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Biomedical subjects

F Puisieux

Publications and source records attributed to F Puisieux.

At least 55 records · Page 3Linked to original sources

[Clinical symptomatology and prognosis of periarteritis nodosa in the elderly. Retrospective study of 25 periarteritis nodosa cases in young adults and 22 cases in aged patients].

Between 1985 and 1995, 47 patients with evidence of polyarteritis nodosa were seen at the department of Internal Medicine. Thirty-nine patients fulfilled histological and/or arteriographic diagnostic criteria, and in eight patients, the diagnosis was based on clinical criteria. At the onset of the disease, 25 patients were below the age of 65 (group A) and 22 were above the age of 65 (group B). Except for increased frequency of weight loss in group B and increased frequency of cutaneous signs (purpura and nodes) in group A, no significant differences were found in clinical and biological features. The mean duration of follow-up was 46.9 +/- 36.5 months. The number of deaths was significantly higher among the elderly (ten deaths in group B versus two in group A).

Adult↗

Formulation of a charcoal suspension for intratumor injection. Part 1: Study of the nature, granulometry, and concentration.

PURPOSE: We developed a charcoal suspension formulation to be injected intratumorally so that human breast cancers can be tatooed prior to chemotherapy. This deposit is intended to guide the surgeon at the time of the biopsy and resection, especially when the tumor nodule is not visible. The stain should remain in the tumor as long as the patient is on chemotherapy and should be harmless. METHODS: We studied on the effect on the nature of the charcoal, its granulometric profile, and its concentration. We then measured diffusion in vitro, in gel, and in vivo in experimental tumors. RESULTS: The formulation selected was prepared with a peal charcoal suspension in water for parenteral injections, with 50% of the particles measuring on average between 2 and 5 microns. The finest particles (< 2 microns) seem to produce the greatest in vitro diffusion and are more readily phagocyted by macrophages and thus eliminated from the tumor by those cells. CONCLUSIONS: This charcoal suspension has satisfactory formulation characteristics and diffuses the least, be it in vitro or in vivo, mainly due to the granulometric distribution of the suspension.

Animals↗

Reversion of multidrug resistance with polyalkylcyanoacrylate nanoparticles: towards a mechanism of action.

Polyalkylcyanoacrylate (PACA) nanoparticles loaded with doxorubicin allowed multidrug resistance to be overcome in vitro. However, increased cytotoxicity is not always correlated with an increased level of intracellular drug. Although we have previously shown that PACA nanoparticles are not endocytosed by tumour cells, we report here that a direct interaction between nanoparticles and cells is a necessary requirement for overcoming resistance. In addition, the results showed that the degradation products of PACA (mainly polycyanoacrylic acid) in the presence of doxorubicin are able to increase both accumulation and cytotoxicity, thus suggesting the formation of a doxorubicin-polycyanoacrylic acid ion pair. It is therefore concluded that resistance is overcome as a result of both the adsorption of nanoparticles to the cell surface and increased doxorubicin diffusion by the accumulation of an ion pair at the plasma membrane.

Animals↗

Liposomes bearing platelet proteins: a model for surface functions studies.

An improved procedure for the direct transfer of membrane proteins from human platelets to liposomes involving the treatment of platelets with linolenic acid was developed. The transfer of platelet proteins to liposomes prepared from the mixture of L-alpha-dimyristoyl-phosphatidylcholine/sphingomyelin in the molar ratio 80/20 appeared to be significantly enhanced compared with liposomes prepared from the same components mixed in other ratios. A wide range of platelet proteins was transferred, the most important being GPIb (170 kDa), GPIIb/IIIa (135 and 110 kDa). GPIV (90 kDa), GPIX (24 kDa) and the serotonin transporter (68 kDa). The recognition interactions between these proteoliposomes and specific protein antibodies clearly indicate that the non-invasive procedure used in this study ensured the reproducible transfer of platelet proteins without essentially altering their original conformation. The obtained results reveal also that the affinity of proteoliposomes to bind paroxetin was virtually the same as that of the native serotonin transporter. These results provide an indication of the possible use of such proteoliposomes as models to study at the molecular level the interaction of these proteins with their ligands.

Blood Platelets↗

Effect of PEO surface density on long-circulating PLA-PEO nanoparticles which are very low complement activators.

The rapid uptake of injected nanoparticles by cells of the mononuclear phagocytes system (MPS) is a major obstacle when a long blood circulation time is needed. Whereas nanoparticles made from PLA and stabilized by surfactants (PLA-F68) are rapidly phagocytized, the rate of phagocytosis is strongly reduced in case of nanoparticles made from a diblock copolymer (PLA-PEO). Because of the role of the complement system in opsonization, this difference of phagocytosis was hypothesized to be related to this system. An important complement consumption was obtained in 5 min in the presence of PLA-F68 particles. In the presence of a higher surface area of PLA-PEO particles possessing a high PEO surface density, the consumption remained very low. When the average PEO surface density was decreased on such particles below a given threshold, a fast and strong complement consumption occurred again. These experimental data support the concept of steric repulsion towards proteins, by surfaces covered with terminally attached PEO chains and emphasize the prime importance of PEO surface density in such an effect. The major, but probably not exclusive, role of complement as an opsonin capable of inducing a fast phagocytosis by MPS should be taken into account concerning the in vitro evaluation of nanoparticles as candidates for a long blood circulation.

Biocompatible Materials↗

Prevalence and clinical significance of antiphospholipid antibodies in heart valve disease: a case-control study.

The purposes of this study were (1) to assess the prevalence of antiphospholipid (aPL) antibodies in patients with non-specific heart valve disease referred for valve replacement and (2) to determine whether the presence of aPL antibodies carries a risk for thrombotic events during a postoperative follow-up in a prospective cohort. The sera of 89 consecutive patients and 80 matched control subjects were tested for antibodies to cardiolipin (immunoglobulin G and immunoglobulin M) and for lupus anticoagulant. The prevalence of aPL antibodies was significantly higher in patients (19 [21%] of 89) than in control subjects (7 [9%] of 80) (p < 0.05). Patients were divided into two subgroups according to the presence (subgroup A) or the absence (subgroup B) of aPL antibodies. No significant difference in age or sex ratio was observed between the two subgroups. A history of arterial thrombosis was more frequent in subgroup A (8 [42%] of 19) than in subgroup B (8 [11%] of 70) (p < 0.01). No significant difference with respect to the occurrence of thrombotic events was observed during a median follow-up period of 8.7 months. Thus a high prevalence of aPL antibodies was found in patients referred for heart valve replacement compared with matched control subjects. No increased risk has been demonstrated in the patients with aPL antibodies.

Antibodies, Anticardiolipin↗

In-vitro and in-vivo evaluation of a new amphotericin B emulsion-based delivery system.

The in-vitro and in-vivo toxicity and activity of a new emulsion-based delivery system for amphotericin B (AmB-E) and of deoxycholate-amphotericin B (Fungizone) were studied. In vitro, Candida albicans and human red blood cells (RBCs) were treated with either product and dose-response curves for various cellular effects (changes in potassium cell content, haemoglobin leakage from RBCs and colony-forming ability of fungal cells) were obtained. AmB-E was less toxic than Fungizone against human RBCs and equally active against C. albicans cells. In-vivo studies showed that the LD50 of AmB-E and Fungizone in noninfected OF1 mice were 7.24 and 3.46 mg/kg, respectively. The therapeutic efficacy of AmB-E was assessed in murine candidiasis. Firstly, the efficacy of equal doses (0.8 mg/kg) of AmB-E and Fungizone was evaluated in infected mice. Both formulations increased the survival time compared to the control and were equally effective in reducing the cfu counts in the kidney. In the same model of infection, the maximum tolerated doses (MTD) of Fungizone and AmB-E were determined in order to study the efficacies of Fungizone and AmB-E at their respective MTD. AmB-E significantly increased the number of long-term survivors compared with Fungizone (MTD:2 and 1 mg/kg, respectively). Thus, AmB-E was more effective than Fungizone for treatment of systemic mycoses at the MTD.

Amphotericin B↗

[Sneddon syndrome and mitral valve disease].

The authors report the case of a 37-year-old woman with widespread livedo and transient cerebral ischaemia (Sneddon's syndrome). The patient had also mitral valve disease who required commissurotomy two years ago. The research of anticardiolipin antibodies was negative. The relations between Sneddon's syndrome, antiphospholipid antibodies and valve lesions are discussed.

Adult↗

[Congestive heart failure in the elderly. Value of Doppler echocardiography].

Fifty-eight consecutive elderly patients (seven men and 51 women, mean age 84 +/- 6) admitted for congestive heart failure were prospectively investigated by doppler echocardiography in order to 1) define the prevalence of cardiac failure with normal left ventricular systolic function, 2) estimate the role of abnormalities of left ventricular filling (diastolic dysfunction), 3) evaluate echodoppler parameters for assessment of diastolic function: ratio of early peak on atrial peak of filling velocities (E/A), mitral deceleration time (MDT) and isovolumic relaxation time (IRT). Of the 58 patients, 32 (55%) had normal left ventricular systolic function and 26 (45%) had systolic dysfunction. Of the 32 patients with normal systolic function, diastolic function could not be evaluated in nine patients, was abnormal in 16 and normal in seven. Congestive heart failure with normal systolic function is very frequent in the elderly subject. Sensitivity of clinical data being too low, doppler echocardiography is the easiest noninvasive technique for defining abnormalities of both left ventricular systolic and diastolic function. In the elderly, MDT and IRT are more sensitive parameters than E/A for the diagnosis of diastolic dysfunction.

Aged↗

Mechanisms involved in iontophoretic transport of angiotensin.

PURPOSE: The feasibility of using iontophoresis to enhance the permeation rate of a model peptide was investigated in vitro using hairless mouse skin. METHODS: Angiotensin 2 (AT 2) was employed as a permeant probe, using optimum iontophoresis conditions. A number of physicochemical parameters (donor ionic strength; valence of competitive ions; pH of donor solution) were studied with the aim of exploring the mechanisms involved in the iontophoretic transport through the skin: electrokinetic transport or convective transport. For this purpose, the magnitude of the convective solvent flow was also evaluated by the permeation of (3H) H2O. The interest of pulsed currents for peptide delivery was also investigated and the effect of current density and frequency was studied. RESULTS: AT 2 transport was found to be enhanced 20-fold in comparison to passive permeation and was found to be proportional to the current density with direct currents as with pulsed currents. CONCLUSIONS: Although the flux enhancement of ions during iontophoresis is due principally to the electrical potential gradient, secondary effects such as convective solvent flow contribute also to flux enhancement of peptide delivery. This effect is dependent of physicochemical conditions of formulation.

Angiotensin II↗

Stimulation of movement and acrosome reaction of human spermatozoa by PC12 liposomes encapsulating ATP.

The effect of co-incubating human spermatozoa with 8 mmol/L dilauroylphosphatidylcholine (PC12) liposomes containing 6 mmol/L adenosine 5'-triphosphate (LATP) was assessed by CASA and compared to that obtained with blank PC12 liposomes (LB). The aim of this study was to investigate if such treatments can improve sperm movement and sustain sperm motility over time. Significant and similar increases in straight-line velocity and linearity of sperm movement in B2 capacitating medium (both p < 0.01) were obtained with LB and LATP treatments (final concentration: 0.38 mmol/L PC12 and 0.5 mmol/L ATP) while in Tyrode's medium supplemented with 10 mg/mL BSA, these movement parameters were increased significantly only in sperm aliquots treated with LATP. Furthermore, after incubation for 0.5 h in Tyrode's, a bioluminescence assay of intracellular ATP indicated no significant change in ATP concentration for LATP-treated spermatozoa while the ATP content of control and LB-treated spermatozoa decreased significantly during the same period (both p < 0.05). The effect of liposomes on the acrosome reaction was also investigated jointly with CASA. These experiments were performed by fluorescence microscopy, using PSA-FITC and the supravital stain Hoechst 33258. After a precapacitation period of 3 h in BWW medium the spermatozoa were incubated for 1 h with LATP, LB, LB+free ATP and free ATP alone (final concentration 0.5 mmol/L ATP). Under these conditions the percentage of acrosome-reacted spermatozoa was increased similarly after LATP and LB treatments compared to control (respectively from 4.9 to 12%, p < 0.01 and 4.9 to 11.3%, p < 0.05) but the percentage of true acrosome-reacted spermatozoa, and the values for all movement characteristics (except percentage motility) were increased significantly only with LATP treatment. The results indicate the potential of PC12 vesicles for introducing highly hydrophilic compounds into spermatozoa, as well as for modulating membrane structures and functions required for fertilization.

Acrosome↗

Preparation and characterization of dipalmitoylphosphatidylcholine liposomes containing interleukin-2.

Human recombinant interleukin-2 (IL-2) has been associated or mixed with small unilamellar vesicles prepared from dipalmitoylphosphatidylcholine (DPPC). Whatever the mode of IL-2 introduction, a considerable proportion of the added protein was associated with the liposomes, as determined by gel filtration and ultrafiltration/centrifugation, suggesting that IL-2 can interact with the lipid bilayer as well as being entrapped within the aqueous phase. Moreover, IL-2 prevented the aggregation/fusion of the vesicles at 4 degrees C. Liposome-associated protein was partially protected from digestion by pepsin, especially at the C-terminal, since no fluorescence emission from the tryptophan in this region was detected in the resulting peptides after separation by HPLC. Such systems could constitute a sustained release form of IL-2 for immunotherapy.

1,2-Dipalmitoylphosphatidylcholine↗

Factors influencing macrophage activation by muramyl peptides: inhibition of NO synthase activity by high levels of NO.

Treatment with muramyldipeptide (MDP) or a lipophilic derivative (MTP-Chol) included in nanocapsules renders macrophages cytostatic towards tumor cells. At the same time, nitric oxide (NO) synthase (EC 1.14.23) activity is induced, as determined by measurement of the two end products of the reaction (nitrite and L-citrulline). The objective of this study was to investigate some factors which might influence this activation and explain the decreased response observed at high nanocapsule concentrations. The glucose content of the medium did not seem to be limiting. Addition of indomethacin decreased nitrite production in the effector phase, suggesting a role for prostaglandins in the maintenance of the activated state. We also tested the hypothesis that NO itself might regulate inducible nitric oxide synthase activity. The addition of NO donors (SIN-1 and nitrosoglutathione) or superoxide dismutase to cultures of activated macrophages inhibited the NO synthase activity. Since these NO donors were non toxic towards macrophages, these observations indicate clearly that the addition of exogenous NO to that formed by the enzymatic reaction can cause inhibition of the inducible NO synthase.

Acetylmuramyl-Alanyl-Isoglutamine↗

High-performance liquid chromatographic assay for the simultaneous determination of ethyl clofibrate and clofibric acid in plasma. Evaluation of plasma stability of ethyl clofibrate polylactic nanocapsules in human and rat plasmas.

A rapid, sensitive, and selective HPLC assay was developed for the simultaneous determination of ethyl clofibrate and its major metabolite, clofibric acid, in plasma of humans and rats. The assay involves extraction of the compounds into chloroform-isoamyl alcohol (99:1, v/v) from plasma acidified with sulfuric acid. For human plasma, the overall recoveries of ethyl clofibrate and clofibric acid were 63 and 90%, respectively. The limits of detection of the assay for ethyl clofibrate and clofibric acid in human plasma were 1.1 and 1.5 micrograms/ml, respectively. Limits of quantitation of the assay for ethyl clofibrate and clofibric acid in human plasma were 3.6 and 4.9 micrograms/ml, respectively. The HPLC assay was used to monitor the plasma concentration-time profiles of ethyl clofibrate released from polylactic nanocapsules both in man and rat. The simultaneous determination of ethyl clofibrate and clofibric acid provided evidence that these colloidal systems are stable in human plasma whereas they are lysed in rat plasma.

Animals↗

Uptake of doxorubicin from loaded nanoparticles in multidrug-resistant leukemic murine cells.

Previous studies have clearly demonstrated that polyisobutylcyanoacrylate (PIBCA) doxorubicin-loaded nanoparticles (NS-Dox PIBCA) can overcome the resistance of P388/ADR cells. In the present paper, we found that overcoming multidrug resistance with the aid of doxorubicin (Dox) loaded onto these nanoparticles was associated with an increased intracellular drug content. Indeed, after a 6-h incubation period, the amount of cell-associated drug was 5 times higher when the cells were incubated with NS-Dox PIBCA as compared with free Dox. Further experiments, such as uptake studies in the presence of cytochalasin B or efflux studies, indicated a possible mechanism of nanoparticle/cell interaction. These results suggested that nanoparticles did not enter the cells by an endocytic process, in contrast to a previous hypothesis.

Animals↗

[Silicosis and primary Gougerot-Sjögren syndrome].

We report three cases of primary Sjögren's syndrome in silicotic coal miners. All patients fulfilled the diagnostic criteria for Sjögren's syndrome recently established by the European Community study group. One patient had cryoglobulinemia and polynevritis. Another had Raynaud's phenomenon, arthralgia, purpura and polynevritis. Capillary microscopy was normal in all the three patients. Antinuclear antibodies were detected only in one patient, who had also anti-SSa and anti-SSb antibodies. The prevalence of systemic sclerosis, rheumatoid arthritis and probably systemic lupus erythematosus is significantly higher after longstanding occupational exposure to silica. On the contrary, any case of Sjögren's syndrome was till now described in the course of pulmonary silicosis. The physiopathological mechanisms of these associations are misunderstood.

Aged↗

Synthesis and in vitro study of a diglyceride prodrug of a peptide.

A diglyceride derivative of a pentapeptide renin inhibitor, the 1,3-dipalmitoyl-[Iva-Phe-Nle-Sta-Ala-Sta-acetyl]-glycerol was synthesized and tested in vitro as a potential prodrug for oral administration. The ability of the diglyceride analog to inhibit the renin activity was equivalent to that of the parent peptide after predigestion with pancreatic lipase. Furthermore, the presence of the palmitoyl groups was found to induce, in vitro, an efficient protection of the peptide from gastric and intestinal hydrolysis. During incubation with intestinal and gastric fluids, and with alpha-chymotrypsin and pancreatic lipase, the glycerolipidic derivative was more stable than the peptide alone. These results support the use of glycerolipidic prodrug for oral administration of peptides.

Amino Acid Sequence↗