated with the reference standard. True flow was underestimated with both methods, less so with time-domain processing than with US flowmetry (underestimation, 10% versus 21%). Measurements were significantly less reproducible with time-domain processing than with US flowmetry (P < .001). Interobserver variability was negligible. CONCLUSION: Because of operator errors, measurements with time-domain processing should be repeated at least three times to ensure accuracy and may be inaccurate in flow rates over 500 mL/min.

Animals↗