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Biomedical subjects

A Astier

Publications and source records attributed to A Astier.

At least 19 recordsLinked to original sources
PubMed2006

[New drug formulations for cancer therapy].

Despite recent emergence of novel therapeutic agents the major progress achieved in cancer treatments results from conventional drugs used for cytotoxic or hormone therapy. Over the past 20 years, a more rational and more pharmacological-based approach to chemotherapy has led to major successes. One of the most promising avenues of research is to improve the pharmacokinetic properties of well-known anticancer drugs (bioavailability, distribution, targeting, drug carriers) by modifications of their formulations (new drug delivery systems). As an example, new pharmaceutical forms of analogs of LH-RH, (microparticles or implants) permitting sustained release of the drug for months, are now largely used in the routine chemotherapy for prostate cancers. Improvement of the oral bioavailabilty of drugs previously administered only by the parenteral route is simplifying treatment protocols. Parenteral delivery of doxorubicine entrapped in liposomes (pegylated liposomes) decreases the cardiotoxicity and increases the half-live of this drug widely used in the treatment of breast carcinomas. Molecular targeting using immunocarriers such as immunoliposomes is also a very strong field of research.

Antineoplastic Agents↗
PubMed2005

Excitation energies of superdeformed States in 196Pb: towards a systematic study of the second well in Pb isotopes.

The excitation energy of the lowest-energy superdeformed band in 196Pb is established using the techniques of time-correlated gamma-ray spectroscopy. Together with previous measurements on 192Pb and 194Pb, this result allows superdeformed excitation energies, binding energies, and two-proton and two-neutron separation energies to be studied systematically, providing stringent tests for current nuclear models. The results are examined for evidence of a "superdeformed shell gap."

Journal Article↗
PubMed2005

Evaluation of skin viscoelasticity in type 1 neurofibromatosis patients.

Neurofibromatosis type 1 (NF1) is a frequent autosomal dominant disease characterized by cutaneous benign tumors called neurofibromas. Surgery takes an important place in managing these skin disorders. However, skin distensibility and softness of NF1 patients quickly offset the surgical benefit. The aim of this study was to determine the rheological behavior of neurofibromas and compare it with healthy skin in an attempt to comprehend what leads to this phenomenon. Thirty patients were admitted to this study. A group of 24 healthy control subjects was also included. The skin elasticity was assessed by a noninvasive in vivo suction device (Cutometer) including 5 consecutive suctions. The assessments were performed on neurofibroma skin, the supposedly healthy skin around neurofibromas and the healthy skin of control subjects. The extensibility at the first and the fifth traction in NF1 patients (neurofibromas and the supposedly healthy skin around it) was significantly different compared to the healthy skin of control subjects. The viscoelastic parameters obtained from the neurofibromas were significantly different in comparison to those obtained from the supposedly healthy skin of NF1 patients and the healthy skin of control subjects. The rheological profiles of the neurofibromas and the apparent healthy skin of NF1 patients demonstrated a hyperextensibility behavior, but in neurofibromas, the skin was unable to return to its initial position at the end of the stretch.

Adolescent↗
PubMed2004

Evaluation of the new heterogeneous ACMIA immunoassay for the determination of whole-blood cyclosporine concentrations in bone marrow, kidney, heart, and liver transplant recipients.

Cyclosporine (CyA) has a narrow therapeutic index. Determination of CyA concentrations correlate with rejection or adverse effects like nephropathy. Cyclosporine is assayed based on either chromatographic or many different immunoenzymologic techniques. The investigators evaluated a new heterogeneous immunoassay of CyA on RxL Dimension. The pretreatment step is automatically performed in the apparatus. Linearity, intra- and interday precision, limit of quantification, dilutions, and stability of the equipment were compared with the EMIT method for patient determinations. The heterogeneous immunoassay showed a good linearity between 0 and 500 ng/mL, and intra- and inter-day precision with a coefficient of variation below 9.2%. The investigators observed reproducible and accurate dilutions of high concentrations (500 to 2000 ng/mL). The correlation with the EMIT technique was valid: ACMIA = 0.964 EMIT + 0.156 (r = .96) for different types of transplant (n = 116). Finally, this new system improves the determination of CyA concentrations.

Bone Marrow Transplantation↗
PubMed2004

TGFbeta-mediated activation of Smad1 in B-cell non-Hodgkin's lymphoma and effect on cell proliferation.

We have previously reported an overexpression of Smad1 in follicular lymphoma (FL) cells, which are characterized by the t(14;18) bcl2/IgH translocation. Smad1 is commonly involved in bone morphogenetic protein but not in tumor-transforming growth factor beta (TGFbeta) signaling pathways. This study focuses on Smad1 signaling pathway in non-Hodgkin lymphoma cells including follicular or large-cell lymphoma cells. Our results support the notion that phosphorylation of Smad1 is mediated by TGFbeta present in the microenvironment and occurs in FL in vivo. Using an in vitro coculture system mimicking interactions between stroma cells and FL cells, we found that both the cell partners release TGFbeta at a sufficient concentration to activate Smad pathways in the malignant cells. This Smad1 activation involves TGFbetaRII but not ALK-1 receptors, and does not compete with the Smad2 pathway. Moreover, proliferation assays performed on lymphoma cells expressing wild-type or mutated Smad1, or in which endogenous Smad1 level was decreased by gene silencing, strongly supported that overexpression and activation of Smad1 modifies the biological response of lymphoma B cells to TGFbeta family members. This work opens new insights into aberrant Smad pathways and their pathophysiological role in FL and in other non-Hodgkin lymphomas.

Activin Receptors, Type I↗
PubMed2003

Atovaquone-loaded nanocapsules: influence of the nature of the polymer on their in vitro characteristics.

Nanocapsules with atovaquone concentration of 1,000 micrograms/ml were prepared according to the interfacial deposition technique using different polymers: poly- epsilon -caprolactone (PECL), poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLAGA). The following characteristics of nanoparticles were determined: percentage of encapsulation of atovaquone, percentage of encapsulation of benzyl benzoate (BB), nanoparticle size, nanoparticle wall thickness, suspension pH, and in vitro stability. The different formulations showed similar characteristics: maximal percentage of encapsulation (100%), particle size of approximately 230 nm, neutral pH and wall thickness of approximately 20 nm. The type of polymer used was the main factor influencing stability, in decreasing order: PECL>PLA>PLAGA. No release of atovaquone or benzylbenzoate was noted with PECL nanoparticles over 4 months. Release of atovaquone (25.9%) was found with PLA nanoparticles at 4 months. Release of both atovaquone (18.9%) and benzylbenzoate (54.2%) was noted with PLAGA nanoparticles from the third month, indicating a disruption of the nanoparticle membrane.

Antiprotozoal Agents↗
PubMed2003

Therapeutic evaluation of free and nanocapsule-encapsulated atovaquone in the treatment of murine visceral leishmaniasis.

The activities of free atovaquone (ATV) and of poly(D,L-lactide) nanocapsules loaded with the drug, in the treatment of mice with visceral leishmaniasis caused by Leishmania infantum, were compared. Each mouse was infected intravenously with 2x10(7) promastigotes, on day 0. On days 15, 17 and 19, most of the infected mice were treated either with free ATV, in a dimethylsulphoxide/cremophor/water mixture, or with the ATV-loaded nanocapsules (at, respectively, 0.2-1.6 and 0.125-1.0 mg ATV/kg, on each treatment day). The rest of the mice were left untreated, as controls. All the mice were killed on day 21 and dissected so that their livers and spleens could be weighed. The liver parasite burdens, evaluated using the Stauber method, indicated that the ATV-loaded nanocapsules were significantly more effective than the free drug. In nanocapsules, for example, a total dose of 3.0 mg ATV/kg reduced liver burdens by 71.3%, whereas treatment with a higher total dose of the free drug (4.8 mg/kg) only cut the number of liver parasites by 34.4%. The dose-response data indicated that livers would have been cleared of parasites if the nanocapsule preparation had been given as three doses each equivalent to 3 mg ATV/kg, whereas the maximum suppression possible with the free drug would have been about 61%, whatever the dose.

Animals↗
PubMed2002

(68)(28)Ni(40): Magicity versus superfluidity.

The neutron-rich (66,68)Ni have been produced at GANIL via interactions of a 65.9A MeV 70Zn beam with a 58Ni target. Their reduced transition probability B(E2;0(+)(1)-->2+) has been measured for the first time by Coulomb excitation in a (208)Pb target at intermediate energy. The B(E2) value for (68)Ni(40) is unexpectedly small. An analysis in terms of large scale shell model calculations stresses the importance of proton core excitations to reproduce the B(E2) values and indicates the erosion of the N = 40 harmonic-oscillator subshell by neutron-pair scattering.

Journal Article↗
PubMed2002

Characterisation of atovaquone resistance in Leishmania infantum promastigotes.

Atovaquone, an antiparasitic agent, could possibly represent an alternative therapy after relapse following classical treatment for visceral leishmaniasis. Atovaquone-resistant strains were selected in vitro by stepwise drug pressure to study the mechanism of resistance in Leishmania. Characteristics of a promastigote strain resistant to 250 microg/ml of atovaquone were compared with those of the wild type (WT) strain. Resistant strains were shown to have a high level of resistance (45 times). They were stable in drug-free medium for 6 months, and showed no cross-resistance with other antileishmanial drugs. Rhodamine uptake and efflux were studied. They were not modified in the resistant strain, indicating the absence of P-glycoprotein overexpession. The effect of atovaquone on membrane lipidic composition was determined in both WT and atovaquone-resistant promastigotes. Analysis of lipid composition of the atovaquone-resistant strain showed that sterol biosynthesis was decreased in atovaquone-resistant parasites. Cholesterol was found to be the major membrane sterol as opposed to the WT strain. Cholesterol, due to its ordering effect, could decrease membrane fluidity and subsequently block the passage of atovaquone through the membrane. Increased membrane cholesterol content and altered drug membrane fluidity resulted from possible decrease of ergosterol biosynthesis by atovaquone, incorporation of cholesterol by promastigotes in the culture medium, solubilisation of atovaquone by cholesterol and co-passage of the two compounds or influence of dimethylsulfoxide. These results indicate that different cellular alterations may participate in the resistant phenotype, by altering drug membrane permeability.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Linear polarization measurement of interband transitions in superdeformed 190hg: model-independent evidence for octupole vibrational structures.

The linear polarization of gamma rays between excited and yrast superdeformed (SD) states in 190Hg was measured using the four-element CLOVER detectors of the EUROBALL IV gamma-ray spectrometer. This measurement shows in a model-independent way that the interband transitions which compete with the highly collective in-band quadrupole transitions are largely enhanced electric dipoles. Not only do these results represent the first measurement of the multipolarity of transitions between different SD states, but they also provide strong evidence for the interpretation of the structures in the SD minimum of the A approximately 190 region in terms of octupole excitations.

Journal Article↗
PubMed2001

Treatment of methanol and isopropanol poisoning with intravenous fomepizole.

CASE REPORT: We report a case of mixed methanol and isopropanol poisoning in a patient who refused dialysis but agreed to treatment with intravenous fomepizole. The patient was asymptomatic on arrival, with initial blood methanol and isopropanol concentrations of 146 mg/dL and 39 mg/dL, respectively. Blood ethanol was undetectable. The patient was treated with fomepizole twice daily intravenously until blood methanol was undetectable. No side effects of therapy, other than transient eosinophilia, were observed. The evolution was uneventful and no metabolites of either alcohol were detected at any time during the hospitalization. The decay of plasma methanol and isopropanol under fomepizole treatment were well described by first-order kinetics. The plasma elimination half-lives of methanol and isopropanol were 47.6 hours and 27.7 hours, respectively. Fomepizole appears to have been effective in blocking the toxic metabolism of both methanol and isopropanol and was associated with a favorable outcome.

2-Propanol↗
PubMed2001

[Evaluation of the quality drug prescription for patients to be discharged from a university teaching hospital: statutory aspects].

The aim of this work was to assess the quality of written drug prescriptions for patients to be discharged from our hospital. The pharmacological pertinence was not evaluated. Each statutory mention was noted according to a binary system: 1=mention present, 0=mention not present. The total note after analysis of 308 drug prescriptions was 7.3 +/- 1.3 (3.3-10) for a 3.1 +/- 1.0 (1-10) for each prescription. Concerning the "physician" note, the average was 8.1 +/- 1.8. Nevertheless, the function and the name were quite ofently omitted (1/2 and 1/3 respectively). The lowest note was obtained for mentions relating to the patient [5.8 +/- 2.0 (0-10)]. The age and the name were omitted (9/10 and 1/10 respectively). The "drug" note was closed to total note and represented 7.5 +/- 1.8 (2-10). The detailed analysis showed that 1.8% of drug prescriptions presented an illegible drug name. The dosage form was not specified (1/2), the galenic form (1/3), the schedule (1/3) and the posology (1/5). These omissions did not have any serious repercussion as they were rectified in futher control steps. Nevertheless, educational and corrective measures could be aimed to improve the drug prescription.

Documentation↗
PubMed2000

Cutting edge: CD46, a new costimulatory molecule for T cells, that induces p120CBL and LAT phosphorylation.

The widely expressed transmembrane molecule CD46 is the complement regulatory receptor for C3b as well as the receptor for several pathogens. Beside its binding functions, CD46 is also able to transduce signals. We showed that CD46 aggregation on human T cells induces p120CBL and linker for activation of T cells (LAT) phosphorylation. These two proteins are adaptor proteins known to regulate TCR signaling. p120CBL is a complex adaptor protein involved in negatively regulating signaling events, whereas LAT is a transmembrane adaptor protein found in glycolipid-enriched microdomains essential for T cell activation. Therefore, we investigated if a CD46/TCR costimulation would affect T cell activation. Indeed, CD46/CD3 costimulation strongly promotes T cell proliferation. Therefore, we propose that CD46 acts as a potent costimulatory molecule for human T cells.

Adaptor Proteins, Signal Transducing↗
PubMed2000

The preparation and evaluation of poly(epsilon-caprolactone) microparticles containing both a lipophilic and a hydrophilic drug.

An original dosage form for oral delivery based on the encapsulation of both, lipophilic and hydrophilic drugs, in poly(epsilon-caprolactone) (PCL) microparticles prepared either by the oil-in-water (o/w) or the water-in-oil-in-water (w/o/w) solvent evaporation method was developed. Microparticles were characterized in terms of morphology, size, encapsulation efficiency and drug release. The physical state of the drugs and the polymer was determined by scanning electron microscopy (SEM), X-ray powder diffractometry, and differential scanning calorimetry (DSC). Nifedipine (calcium antagonist) and propranolol HCl (beta-blocker), used for the treatment of hypertension, were chosen as lipophilic and hydrophilic drugs. The microparticles were spherical with diameters in the range of 191-351 microm by the o/w-method, and in the range of 302-477 microm by the w/o/w-method. The encapsulation efficiency (EE) was 91% for nifedipine and 37% for propranolol HCl with the o/w-method, and 83% for nifedipine and 57% for propranolol HCl with the w/o/w-method. DSC and X-ray diffraction studies showed that PCL maintained its semi-crystalline structure, while the drugs were either dispersed or dissolved in the polymer. In vitro release studies revealed a controlled release of nifedipine and propranolol HCl from microparticles prepared by the o/w-method; a burst release of propranolol HCl was observed from microparticles prepared by the w/o/w-method. In conclusion, microparticles containing both a hydrophilic and a lipophilic drug were successfully prepared.

Adrenergic beta-Antagonists↗
PubMed2000

Therapeutic evaluation of free and liposome-encapsulated atovaquone in the treatment of murine leishmaniasis.

The use of drug delivery systems may reduce the toxicity and improve the activity of anti-leishmanial compounds. The activity of atovaquone (ATV)-loaded liposomes was compared by determination of median effective doses (ED(25) and ED(50)), with that of free ATV in a murine model of visceral leishmaniasis induced by Leishmania infantum. On day 0, mice were infected intravenously with 4.10(7) promastigotes and treated via the tail vein on days 15, 17 and 19 by free drug in a DMSO/cremophor/water solution (0.2 to 1.6 mg/kg body weight) or by liposomal drug (0.04 to 0.32 mg/kg body weight). Mice were killed and livers and spleens were removed and weighed on day 21 p.i. and liver parasite burdens evaluated using the Stauber method. Effective doses were determined using the Hill representation relating the percentage of parasite suppression to the dose. Liposomal ATV was significantly more effective than the free drug in reducing liver parasites (61.6% of parasite suppression at a dose of 0.32 mg/kg vs 34.9% at a dose of 1.6mg/kg). Liposomal ATV was 23 times more active than the free drug (ED(25) value=0. 02+/-0.01 mg/kg vs 0.46+/-0.15 mg/kg for free drug). It was not possible to obtain the ED(50) for free ATV because the dose-response curve reached a plateau around 33% of parasite suppression. Conversely, the ED(50) for liposomal ATV was 0.17+/-0.05 mg/kg. 100% efficacy of bound ATV could be obtained with a concentration of 1. 77+/-0.35 mg/kg. A significant decrease in spleen weights was also observed reflecting a leishmanicidal activity of ATV. These results suggest that liposome loaded ATV is more efficacious than the free drug against Leishmania infantum in this murine model.

Animals↗
PubMed2000

Measles virus induces functional TRAIL production by human dendritic cells.

Measles virus infection induces a profound immunosuppression that can lead to serious secondary infections. Here we demonstrate that measles virus induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA and protein expression in human monocyte-derived dendritic cells. Moreover, measles virus-infected dendritic cells are shown to be cytotoxic via the TRAIL pathway.

Apoptosis Regulatory Proteins↗
PubMed1999

Pretreatment with a potassium-channel opener before prolonged cardiac storage: an evaluation in an experimental brain death model.

BACKGROUND: Pretreatment with a potassium-channel opener has been shown to improve functional recovery after long-term cardioplegic arrest. We evaluated whether pretreatment with the potassium-channel opener cromakalim is beneficial in a more clinically relevant experimental model of brain death in the rabbit. METHODS: Four groups of rabbits were studied in a 2 x 2 factorial experiment (n = 8 per group). Rabbits were subjected to a sham operation or 90 minutes of brain death induced by inflating a subdurally placed balloon. Thirty minutes before heart explantation, rabbits received either no pretreatment or an intravenous injection of cromakalim, 30 microg/kg. Hearts then received 5 hours' hypothermic storage in St. Thomas' Hospital solution and were assessed on a buffer-perfused isolated heart preparation. Hemodynamic recovery, coronary flow, and creatine kinase release were determined after 60 minutes of reperfusion. RESULTS: Systolic function and diastolic function were significantly altered in hearts explanted from brain-dead rabbits compared with hearts from rabbits having a sham operation. Cromakalim pretreatment had no significant effect on poststorage systolic or diastolic function of hearts explanted from brain-dead or sham-operation rabbits. Further, cromakalim pretreatment did not affect coronary flow or overall creatine kinase release during reperfusion. CONCLUSIONS; In vivo pretreatment of brain-dead rabbits or anesthetized rabbits with an intravenous injection of cromakalim had no significant effect on functional recovery of or enzymatic release from explanted hearts after 5 hours' hypothermic storage and 60 minutes' reperfusion. These findings underscore the importance of clinically relevant experimental models.

Animals↗