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J P Andreux

Publications and source records attributed to J P Andreux.

At least 19 recordsLinked to original sources
PubMed2005

A relevant in vitro rat model for the evaluation of blood-brain barrier translocation of nanoparticles.

Poly(MePEG2000cyanoacrylate-co-hexadecylcyanoacrylate) (PEG-PHDCA) nanoparticles have demonstrated their capacity to reach the rat central nervous system after intravenous injection. For insight into the transport of colloidal systems across the blood-brain barrier (BBB), we developed a relevant in vitro rat BBB model consisting of a coculture of rat brain endothelial cells (RBECs) and rat astrocytes. The RBECs used in our model displayed and retained structural characteristics of brain endothelial cells, such as expression of P-glycoprotein, occludin and ZO-1, and immunofluorescence studies showed the specific localization of occludin and ZO1. The high values of transendothelial electrical resistance and low permeability coefficients of marker molecules demonstrated the functionality of this model. The comparative passage of polyhexadecylcyanoacrylate and PEG-PHDCA nanoparticles through this model was investigated, showing a higher passage of PEGylated nanoparticles, presumably by endocytosis. This result was confirmed by confocal microscopy. Thanks to a good in vitro/in vivo correlation, this rat BBB model will help in understanding the mechanisms of nanoparticle translocation and in designing new types of colloidal carriers as brain delivery systems.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

PEGylated polycyanoacrylate nanoparticles as vector for drug delivery in prion diseases.

PEGylated polymeric nanoparticles are hereby presented as a potential efficient drug carrier for the delivery of active therapeutic molecules in prion experimental diseases. Based on their blood long-circulating characteristics, these PEGylated particles made by the amphiphilic copolymer poly [methoxy poly(ethylene glycol) cyanoacrylate-co-hexadecyl cyanoacrylate] (PEG-PHDCA), showed comparatively conventional non-PEGylated nanoparticles, a higher uptake by the spleen and the brain which are both the target tissues of PrPres accumulation in scrapie infected animals.

Animals↗
PubMed2001

Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery.

PURPOSE: The aim of this study was to evaluate the ability of long-circulating PEGylated cyanoacrylate nanoparticles to diffuse into the brain tissue. METHODS: Biodistribution profiles and brain concentrations of [14C]-radiolabeled PEG-PHDCA, polysorbate 80 or poloxamine 908-coated PHDCA nanoparticles, and uncoated PHDCA nanoparticles were determined by radioactivity counting after intravenous administration in mice and rats. In addition, the integrity of the blood-brain barrier (BBB) after nanoparticles administration was evaluated by in vivo quantification of the diffusion of [14C]-sucrose into the brain. The location of fluorescent nanoparticles in the brain was also investigated by epi-fluorescent microscopy. RESULTS: Based on their long-circulating characteristics, PEGylated PHDCA nanoparticles penetrated into the brain to a larger extent than all the other tested formulations. Particles were localized in the ependymal cells of the choroid plexuses, in the epithelial cells of pia mater and ventricles, and to a lower extent in the capillary endothelial cells of BBB. These phenomena occurred without any modification of BBB permeability whereas polysorbate 80-coated nanoparticles owed, in part, their efficacy to BBB permeabilization induced by the surfactant. Poloxamine 908-coated nanoparticles failed to increase brain concentration probably because of their inability to interact with cells. CONCLUSIONS: This study proposes PEGylated poly (cyanoacrylate) nanoparticles as a new brain delivery system and highlights two requirements to design adequate delivery systems for such a purpose: a) long-circulating properties of the carrier, and b) appropriate surface characteristics to allow interactions with BBB endothelial cells.

Acrylic Resins↗
PubMed2000

Role of spleen macrophages in the clearance of scrapie agent early in pathogenesis.

The involvement of spleen macrophages in the early stages of scrapie pathogenesis was studied by applying the 'macrophage-suicide technique' to scrapie-infected mice. This method comprises critically the intravenous administration to mice of dichloromethylene disphosphonate encapsulated into liposomes. Depletion of spleen macrophages before scrapie infection induced an increased amount of scrapie inoculum in the spleen, consequently leading to accelerated scrapie agent replication in the early phase of pathogenesis, as followed by PrPres accumulation, a specific hallmark of scrapie. The same effect was observed when spleen macrophages were depleted just before the beginning of scrapie agent replication. These findings suggest that macrophages may partly control scrapie infection in peripheral tissues by sequestration of the scrapie inoculum and may thus impair early scrapie agent replication in the spleen. In addition to macrophages, most follicular dendritic cells and B lymphocytes, which are thought to support scrapie agent replication, were also transiently depleted by dichloromethylene disphosphonate administration. This suggests that a compensatory mechanism is sufficient to ensure the persistence of infection in these early stages of pathogenesis.

Analgesics, Non-Narcotic↗
PubMed2000

Elderly patients treated with tinzaparin (Innohep) administered once daily (175 anti-Xa IU/kg): anti-Xa and anti-IIa activities over 10 days.

Since low molecular weight heparins (LMWH) are partly eliminated by renal excretion, their pharmacodynamic profile may be modified in very elderly patients with age-related renal impairment. The aim of this prospective study was to determine whether tinzaparin (Innohep) 175 anti-Xa IU/kg administered subcutaneously once daily over 10 days does accumulate in hospital patients greater than 70 years of age. Plasma anti-Xa and anti-IIa amidolytic levels and APTT were determined prior to the first injection (day 0), and then, at peak level i.e. 5 h after the second injection (day 2) and subsequently on days 5, 7 and 10. Thirty consecutive inpatients (6 men, 24 women) requiring LMWHs at a curative dose for acute thromboembolic disease were included. Patients' characteristics (mean +/- SD) were: age 87.0+/-5.9 years (range 71-96), body weight 62.7+/-14.6 kg (range 38-90) and creatinine clearance 40.6+/-15.3 mL/min (range 20-72). The mean actual dose of tinzaparin delivered was 174.8 anti-Xa IU/kg. Since no patient had an anti-Xa activity above 1.5 IU/mL, the dose of tinzaparin remained fixed over 10 days. Anti-Xa and anti-IIa peak levels measured on day 2 were 0.66+/-0.20 IU/mL (range 0.26-1.04) and 0.33+/-0.10 IU/mL (range 0.18-0.55), respectively. Ex vivo anti-Xa/anti-IIa ratios were close to 2.1. APTT ratios (patient/control) were strongly correlated with anti-IIa activity (p <0.01). There was no progressive increase of the anti-Xa and anti-IIa activities after repeated administration of tinzaparin over the 10 day treatment period. No correlation was found between anti-Xa and anti-IIa activities and age, weight, or creatinine clearance. No major bleeding occurred during the study and only one minor haematoma at the injection site was reported. No thrombo-embolic complication or death occurred. Tinzaparin may thus be administered safely at a treatment dose (175 anti-Xa IU/kg) in older patients with age-related renal impairment. Neither dose adjustment, nor serial anti-Xa activity monitoring seems to be required in patients with creatinine clearance above 20 mL/min during the first ten day treatment.

Age Factors↗
PubMed1999

[Myelodysplastic syndromes. Diagnosis and care in patients over 70 years of age].

A FREQUENT CONDITION IN GERIATRICS: Myelodysplastic syndromes comprise a group of bone marrow disorders characterized by abnormal hematopoetic stem cell clones. They are generally observed after 60 years of age with a peak frequency in the 70-80 year age group. Prevalence is probably underestimated and diagnosis is commonly made in geriatric wards. DIAGNOSIS: Clinical presentations vary widely, making diagnosis a difficult task. Cytology studies play a predominant role. Recent progress in our understanding of myelodysplastic syndromes have been achieved with cytogenic and molecular biology techniques, although the diagnostic procedures and management of elderly subjects have changed little. DISEASE COURSE AND TREATMENT: Prognosis of myleodysplastic syndromes is highly variable and mainly depends on the type of syndrome according to the international FAB classification. Therapeutic management in patients over 70 is limited in most cases to symptomatic treatment, principally with transfusional support.

Age Factors↗
PubMed1999

In vitro evaluation of nanoparticles spleen capture.

After intravenous injection, the main part of nanoparticles trapped by the spleen are concentrated in the marginal zone. The first step of this capture is the adhesion of the particles to the marginal zone macrophages. As classical techniques of cell suspension preparation did not allow to isolate without damage these actively capturing cells, tightly bound to a well-developed reticular meshwork, we designed a tissue slice incubation method, in order to study in vitro the interaction of nanoparticles with these particular macrophages, in conditions close to in vivo. In a serum supplemented medium, this in vitro model was able to give similar uptake profile than after intravenous injection of nanoparticles thus proving its validity. Surprisingly, no significant decrease of nanoparticles capture was observed when the medium was depleted from complement, immunoglobulins or proteins affine for heparin, while substitution of serum by purified albumin allowed a near optimal uptake. Addition of competitive ligands for lectin-like receptors did not show any clear inhibition of spleen capture. On the other hand, the scavenger receptor blocking agents, such as maleylated albumin or polyinosinic acid, induced a strong reduction of the spleen nanoparticles uptake. Thus, this paper proposes an in vitro binding assay as a reliable method to investigate the spleen capture of a large variety of nanoparticulate drug carriers. It is also a useful methodology to highlight the interactions between spleen cells and nanoparticles. The data obtained suggest that capture of nanoparticles depends on a multifactorial and complex phenomenon involving for a part albumin and the scavenger receptor.

Animals↗
PubMed1999

Spleen capture of nanoparticles: influence of animal species and surface characteristics.

PURPOSE: To investigate the influence of animal species and nanoparticle surface characteristics on the intrasplenic distribution of polystyrene nanoparticles. METHODS: Two types of fluorescent polystyrene nanoparticles (Estapor and Fluoresbrite), plain or coated, were used in mice and rats. First, a fluorimetric method was developed for nanoparticle tissue quantification. Then, intrasplenic distribution of plain or coated nanoparticles was studied using histological examination and image analysis. Finally, the role of direct interactions between nanoparticles and spleen capturing cells was assessed by in vitro binding assays, using incubation of thick spleen slices with polystyrene nanoparticles. RESULTS: The two types of polystyrene nanoparticles showed different levels of trapping: Fluoresbrite nanoparticles were more efficiently trapped by the spleen than Estapor nanoparticles, both in mice and rats. In mice, most of the injected nanoparticles were localized in the marginal zone of the spleen, involving a special population of capturing cells, while in rats, the predominant capture occured in the red pulp. In mice, coated nanoparticles were localized both in the marginal zone and in the red pulp, whereas the coating did not seem to change the intrasplenic distribution of the nanoparticles in rats. CONCLUSIONS: These complementary approaches showed different uptake pathways of nanoparticles, according to their surface characteristics and the rodent species used.

Animals↗
PubMed1999

Ruling out acute deep vein thrombosis by ELISA plasma D-dimer assay versus ultrasound in inpatients more than 70 years old.

In geriatric care, deep-vein thrombosis (DVT) is mostly diagnosed by noninvasive techniques. The objectives of this prospective study were: (1) to evaluate the power of ELISA plasma D-dimer assay versus ultrasound (US) in ruling out acute DVT of the lower limbs in symptomatic geriatric inpatients, and (2) to determine the most effective D-dimer cutoff value over the age of 70 years. Over a 10-month period, inpatients with suspected lower limb DVT simultaneously underwent US examination and ELISA plasma D-dimer assay. Noninclusion criteria were comorbid conditions able to modify the D-dimer level. Data were processed by receiver operating characteristic (ROC) curve analysis. In total, 150 patients (125 women, 25 men), average age 86.3 years (range 70-101) were included. A diagnosis of lower limb DVT was established in 53 patients (35.3%). With a 500 ng/mL D-dimer cutoff conventional value, DVT was ruled out in only five patients (3.3%), whereas a 750 ng/mL value ruled out DVT in 19 patients (12.7%) with a sensitivity of 98.1%, and a negative predictive value of 95.0%. The only false negative corresponded to a patient with a 15-mm thrombus in the distal calf. In inpatients above 70, an ELISA plasma D-dimer value smaller than 750 ng/mL is a rapid reliable noninvasive means to rule out lower limb DVT, if color flow Doppler ultrasound is not available on site.

Aged↗
PubMed1999

[Targeting bone marrow with the help of polyalkylcyanoacrylate nanoparticles].

Using a mouse model, we examine drug targeting towards bone marrow. One cytotoxic (doxorubicin) and one stimulating (rhG-CSF), bound to polyalkylcyanoacrylate nanoparticles, were studied. Histological studies, using a fluorescence microscope, showed rapid capture of nanoparticles by bone marrow macrophages and granulocytes as soon as 15 minutes after injection into the blood stream. Doxorubicin nanoparticles, administered at a dose of 11 mg/kg were more toxic than free doxorubicin on all blood and marrow cell lines. Moreover, the choice of the nature of the polymer had an influence on toxicity: doxorubicin polyisohexylcyanoacrylate nanoparticles were more toxic than polyisobutylcyanoacrylate particles. Quantification of doxorubicin in bone marrow has confirmed these results. The bone marrow concentrations observed demonstrated that there was a high level of targeting towards the bone marrow that would be very interesting to use for a stimulating drug. Nevertheless, rhG-CSF nanoparticles did not show better efficacy than free rhG-CSF.

Animals↗
PubMed1998

Polyalkylcyanoacrylate nanoparticles as carriers for granulocyte-colony stimulating factor (G-CSF).

The human recombinant granulocyte colony-stimulating factor (rhG-CSF) is largely used in the treatment of neutropenia occurring during chemotherapy. After injection, this glycoprotein distributes through the whole body. Thus, to obtain high and durable bone marrow concentrations, targeting with polyalkylcyanoacrylate nanoparticles was considered. Two methods of preparation were investigated: anionic polymerization and precipitation of the preformed polymer. By anionic polymerization, it was possible to associate more than 66% of rhG-CSF with nanoparticles (polyisobutyl- or polyisohexylcyanoacrylate nanoparticles) when the glycoprotein was added at the end of the polymerization process. It has been shown that the rhG-CSF was mainly adsorbed on the surface of the nanoparticles and most of the colony stimulating activity was conserved. Using precipitation of performed polyisohexylcyanoacrylate, 90% of rhG-CSF was associated with nanoparticles, the protein being mainly adsorbed onto the nanoparticle surface. In this case, a decrease of the colony stimulating activity was however observed. Whatever the method used, the in vitro release of rhG-CSF from the polyisohexylcyanoacrylate nanoparticles, was progressive during 8 h in seric conditions. Nevertheless, using mice as an animal model, it has been shown that the short-term effects of intravenously injected rhG-CSF were not increased by its association with polyisohexylcyanoacrylate nanoparticles.

Animals↗
PubMed1997

Splenic trapping of nanoparticles: complementary approaches for in situ studies.

PURPOSE: To identify more accurately in the spleen, the areas and the cells where nanoparticulate carriers were taken up from the blood flow, a series of complementary approaches were used. METHODS: First, in and ex vivo examination of the whole spleen led to a global view of all the trapping areas. Then, histological studies on frozen sections of the same organ allowed for a more precise localization of these areas and image analysis gave an evaluation of tissue distribution of the nanoparticles. Finally, immunological and enzymological characteristics of the capturing cells were determined in situ, using monoclonal antibodies (F4/80 and anti-sialoadhesin) and cytochemical reactions (esterases and acid phosphatase). Furthermore incubation of spleen slices with different nanoparticles was used so as to know if the capture was due to a high capturing capacity of these cells or to a high blood flow in their vicinity. RESULTS: It was shown that more than 90% of the splenic capture was localized in the marginal zone of the follicles. The capturing cells form a special population of macrophages inserted in a reticular meshwork, showing low esterase and acid phosphatase activities, giving faint or no reaction with F4/80 or anti-sialoadhesin antibodies. The circulating nanoparticles were quickly trapped with rather low specificity by these cells. CONCLUSIONS: Combination of coherent approaches allowed for the tracking of capturing cells from in vivo observations to their in situ identification on immunological and enzymological criteria.

Animals↗
PubMed1997

Factors involved in the anaemia of chronic disorders in elderly patients.

Erythropoietin secretion was evaluated in the anaemia of chronic disorders in elderly patients, since it has been shown that this secretion is impaired in adults. We looked for a possible role of inflammatory cytokines: tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) on erythropoietin production. The influence of nutritional status on the anaemia was also investigated. Erythropoietin secretion was significantly increased in elderly patients with anaemia of chronic disorders (ACD) and inversely correlated with haemoglobin concentrations in infectious and inflammatory diseases. Plasma TNF alpha levels were significantly enhanced only in cancerous patients, but no correlation could be established between TNF alpha and erythropoietin or haemoglobin. No noticeable increase of IL-1 beta levels was observed in ACD. These findings suggest that systemic TNF alpha or IL-1 beta are not involved in the erythropoietin response to ACD. Albumin levels were decreased in anaemic patients. Further investigations of the effects of a nutritional supplementation in elderly patients with ACD may be of interest.

Aged↗
PubMed1996

Comparative study of human red blood cell analysis with three different field-flow fractionation systems.

An extensive multi-laboratory study was conducted to compare three different field-flow fractionation (FFF) systems for use in the analysis of human erythrocytes. The object of this study was to determine the relationship between the FFF elution properties for each system and the traditional hematological blood cell parameters. One centrifugal system (Utah) and two gravitational systems (Paris and Abbott) were compared. In order to analyze erythrocyte populations with a broad range of hematological indices, blood samples were collected from individuals heterozygous for sickle cell anemia (A/S) and also from normal controls (A/A), and these were analyzed at each site. Identical samples were analyzed by the Abbott and Utah sites. With all three systems, blood samples from each category produced narrow, overlapping distributions of FFF retention ratios, with the Abbott and Utah systems showing slight elevations in the mean retention ratios for the sickle cell samples. Blood cell elution peak characteristics were compared with standard hematological parameters for each of the FFF systems, and negative correlations were consistently found between mean corpuscular volume (MCV) and retention ratios. Positive correlations were found between red cell distribution width (RDW) and retention ratios. Elevated FFF retention ratios were frequently found with blood samples having abnormal hematological profiles. These results demonstrate that the three differently configured systems all produce similar analysis profiles for erythrocytes from the classes studied here. The relationships between FFF parameters and hematological indices were consistent for all systems.

Anemia, Sickle Cell↗
PubMed1996

Cells involved in the capture of nanoparticles in hematopoietic organs.

The affinity of nanoparticles for hematopoietic organs could be valuable for the targeting of certain stimulating factors to those tissues, but this affinity should also be taken into account in the toxicological evaluation of those carriers, especially when they are loaded with antimitotic compounds such as doxorubicin. However, the cells responsible for the capture of the nanoparticles and their localization in these organs is an important point to know before trying to modulate the nanoparticle's tissue distribution. Thus, we have studied, in this paper, the capture, the localization, and the retention in the bone marrow and in the spleen of biodegradable poly(isohexyl cyanoacrylate) nanoparticles as well as of nonbiodegradable polystyrene nanoparticles. The histological localization of these nanoparticles has been completed by cytological localization with a method used in cytochemistry for the evaluation of intracellular accumulation of various substances, such as iron deposits in bone marrow sideroblasts. These data indicate that, in the bone marrow, after a quick passage through the endothelium, nanoparticles were dispersed throughout in the tissue and captured by all types of phagocytizing cells. In the spleen, nanoparticles were mainly localized in large angular capturing cells in the marginal zone of the lymphoid follicles.

Animals↗
PubMed1996

Blood smears and prenatal diagnosis.

Fetal blood sampling is a widely used technique for both diagnostic and therapeutic purposes. However, despite the fact that examination of blood smears is a critical step in the study of a large variety of disorders, the place of fetal blood smears analysis has been overshadowed by more sophisticated diagnostic tools such as those offered by molecular biology. Nevertheless, as highlighted by four cases presented in this paper, the role of fetal blood smears examination must be re-emphasized. The recognition of abnormal cytological findings limits the number of possible aetiologies, thus elegantly contributing to the diagnosis without multiplying unnecessary test techniques.

Fetal Blood↗