[Autism spectrum disorder : ethiopathogenesis and benefits of early diagnosis]. / Trouble du spectre autistique : étiopathogénie et intérêt d'un diagnostic précoce.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that manifests in altered or reduced social behaviours, social communication disorders, and repetitive behaviours and/or restricted interests. The etiology of ASD is complex and multifactorial. The etiopathogenesis of the disorder is multiple, including brain abnormalities, visual contact and early interaction disorders. These signs are often the focus of parental concerns. In addition, since ASD is neurodevelopmental, all signs are not always present simultaneously. Indeed, they appear progressively, until the age of 3 years, at which the diagnosis can usually be made. Nevertheless, in more complex cases, this diagnosis may be considered later. The first signs of ASD (before 24 months) will be addressed because they are crucial for an early diagnosis. Their knowledge allows the establishment of a follow-up as well as its quick specific care. Indeed, by acting during a developmental period when brain plasticity is high, early intervention allows to modify the evolution of symptoms, and later on to limit secondary handicaps.

Le trouble du spectre de l'autisme (TSA) est un trouble neurodéveloppemental qui se manifeste par des comportements sociaux altérés ou réduits, des troubles de la communication sociale ainsi que des comportements répétitifs et/ou intérêts restreints. L'étiologie du TSA est complexe et multifactorielle. Les étiopathogénies du trouble mises en avant sont multiples. On y retrouve, entre autres, des anomalies cérébrales, des anomalies du contact visuel et des troubles des interactions précoces. Ces signes font souvent l'objet des préoccupations parentales. En outre, le TSA étant neurodéveloppemental, l'ensemble des signes ne sont pas toujours présents d'emblée. En effet, ils apparaissent progressivement, jusqu'à l'âge de 3 ans, moment à partir duquel le diagnostic peut généralement être posé. Néanmoins, dans des cas plus complexes, ce diagnostic peut être envisagé de manière plus tardive. Les premiers signes du TSA (avant 24 mois) seront abordés car ils sont au cœur de l'enjeu du diagnostic précoce. Leur connaissance permet la mise en place d'un suivi et d'une prise en charge rapide. En effet, en agissant au cours d'une période développementale où la plasticité cérébrale est élevée, l'intervention précoce permet de modifier l'évolution des symptômes et, a posteriori, de limiter les handicaps secondaires.

Self-assembling peptide/thermoresponsive polymer composite hydrogels: effect of peptide-polymer interactions on hydrogel properties.

We have investigated the effect of doping the self-assembling octapeptide FEFEFKFK (F, phenylalanine; E, glutamic acid; K, lysine) hydrogels with various amounts of thermoresponsive conjugate of FEFEFKFK and poly(N-isopropylacrylamide) (PNIPAAm) in order to create novel hydrogels. The samples were characterized using a range of techniques including microdifferential scanning calorimetry (µDSC), oscillatory rheology, transmission electron microscopy (TEM), atomic force microscopy (AFM), and small angle neutron scattering (SANS). The peptide from the conjugate was shown to be incorporated into the peptide fiber, resulting in the polymer being anchored to the peptide fiber. The conjugation of the polymer to the peptide and its anchoring to the peptide fibers did not affect its lower critical solution temperature (LCST). On the other hand, it did result in a decrease in the LCST enthalpy and a significant increase in the G' of the hydrogels, suggesting the presence of hydrogen bond interactions between the peptide and the polymer. As a result, the polymer was found to adopt a fibrillar arrangement tightly covering the peptide fiber. The polymer was still found to go through a conformational change at the LCST, suggesting that it collapses onto the peptide fiber. On the other hand, the fibrillar network was found to be mainly unaffected by the polymer LCST. These changes at the LCST were also found to be fully reversible. The nature of the interaction between the polymer and the peptide was shown to have a significant effect on the conformation adopted by the polymer around the fibers and the mechanical properties of the hydrogels.

Immobilization of cell-binding peptides on poly-ε-caprolactone film surface to biomimic the peripheral nervous system.

Cell-material interactions are crucial for cell adhesion and proliferation on biomaterial surfaces. Immobilization of biomolecules leads to the formation of biomimetic substrates, improving cell response. We introduced RGD (Arg-Gly-Asp) sequences on poly-ε-caprolactone (PCL) film surfaces using thiol chemistry to enhance Schwann cell (SC) response. XPS elemental analysis indicated an estimate of 2-3% peptide functionalization on the PCL surface, comparable with carbodiimide chemistry. Contact angle was not remarkably reduced; hence, cell response was only affected by chemical cues on the film surface. Adhesion and proliferation of Schwann cells were enhanced after PCL modification. Particularly, RGD immobilization increased cell attachment up to 40% after 6 h of culture. It was demonstrated that SC morphology changed from round to very elongated shape when surface modification was carried out, with an increase in the length of cellular processes up to 50% after 5 days of culture. Finally RGD immobilization triggered the formation of focal adhesion related to higher cell spreading. In summary, this study provides a method for immobilization of biomolecules on PCL films to be used in peripheral nerve repair, as demonstrated by the enhanced response of Schwann cells.

Essential oils and low-intensity electromagnetic pulses in the treatment of androgen-dependent alopecia.

This double-blind randomized study vs placebo in healthy male and female volunteers demonstrates the positive biologic effect on hair loss and hair regrowth of a pulsed electromagnetic field in combination with essential oils administered according to a regular treatment schedule of 26 weeks. Mean hair count comparisons within the groups significantly favor the treatment group, which exhibited a decrease in hair loss in 83% of the volunteers and a more than 20% hair count increase over baseline in 53% of patients. The process exhibited no side effects or untoward reactions. The histologic examination correlated with the clinical study. A parallel immunohistochemical examination showed an increase in the proliferation index, and when the expression of Ki67 (a cell proliferation marker) is increased, the mitoses are barely visible in the histologic examination. The rationale of this phenomenon is considered to be due to an electrophysiologic effect on the quiescent hair follicle.

Coexistence of liquid and solid phases in flowing soft-glassy materials.

Magnetic-resonance-imaging rheometrical experiments show that concentrated suspensions or emulsions cannot flow steadily at a uniform rate smaller than a critical value (gamma(c)). As a result, a "liquid" region (sheared rapidly, i.e., at a rate larger than gamma(c)) and a "solid" region (static) coexist. The behavior of the fluid in the liquid region follows a simple power-law model, while the extent of the solid region increases with the degree of jamming of the material.

Capillary condensation in a fractal porous medium.

Small-angle x-ray and neutron scattering are used to characterize the surface roughness and porosity of a natural rock which are described over three decades in length scales and over nine decades in scattered intensities by a surface fractal dimension D = 2.68+/-0.03. When this porous medium is exposed to a vapor of a contrast-matched water, neutron scattering reveals that surface roughness disappears at small scales, where a Porod behavior typical of smooth interfaces is observed instead. Water-sorption measurements confirm that such interface smoothing is due predominantly to the water condensing in the most strongly curved asperities rather than covering the surface with a wetting film of uniform thickness.

A NMR investigation of adsorption/desorption hysteresis in porous silica gels.

The purpose of this study is to investigate possible differences in geometry and connectivity of the liquid phase in a partially water-satured porous medium between the adsorption and the desorption branches, using a series of silica gels. This was done by comparing the T1 and T2 relaxation times (in 1H and 2H nuclear magnetic resonance (NMR) relaxation) as well as the water self-diffusion coefficient D (in 1H) along the two branches of the adsorption/desorption isotherms. The results show that the two relaxation times and the diffusion coefficient are strongly dependent on the water content (saturation level). When plotted in normalized coordinates, the T1 and T2 vs. P/Po curves fit closely the adsorption/desorption isotherms, which validates the two-population, fast-exchange model. Furthermore, because at equivalent saturation levels, there is no difference between the relaxation times and diffusion coefficients obtained along the adsorption branch and those obtained along the desorption branch, one is led to the conclusion that despite different equilibrium conditions, the geometry and connectivity of the liquid phase are statistically the same along the two branches.

Advantage of the presence of living dermal fibroblasts within in vitro reconstructed skin for grafting in humans.

Methods for serial cultivation of human keratinocytes can provide large quantities of epidermal cells, which have the potential of restoring the vital barrier function of the epidermis in extensive skin defects such as burns. To investigate the value of combining an epidermis with a dermal component, fibroblasts originated from the superficial dermis were used to seed a collagen lattice as described by E. Bell (dermal equivalent). Beginning in 1981, we grafted 18 patients (burns and giant nevi) using 35 grafts 10 x 10 cm in size. In the course of this work, the original technique was modified and improved as experience was gained. We began by using small skin biopsy samples as a source of keratinocytes cultured on a dermal equivalent before grafting in a one-step procedure, but this gave poor cosmetic results, because of a nonhomogeneous epidermalization. We then chose to cover the graft bed using a two-step procedure. The first step consisted of grafting a dermal equivalent to provide a dermal fibroblast-seeded substrate for subsequent in vivo epidermalization by cultured epidermal sheets. Whatever the epidermalization technique used, a living dermal equivalent applied to the graft bed was found to reduce pain, to provide good hemostasis, and to improve the mechanical and cosmetic properties of the graft. A normal undulating dermal-epidermal junction reappeared by 3 to 4 months after grafting and elastic fibers were detectable 6 to 9 months after grafting. As a result of the biosynthesis of these products, the suppleness (e.g., elasticity) of the grafts was closer to that of normal skin than the cicatricial skin usually obtained with epidermal sheets grafted without the presence of living dermal cells. This rapid improvement of the mechanical properties of the graft could be attributed to the presence of fibroblasts cultured from the dermis and seeded into the collagen matrix.

Measuring urinary protein with the new BioRad reagent kit: evaluation and comparison with five other methods.

Total urinary protein was measured by five methods: BioRad Total Protein Test (TPT), pyrogallol red, benzethonium chloride, sulfosalicylic acid, trichloroacetic acid, and the results compared to those obtained by a method combining preparative ultrafiltration and the biuret reaction. TPT was linear to 1.5 g protein/l, the detection limit 0.0135 g/l, and it was 3-5 times more sensitive than the other methods. Within-day precision (CV) was 4.3%, (0.60 g/l), the day-to-day precision was 4.5%. The protein contents of 35 selected urine samples assigned to one of five groups according to their electrophoretic pattern were assayed by the five methods. No method accurately measured physiological proteinuria, but the values for light chain (Bence Jones), glomerular, tubular and overload proteinurias measured by TPT did not differ significantly from the biuret value. The other methods differed significantly for at least three groups. Alpha 1 acid glycoprotein slightly inhibited TPT, but peptones, amino acids, antibiotics or normal urine constituents had little or no effect. The TPT method has been automated (Kone Progress); normal 24-h urinary protein excretion was 36 mg/day (range 12-114), the protein creatinine ratio was 34 mg/g (12-106 mg/g).

High serum procalcitonin concentrations in patients with sepsis and infection.

High concentrations of calcitonin-like immunoreactivity have been found in the blood of patients with various extrathyroid diseases. By means of a monoclonal immunoradiometric assay for calcitonin precursors, we have measured serum concentrations of procalcitonin in patients with various bacterial and viral infections. 79 children (newborn to age 12 years) in hospital with suspected infections were investigated prospectively. 19 patients with severe bacterial infections had very high serum concentrations of procalcitonin at diagnosis (range 6-53 ng/mL) in comparison with 21 children found to have no signs of infection (baseline concentrations < 0.1 ng/mL). Serum procalcitonin values decreased rapidly during antibiotic therapy. 11 patients with peripheral bacterial colonisation or local infections without invasive sepsis and 18 (86%) of 21 patients with viral infections had concentrations within or slightly above the normal range (0.1-1.5 ng/mL). Among 9 severely burned patients studied in an intensive care unit, the post-traumatic course of procalcitonin concentrations (range 0.1-120 ng/mL) was closely related to infectious complications and acute septic episodes. Concentrations of mature calcitonin were normal in all subjects, whatever procalcitonin concentrations were found. Concentrations of a substance immunologically identical to procalcitonin are raised during septic conditions. Serum concentrations seem to be correlated with the severity of microbial invasion.

European comparative clinical study of Inerpan: a new wound dressing in treatment of partial skin thickness burns.

Eleven European burns centres in five countries (Belgium, England, Germany, Italy, Switzerland) participated in a prospective, randomized clinical trial comparing a new wound dressing Inerpan with conventional dressings such as petroleum jelly gauze, petroleum jelly gauze with antibiotics and silver sulphadiazine cream. The indication was partial skin thickness burns and 62 patients were included. In each patient, two similar lesions (with respect to depth and surface area) were compared, one being treated with Inerpan, the other one with a control dressing. The following parameters were studied: healing time, quality of healing, intensity of pain, local tolerance and frequency of dressing changes. Analysis of the results showed that Inerpan-treated sites healed faster than conventional ones, and were associated with a highly significant reduction of pain. The frequency of dressing changes was greatly reduced and the local tolerance was good.

Effect of platelet-activating factor on tumor necrosis factor-induced superoxide generation from human neutrophils. Possible involvement of G proteins.

The effect of platelet-activating factor (PAF) and of two specific PAF antagonists on tumor necrosis factor (TNF) induced superoxide production by human polymorphonuclear neutrophils (PMN) was examined. PAF alone (0.1 pM to 0.1 nM) failed to evoke superoxide production; however, when PAF was added for 10 min to cells upon prior incubation with 10 ng/mL TNF for 50 min, superoxide production was significantly enhanced as compared to that induced by TNF alone. Maximum amplification (+30%) was obtained with 10 pM PAF; however, the effect was completely abolished by two structurally unrelated PAF antagonists, BN 52021 and BN 52111. The antagonists also decreased by 25% the superoxide production elicited solely by TNF, implicating the involvement of endogenous PAF in this process. Pretreatment of the PMN with either pertussis or cholera toxin attenuated the PAF amplified superoxide production in TNF stimulated cells, suggesting that G proteins sensitive to these toxins may be involved in the mechanisms controlling amplification.

Tumor necrosis factor alpha 'primes' the platelet-activating factor-induced superoxide production by human neutrophils: possible involvement of G proteins.

It has recently been demonstrated that very low concentrations of platelet-activating factor (PAF) and various cytokines can prime human neutrophils (PMN) to respond in an enhanced manner to subsequent agonistic stimulation. We were interested to ascertain whether superoxide generation by human PMN could be amplified by PAF following initial stimulation with tumor necrosis factor (TNF) and the effect of cholera and pertussis toxin on this process. PAF alone (0.1 pM-0.1 nM) failed to evoke any superoxide production; however, when PAF was added for 10 min to cells previously incubated for 50 min with 10 ng/ml TNF, superoxide production was significantly enhanced relative to that induced by TNF alone. Maximum amplification (+30%) was obtained with 10(-12) M PAF, this effect being completely abolished by BN 52021 and BN 52111, two structurally unrelated PAF antagonists. The PAF antagonists also decreased by 25% the superoxide production elicited solely by TNF, indicating that TNF-induced superoxide generation is partially mediated by a mechanism involving endogenous PAF. Pretreatment of the PMN with pertussis or cholera toxin reduced the amplification of superoxide production induced by PAF in TNF-stimulated PMN, implicating pertussis and cholera toxin-sensitive G-proteins in the amplification process.

Optimized microturbidimetric assay for fibrinogen.

In this assay we measure the turbidity produced by precipitation of plasma fibrinogen with a reagent composed of ammonium sulfate, EDTA, and guanidine hydrochloride. The two-step reagent addition, and use of fixed reaction times, eliminates interference from bilirubin, hemoglobin, and chylomicrons. We checked 135 monoclonal proteins for interference, finding the probability of encountering major interference in samples from adults to be very low, P = 0.0002. The method is calibrated with purified fibrinogen and the response is linear over the range 0-10 g/L. Within-run precision (CV) is less than 2% from 1 to 10 g/L. Correlations with the immunoturbidimetric (r = 0.99), chronometric (r = 0.99), and clotting (r = 0.97) methods were extremely high.