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Biomedical subjects

J C Debouzy

Publications and source records attributed to J C Debouzy.

36 records · Page 2Linked to original sources
PubMed1997

[Study by NMR of the modifications of brain lipid composition related to the tumor processes].

1H, 13C, 31P and 14N NMR spectroscopies were used to investigate the lipid composition of brain tumors (GL6 glioma) in rats, by comparison with controlateral hemispheres. Comparative indexes derived from NMR signal intensities were used to establish the statistical analysis. It was found that sterol metabolism and sphingolipid/glycerolipids ratio are significantly modified when a tumor is present.

Animals↗
PubMed1997

NMR study of per(3,6-anhydro) alpha cyclodextrin as a potential agent for the biological decontamination of lead.

The ability of per(3,6-anhydro) alpha cyclodextrin(3,6CD) to capture lead from a preformed glutathion (GSH)-lead complex was investigated by NMR spectroscopy. Such a removal strongly depends on the nature and pH of the buffer used in the competition experiments. It was found that an almost complete removal of lead can be achieved at pH 5.5, especially when lead nitrate is used. The capture also strongly depends on the nature of the lead species as well as of the counter ion present in the medium. These observations imply that decontamination of lead by this process should be optimal under acidic conditions, i.e. in the acidic tractus (stomach). Conversely, lead decontamination at neutral pH was of poor efficiency or required a large excess of (3,6CD). This was particularly the case when human plasma was used as solvent.

Chelating Agents↗
PubMed1996

Interactions of inorganic mercury with phospholipid micelles and model membranes. A 31P-NMR study.

The binding of inorganic mercury Hg(II) to phospholipid headgroups has been investigated by phosphorus-31 nuclear magnetic resonance of phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylcholine (PC) in water micellar and multilamellar phases. HgCl2 triggers the aggregation of phospholipid micelles, leading to a lipid-mercury precipitate that is no longer detectable by high-resolution 31P-NMR. The remaining signal area corresponds to micelles in the soluble fraction and is a non-linear function of the initial mercury-to-lipid molar ratio. Kinetics of micelle aggregation are exponential for the first 15 min and show a plateau tendency after 120 min. Apparent Hg(II) affinities for phospholipid headgroups are in the order: PE > PS > PC. The same binding specificity is observed when HgCl2 is added to (1:1) mixtures of different micelles (PE + PC; PS + PC). However, mercury binding to mixed micelles prepared with two lipids (PE/PC or PS/PC) induces the aggregation of both lipids. Hg(II) also leads to a 31P-NMR chemical shift anisotropy decrease of PC, PS and mixed (1:1) PE/PC multilamellar vesicles and markedly broadens PS spectra. This indicates that HgCl2 binding forces phospholipid headgroups to reorient and that the concomitant network formation leads to a slowing down of PS membrane collective motions. Formation of a gel-like lamellar phase characterized by a broad NMR linewidth is also observed upon HgCl2 binding to PE samples both in fluid (L alpha) or hexagonal (H(II)) phases. The PE hexagonal phase is no longer detected in the presence of HgCl2. Mixed PE/PC dispersions remain in the fluid phase upon mercury addition, indicating that no phase separation occurs. Addition of excess NaCl leads to the appearance of the non-reactive species HgCl4(2-) and induces the reversal of all the above effects.

Binding Sites↗
PubMed1996

Synthetic pyridopurines derived from food pyrolysis products: intercalation, interactions with membranes, cyclodextrin complexation, and biological mitogenic properties.

Crucial conditions for the pharmacological use of active compounds are their ability to cross the biological barriers and reach their intracellular target. In the case of two antiviral pyridopurine derivatives, 1 and 2, this included essentially the membranes and the nucleic acids. Thus the interactions of 1 and 2 with model membranes and oligonucleotides were studied using NMR spectroscopy. It was found that these hydrophobic molecules can be incorporated into the model membranes at the terminal methyl group level, inducing dynamic perturbations in the bilayer. In the presence of the synthetic oligonucleotide ACATGT, both molecules can intercalate aspecifically in AT and GC systems. Inclusion complexes of 1 and 2 beta-cyclodextrins with a 1:1 stoichiometry, were also prepared. This led to to propose two galenic forms 1 and 2, i.e. included in phospholipid vesicles in the form of a beta-cyclodextrin complex

Amines↗
PubMed1996

Imidazo[1,2-a]pyridine derivatives as antiviral agents: biological assays and NMR study of their interactions with membranes and oligonucleotides.

Three potentially antiviral imidazo[1,2-a]pyridine derivatives of increasing hydrophilicity were tested in their interactions with model membranes and synthetic oligonucleotides. It was shown that the most hydrophobic derivative [1], located in the depth of the bilayer only induces minor membrane damages. The molecule [2], only poorly hydrophobic, integrates also the bilayer in the medium part of the chains while the most hydrophilic [3] exhibits fluidizing and slightly detergent properties. In the presence of synthetic oligonucleotide ACATGT no intercallation of the three derivatives was evidenced. By considering their antiviral activity in the absence of evident mitogenic properties, another mechanism of action was proposed.

Antiviral Agents↗
PubMed1995

[NMR study of membrane incorporation of cysteamine].

The incorporation of the cysteamine molecule in small unilamellar vesicles was studies using proton NMR technics. A linear inclusion of the radioprotective molecule was firstly observed by increasing the Cysteamine/phospholipid molar ratios, followed by a saturation for the highest ratios. Such results may be adapted to a new galenic form study.

Cysteamine↗
PubMed1995

[Interaction between 4-hydroxynonenane with membrane system. 1H, 31P, 2H NMR study].

The interactions between membranes and 4-hydroxynonenane (HNE)-a natural product of polyinsatured fatty acids peroxidation-were investigated by NMR spectroscopies. This molecule is located in the intermediate part of the bilayer. The presence of the HNE induces an increase of the fluidity in the deep part of the membrane, while a rigidification of the superficial part is found.

Aldehydes↗
PubMed1994

[Demonstration of molecular combinations of alpha cyclodextrin (ACD) with dioctanoyl glycerol].

The molecular association of dioctanoyl glycerol (DOG) with the natural alpha cyclodextrin molecule (ACD) was studied using small unilamellar vesicles (SUV) by proton and 13C NMR. While no classic inclusion complex was found, a molecular association exists, leading to the formation of an insoluble precipitate. The possibility of a polar head group implication is discussed about the dimyristoyl phosphatidyl choline model.

Cyclodextrins↗
PubMed1994

Naphtyl methyl imidazoline (NMI) membranes interactions: NMR study and evaluation of possible radioprotective consequences.

The interactions of the radioprotective molecule Naphtyl methyl imidazoline (NMI) with membranes have been studied using biophysical and biochemical methods. 1H, 2H and 31P-NMR methods showed a strong interaction with the deep part of the layer of model membranes inducing the formation of a new membrane compartment. These properties are not involved in the radioprotection effect of NMI which is more probably due to its vasoconstrictive properties.

Humans↗
PubMed1992

Interaction of the malonyldialdehyde molecule with membranes. A differential scanning calorimetry, 1H-, 31P-NMR and ESR study.

The membrane interactions of malonyldialdehyde (MDA), natural product of polyunsaturated fatty acids peroxidation were investigated by differential scanning calorimetry, and ESR or NMR spectroscopy. This component is located in the superficial part of the bilayer, where it increases the local fluidity. High concentrations of MDA induce major membrane damage. Similar consequences of MDA-membrane interactions were observed on erythrocyte ghosts.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1991

Lipophilic glycosyl phosphotriester derivatives of AZT: synthesis, NMR transmembrane transport study, and antiviral activity.

Phosphate derivatives of AZT esterified with a carbohydrate (D-glucose, D-mannose, and ethyl D-mannopyranoside) and a hexadecyl chain were prepared from glucose 6-phosphate and D-mannose precursors. The 31P NMR study of the mannosyl phosphotriester series in the presence of large unilamellar vesicles demonstrated either an interaction with the external lipid layer or a transmembrane transport into the intravesicular interface. The antiviral activity, measured by the inhibition of cytopathogenicity on different infected cells and of reverse transcriptase activity in the supernatant of cultures, appeared to be comparable to that of AZT, in the micromolar range.

Antiviral Agents↗
PubMed1990

Glucosyl phosphotriesters of nucleosides: exchange mechanism of transmembrane transport and application to 5-fluoro-deoxyuridine.

The structure and membrane interactions of lipophilic glucosyl phosphotriester derivatives of thymidine and 5-fluoro-deoxy thymidine are investigated by NMR spectroscopy. The self-association of these molecules, found in different solvents, presents a diastereoisomeric effect which is also observed in the transmembrane transport inside large unilamellar vesicles. The influence of the hydrophobic chain and the nature of the nucleoside in the water-membrane exchange process is discussed.

Biological Transport↗
PubMed1989

Ajoene, the antiplatelet compound derived from garlic, specifically inhibits platelet release reaction by affecting the plasma membrane internal microviscosity.

Ajoene (E,Z-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), a product of the rearrangement of allicin (a major component of raw garlic), has been shown to be a potent inhibitor of platelet aggregation in vitro through inhibition of granule release and fibrinogen binding. Our present study further elaborates on this inhibitory action, through studies of the effect of ajoene on the earliest steps of platelet activation. The transducing mechanism involved in thrombin-induced platelet activation was not modified by the drug as indicated by a normal breakdown of phosphatidylinositol 4,5,bisphosphate and normal production of phosphatidic acid. Likewise, the agonist-induced phosphorylation of myosin light chain (P20) and of the 43 kD protein (P43) were not impaired by ajoene. Under the same conditions, however, ajoene (100 microM) produced a strong inhibition of the thrombin-induced release of dense body and alpha-granule constituents. Electron spin resonance studies of the effect of ajoene on some physico-chemical properties of the platelet plasma membrane (intact platelets), as well as on artificial lipid membranes, indicated that ajoene increased mobility of the fatty acid spin label 16 nitroxide stearate. This suggests the existence of a decreased microviscosity of the most internal region within the lipid bilayer membrane, without affecting the outer hydrophilic moieties of the bilayer. As a whole, these results suggest that the effect of ajoene on the release reaction must be, in part, due to physical modification of the bilayer, which impairs the fusion of the granules and plasma membrane, a prerequisite for exocytosis.

Blood Platelets↗
PubMed1989

Measurement of an intracellular pH rise after fertilization in crab eggs using 31P-NMR.

The effect of fertilization upon the intracellular pH, pHi, in crab ovulated eggs was examined by 31P-NMR. The pHi values were obtained from the chemical shift differences between the phosphoarginine PA resonance and the inorganic phosphate Pi resonance. The detection of the Pi peak was accomplished by Hahn spin-echo experiments in order to cancel the broad signal arising from phosphoproteins which overlaps the Pi signal. The average pHi of the unfertilized unactivated eggs was 6.55 and a rise of 0.12 pH unit occurred after fertilization.

Animals↗
PubMed1989

Interaction of antiaggregant molecule ajoene with membranes. An ESR and 1H, 2H, 31P-NMR study.

The structure of ajoene, a molecule extracted from garlic, has been studied by 1H-NMR and its interaction with model membranes by 1H-, 2H-, 31-P-NMR and ESR experiments. This study clearly shows that the ajoene molecule is located deep in the layer and is close to the interlayer medium. Moreover while NMR experiments show that the membrane structure is only slightly affected by the presence of ajoene, ESR experiments reveal significant modifications in phospholipid dynamics. This interaction, observed before with the phenothiazine derivative, promazine, results in an increase of the membrane fluidity in its hydrophobic part and could be related to clinical properties of ajoene.

Deuterium↗
PubMedDate not supplied

Is uranyl scavenger hexakis(3,6-anhydro) tetrakis(2A,B,D,E-O-octyl) cyclomaltohexaose (OCT) relevant with biosystems?

Hexakis(3,6-anhydro)tetrakis(2A,B,D,E-O-octyl) cyclomatohexaose (OCT) has been recently shown as a powerful cryptant for lead, mercury, and especially for uranyl. As previous results have been obtained in an organic solvent (methanol), a similar evaluation of OCT complex formation was achieved in aqueous medium and in the presence of membrane-mimicking systems such as phospholipid vesicles, liposomes and micelles. It was found that OCT, while completely insoluble in water, forms solid gel structures when in equimolar mixtures of water and methanol. Moreover, OCT exhibits detergent properties. Finally, OCT was successfully introduced in detergent solutions while keeping. Uranyl complexing properties. Possible applications of such models were also discussed.

Chelating Agents↗
PubMedDate not supplied

1H-NMR study of heavy metals complexation with hexakis(3,6-anhydro) tetrakis(2A,B,D,E-O-octyl) cyclomaltohexaose (OCT).

The selection of the cations bound by hexakis (3,6-anhydro) tetrakis (2A,B,D,E-O-octyl) cyclomatohexaose (OCT) was performed by thin layer chromatography. The three cations selected, UO(2)2+, Pb2+ and Hg2+ were then studied by 1H-NMR. A 2:1 OCT/cation stoichiometry was identified in the cases of UO(2)2+ and Pb2+. While UO(2)2+ binding (logK around 6) followed a fast exchange kinetics, a slow or intermediate complexation was found with Pb2+ (logK = 5.6) and Pb2+, respectively. In the latter case, the poor solubility of Hg2+ precluded to propose neither a stoichiometry nor an estimation of the affinity constant.

Chelating Agents↗