TRAIL-NP hybrids for cancer therapy: a review.

Cancer is a worldwide health problem. It is now considered as a leading cause of morbidity and mortality in developed countries. In the last few decades, considerable progress has been made in anti-cancer therapies, allowing the cure of patients suffering from this disease, or at least helping to prolong their lives. Several cancers, such as those of the lung and pancreas, are still devastating in the absence of therapeutic options. In the early 90s, TRAIL (Tumor Necrosis Factor-related apoptosis-inducing ligand), a cytokine belonging to the TNF superfamily, attracted major interest in oncology owing to its selective anti-tumor properties. Clinical trials using soluble TRAIL or antibodies targeting the two main agonist receptors (TRAIL-R1 and TRAIL-R2) have, however, failed to demonstrate their efficacy in the clinic. TRAIL is expressed on the surface of natural killer or CD8+ T activated cells and contributes to tumor surveillance. Nanoparticles functionalized with TRAIL mimic membrane-TRAIL and exhibit stronger antitumoral properties than soluble TRAIL or TRAIL receptor agonist antibodies. This review provides an update on the association and the use of nanoparticles associated with TRAIL for cancer therapy.

[Primary infection with cytomegalovirus: An infectious cause of splenic infarction]. / Primo-infection à cytomégalovirus : une cause infectieuse d'infarctus splénique.

INTRODUCTION: Cytomegalovirus-associated thrombosis has been extensively reported in the medical literature, mainly in immune-compromised patients. However, the association with splenic infarcts has rarely been reported. CASE REPORT: We report a 32-year-old Caucasian and immunocompetent woman who presented with a splenic infarction during a primary infection with CMV. The differential diagnostic ruled out embolic, hematologic, gastrointestinal and coagulation disorders. The outcome was favorable with symptomatic treatment. CONCLUSION: A primary infection with CMV must be added to the diagnostic work-up in the presence of a febrile splenic infarction, especially when it is associated with a biological mononucleosis reaction.

Encapsulation capacity and natural payload delivery of an anticancer drug from boron nitride nanotube.

The behavior of confined anticancer carboplatin (CPT) molecules in a single (10, 10) boron nitride nanotube (BNNT) was studied by means of molecular dynamics simulations. Our study revealed a very large storage capacity of BNNT. Analysis of the energy profiles depending on the number of confined molecules, and on their spatial organization allowed us to quantify the ability of BNNT to vectorize CPT. Indeed, BNNT despite its small radius presented a large inner volume that favored stable encapsulation of multiple active anticancer molecules. Moreover, in our molecular dynamics simulations, the empty BNNT and the BNNT filled with CPT diffused spontaneously to the cell membrane and were able to passively enter inside lipid bilayers by a lipid-assisted mechanism. This property has been used to deliver naturally anticancer drugs to cellular targets. Using this enhanced drug delivery system, we have provided a definitive solution to the problem of drug release and have thus opened up a new way of targeting cancer cells. Indeed, regardless of the mode of action of the platinum complex towards the cell, the delivery of the drug on site should limit the side effects of the drug.

The protease activity of transthyretin reverses the effect of pH on the amyloid-ß protein/heparan sulfate proteoglycan interaction: a biochromatographic study.

Patients suffering of Alzheimer's disease (AD) are characterized by a low transthyretin (TTR) level in the brain. The effect of pH and TTR concentration in the medium on the ß-amyloid protein (Aß)/heparan sulfate proteoglycan (HSPG) association mechanism were studied using a biochromatographic approach. For this purpose, HSPG was immobilized via amino groups onto the amino propyl silica pre-packed column, activated with glutaraldehyde, by using the Schiff base method. Using an equilibrium perturbation method, it was clearly shown that Aß can be bound with HSPG. This approach allowed the determination of the thermodynamic data of this binding mechanism. The role of the pH was also analyzed. Results from enthalpy-entropy compensation and the plot of the number of protons exchanged versus pH showed that the binding mechanism was dependent on pH with a critical value at pH=6.5. This value agreed with a histidine protonation as an imidazolium cation. Moreover, the corresponding thermodynamical data showed that at pH>6.5, van der Waals and hydrogen bonds due to aromatic amino acids as tyrosine or phenylalanine present in the N-terminal (NT) part governed the Aß/HSPG association. Aß remained in its physiological structure in a random coil form (i.e. the non-amyloidogenic structure) because van der Waals interactions and hydrogen bonds were preponderant. At acidic pH (pH<6.5), ionic and hydrophobic interactions, created by histidine protonation and hydrophobic amino acids, appeared in the Aß/HSPG binding. These hydrophobic and ionic interactions led to the conversion of the random coil form of Aß into a ß-sheet structure which was the amyloidogenic folding. When TTR was incubated with Aß, the Aß/HSPG association mechanism was enthalpy driven at all pH values. The affinity of Aß for HSPG decreased when TTR concentration increased due to the complexation of Aß with TTR. Also, the decrease of the peak area with the increase of TTR concentration demonstrated that this Aß/TTR association led to the cleavage of Aß full length to a smaller fragment. For acidic pH (pH<6.5), it was shown that the importance of the hydrophobic and ionic interactions decreased when TTR concentration increased. This result confirmed that Aß was cleaved by TTR in a part containing only the NT part. Our results demonstrated clearly that TTR reversed the effect of acidic pH and thus played a protective role in AD.

Time course of odorant- and trigeminal-induced activation in the human brain: an event-related functional magnetic resonance imaging study.

It is well known that most odorants stimulate the trigeminal system but the time course of the brain regions activated by these chemical stimulations remains poorly documented, especially regarding the trigeminal system. This functional magnetic resonance imaging (fMRI) study compares brain activations resulting from the contrast between two odorant conditions (one bimodal odor and one relatively pure olfactory stimulant) according to the duration of the stimulation (i.e. one inhalation, or three or six successive inhalations). The results show striking differences in the main brain regions activated according to these durations. The caudate nucleus and the orbitofrontal cortex are only involved in short-duration stimulations, and the posterior insular cortex and post-central gyrus (SI) are only activated by long duration stimulations. Different regions of the frontal, temporal and occipital lobe are activated depending on the duration but mainly during medium-duration stimulations. These results expand on the findings of previous studies and contribute to the description of temporal networks in trigeminal perception.

[Chronic cough as the presenting feature of temporal arteritis]. / Toux chronique révélant une maladie de Horton.

We report a 70-year-old woman who presented with a chronic cough of 3-month duration, secondarily associated with fever and weight loss. She had no other symptoms. Physical examination was unremarkable and laboratory tests showed an increase level of acute phase reactants. Thoracic, abdominal and sinus computed tomographic scan was normal and bronchoscopy showed a non specific mucosa inflammation. Despite the absence of characteristic manifestations of temporal arteritis, a temporal artery biopsy was performed and disclosed evidence of typical temporal arteritis.

[Ascites with high protein concentration 2 months after C-section delivery: diagnosis using adenosine deaminase analysis combined with iconography]. / Ascite riche en protides survenant deux mois après un accouchement par césarienne: diagnostic par association du dosage de l'adénosine-désaminase et de l'imagerie.

We report the case of a 38-year-old woman, born and raised in Congo, in France for 7 years, who developed ascites 2 months after delivery by C-section. Thrombopenia at 95,000 elements per millimeter cube was diagnosed during her pregnancy and her obstetrician initiated a treatment with corticosteroids. Analysis of the ascitic fluid showed a high concentration of proteins (55.7 g/l), with 2000 elements, 80% of which were lymphocytes, and very high levels of adenosine deaminase. Thoracoabdominal tomodensitometry revealed ascites, a multinodular spleen, and hyperemia of the peritoneum; but the liver and the lungs were normal and no adenoma was identified. Laparoscopy was not performed and the suspected diagnosis of peritoneal tuberculosis was confirmed by only one culture of ascitic fluid.

[Hyperkalemia induced by atenolol]. / Hyperkaliémie secondaire à la prise d'aténolol.

We report a 53-year-old woman with hyperkaliemia secondary to treatment with atenolol. The diagnosis of atenolol induced hyperkaliemia was obtained after excluding other causes of hyperkaliemia and normalization of potassium serum level following the discontinuation of this medication without any other modification (treatment or diet). Furthermore, when atenolol was again introduced, serum potassium level increased and normalized when atenol was definitively discontinued. The mechanism of hyperkaliemia we suspected is probably a reduction of potassium intracellular transfer.

Assessment of effects of an additional dietary natural mineral water uptake on skin hydration in healthy subjects by dynamic barrier function measurements and clinic scoring.

BACKGROUND/AIMS: The skin protects the body's organs and tissues from damage and physical, chemical and bacteriological injuries. It also prevents the transcutaneous loss of water. The present study was conducted to assess the effects of additional dietary natural mineral water uptake on skin hydration and cutaneous well-being in subjects with dry skin. METHODS: Eighty subjects (44 women and 36 males, mean age 56+/-5.6 years) were included in the study, randomised per forearm and stratified by gender. Skin surface hydration, transepidermal water loss (TEWL), sorption-desorption test, skin colour, thickness and micro-relief were evaluated on the forearms. Clinical scoring of dryness, roughness and elasticity was performed by a dermatologist. RESULTS: An improvement of skin hydration was observed after additional water uptake, statistically modifying the hydration level as well as TEWL, the water-binding capacity of the uppermost layers of the stratum corneum. Improvements of softness, smoothness and skin-moisturising effect were perceived by healthy subjects, and skin micro-relief was improved. CONCLUSION: We suggest that natural mineral water supplementation may be used in order to improve the hydration of skin dryness as a complementary cosmetic approach.

Anisotropic photon migration in human skeletal muscle.

It is demonstrated in the short head of the human biceps brachii of 16 healthy subjects (12 males and 4 females) that near infrared photon migration is anisotropic. The probability for a photon to travel along the direction of the muscle fibres is higher (approximately 0.4) than that of travelling along a perpendicular axis (approximately 0.3) while in the adipose tissue the probability is the same (approximately 0.33) in all directions. Considering that the muscle fibre orientation is different depending on the type of muscle considered, and that inside a given skeletal muscle the orientation may change, the present findings in part might explain the intrasubject variability observed in the physiological parameters measured by near infrared spectroscopy techniques. In other words, the observed regional differences might not only be physiological differences but also optical artefacts.

[Interest of performing systematically the protein profile in an internal medicine department. National survey and prospective study on 229 admissions]. / Intérêt de la réalisation systématique du profil protéique d'orientation dans un service de médecine interne. Enquête nationale des pratiques et étude prospective sur 229 admissions.

INTRODUCTION: Despite a wide national use, the usefulness of the protein profile has only been evaluated in a small number of studies, essentially in patients with unknown diagnoses. METHODS: We conducted a survey on 339 french internal medicine departments to evaluate how the protein profile was used in these services. Concomitantly we achieved a prospective study on 229 patients in our department, with a mean follow up of 9 months, to evaluate how did the protein profile influence the diagnosis process. RESULTS: We received 183 responses to our national survey: the protein profile was available in 110/183 (60%) departments with 94/110 (85%) using it during hospitalisation and 20/94 (21.3%) using it systematically. Among the 229 protein profile analysed in our department, 44 (19.2%) were considered useful with 20 (8.7%) of them allowing the diagnosis of a new pathology. If the profile had not been done systematically, the physicians of our department would have performed the profile in 102/229 (44.5%) cases, whereas seven (3%) useful profiles would not have been done. CONCLUSION: We think that the profile has a consistent interest in hospitalized patients with a known or unknown pathology but performing systematically such a test appears to be of limited benefit.

Culture of neural cells on polymers coated surfaces for biosensor applications.

We focused our study on the olfactory cells growth on biocompatible polymer films electrodeposited on a silicon microsystem. Several substrates such as polyethyleneimine (PEI), polypropyleneimine (PPI), and polypyrrole (PPy), acting as potentially good candidates for cell culture, were tested in order to allow cells to adhere and proliferate. During their growth, the evolution of their morphology was monitored using both confocal microscope and immunohistochemistry, leading to the conclusion of a normal development. An estimation of the adhesion and proliferation rates of rat neuronal cell cultures indicated that PEI and PPI were the best substrates for cultivating olfactory cells.

The first experience of a dedicated biomedical education unit at the university of franche-comté.

Biomedical activity is rapidly expanding. Actually, the demand for hi-tech technologies in health is in constant increase. At the Franche-Comté High Institute of Engineers (ISIFC) an engineer can acquire the knowledge and skills to carry out various tasks in biomedical engineering field including academic research, in-hospital devices maintenance or industrial development. The main advantage of the ISIFC is that it offers an exceptional multidisciplinary programme thank to close cooperation between Besançon University Hospital professionals and Engineering Sciences professors and researchers. As a result, the graduates obtain real experience in the both fields. The majority of the ISIFC engineers are employed by firms producing and/or commercializing health-oriented materials and equipments such as Alcis, Arthesis, Aventis Pasteur, Biomérieux, Imasonic, Medos, Statice Santé, Sophysa, Symbios, Praxim, Protheos, Tornier, Zimmer etc.

Comparing the contractile properties of human fibroblasts in leg ulcers with normal fibroblasts.

OBJECTIVE: The tissue contraction phenomenon associated with wound healing is of prime importance for wound closure. Contractile properties of human fibroblasts from chronic venous leg ulcers were compared with those of normal fibroblasts using in vitro models. METHOD: Biopsies were taken from the uninvolved skin of the thigh, the epithelialised ulcer edge and the non-epithelialised ulcer centre in four patients (average age: 78 years). Fibroblasts were obtained by an explant technique and expanded in vitro in Dulbecco's Modified Eagle's Medium supplemented with 10% foetal calf serum and used for the assays at their fourth passage. Intracellular alpha-smooth muscle actin expression (alphaSM-actin) was studied by immunofluorescence labelling of cells cultured in monolayer. Contractile properties were evaluated using three-dimensional collagen lattices. RESULTS: Fibroblasts from the ulcer centre were the richest cells in actin filaments. Both populations of venous ulcer fibroblasts contracted more rapidly and to a greater extent than normal fibroblasts. The peak contractile forces developed by fibroblasts from the ulcer centre and the ulcer edge were 30% and 18% greater than normal fibroblasts respectively. CONCLUSION: Some functions of fibroblasts, in particular the generation of contractile forces and the formation of cytoplasmic actin filaments, seem not to be affected in chronic venous ulcers. DECLARATION OF INTEREST: This study was supported by the Fondation Coloplast pour la Qualite de la Vie of France.

New fluorescence imaging probe with high spatial resolution for in vivo applications.

A new fiberized fluorescence imaging probe is presented. This device can potentially be used for a wide range of biological or medical applications. By exploiting the chromatic aberrations of gradient index lenses, the excitation blue or near-UV excitation light is focused on the sample surface, while the red fluorescence signal is efficiently launched back to collecting fibers. The excitation fiber is single mode at the working wavelength so that a resolution of 5 microm is obtained over a scanning area of several square millimeters. Experimental fluorescence images are presented. They concern either self-fabricated fluorescent microsamples or views of leaves that constitute an example of biological tissues analysis. The probe can also be adapted for spectroscopic investigations.

Adhesion and proliferation of cells on new polymers modified biomaterials.

Up to today, several techniques have been used to maintain cells in culture for studying many aspects of cell biology and physiology. More often, cell culture is dependent on proper anchorage of cells to the growth surface. Poly-l-lysine is commonly used as adhesive molecule. In this study, we present, as an alternative to poly-l-lysine, new polymer film substrates, realized by electropolymerization of different monomers on fluorine-doped tin oxide (FTO) surfaces since electropolymerization is a good method to coat selectively metallic or semiconducting electrodes with polymer films. So, the adhesion, proliferation and morphology of rat neuronal cell lines were investigated on polymer treated surfaces. Several amine-based biocompatible polymers were tested: polyethyleneimine (PEI), polypropyleneimine (PPI), polypyrrole (PPy) and poly(p-phenylenediamine) (PPPD). These polymer films were coated on FTO surfaces by electrochemical oxidation. After 8 h in a culture medium, a high percentage of cells was found to be attached to PEI and PPI compared to the other polymers and to the reference surfaces (glass and FTO uncovered). After 24 and 72 h in the culture medium, cells were found to proliferate faster on PEI and PPI than on other polymers and reference surfaces. Consequently, cells have a greater fold expansion on PEI and PPI than on PPPD, PPy or glass and FTO uncoated. From these results, we deduce that PEI and PPI can be useful as coating surface to cultivate neuronal cells.

Laser-diode interferometric heterodyne vibrometer: application to linear motor control.

We describe an interferometric heterodyne vibrometer that uses a laser diode with a triangular modulation frequency. This optical sensor is used to probe a vibrating polished surface. As an illustration of the sensor performance, the control of nonuniform velocity of a linear motor is achieved. The technique can be used over a large bandwidth between a few hertz and several tens of kilohertz. Generalization of the technique to the sensing of frequency vibrations is also demonstrated theoretically.

Optical near-field data analysis through time-frequency distributions: application to the characterization and separation of the image spectral content by reassignment.

The near-field optical images have been traditionally analyzed by Fourier analysis and, recently, by wavelet analysis. Those data are nonstationary, which means that their spectral content varies with time, owing to the scanning-probe recording process; therefore time-frequency representations are, potentially, powerful tools for local characteristics extraction or shape separation, since they distribute the energy of the analyzed signal over the time and frequency variables and faithfully depict the signal local behavior. In this study we show that Cohen's class time-frequency distributions and their modified version by the reassignment method are appropriate tools for the analysis of near-field optical data. We demonstrate this by using these tools first on simulated data and second on experimental near-field optical images. Within this context we observe that time-frequency analysis allows one to easily characterize local frequencies, which involves a possible separation of relevant optical signal from artifacts.

[Study of anemia in giardiasis intestinalis in Tunisian preschool children]. / Etude de l'anemie au cours de la giardiase chez des enfants Tunisiens d'age prescolaire.

The present work is based upon a prospective in study done in a semi-urban area of suburbs of Tunis, from february to November 1997. A total of 302 children aged between 6 month to 5 years were enrolled in the survey. The study aimed at assessing the extention of parasitoses in preschool aged children. The relationship between the Giardiasis intestinalis and ferropenic anemia. The prevalence of anemia is 31.78% (n = 302). The parasitologic analysis has shown that 113 children out of 302 are infected; 37.41%. We observed an obvious predominance of Giardia Lamblia: 62% (n = 113) pathogenic protozoon. The rate of anemia parasited children is amounted to 19.78%. During the Giardiasis, anemia is present in 23.17% of the cases. The Polyparasitism concerns 16% of the infested children. This anemia could be caused by a global bad absorption syndrome or by a ferro-elective bad absorption. A proper sanitary education, a purification action and also a curative treatment of the beaners carriers will be the only guarantees to decrease its morbidity.

Local spectral information in the near field with wavelet analysis and entropy.

In near-field optical microscopy the resolution is strongly related to the experimental illumination conditions and to the separation between tip and sample. Therefore the spectral information in near-field data (related to the resolution in images) can be described only locally as a function of the tip-sample position. To make a local study of the spectral information in near-field data, we use wavelet decomposition that is associated with the calculation of entropy. We deduce the resolution from the characteristics of the wavelet, which leads to an automatic and numerical evaluation of the resolution in near-field data.