Crocin, a natural molecule with potentially beneficial effects against skin ageing.

OBJECTIVE: Oxidative stress and low-grade chronic inflammation stand out as key features of physiological skin ageing. The aim of this study was to examine in normal human epidermal keratinocytes (NHEK) and human dermal fibroblasts (HDF) grown in vitro, the antioxidant and anti-inflammatory properties of crocin, a carotenoid glycoside responsible for the colour of saffron. Moreover, considering the newly emerging field of skin glycobiology and the presence of two gentiobiosyl moieties in crocin, the effect of crocin on NHEK glycosylation pathways was for the first time investigated. METHODS: The anti-inflammatory and antioxidant activities of crocin were evaluated by in vitro assays of antioxidation activities, ELISA and microarray analysis. The effect of crocin on keratinocyte glycobiology was evaluated by proprietary GLYcoDiag lectin technologies and microarray analysis. RESULTS: Crocin is endowed with antioxidant potential against reactive oxygen species, protects squalene against UVA-induced peroxidation and prevents the release of inflammatory mediators. The expression of NF-kB-related genes and glycosylation-related genes is modulated in the presence of crocin. CONCLUSION: Results could designate this molecule as a promising skin ageing prevention cosmetic agent. Of note, some of these effects could be mediated by protein O-glycosylation and interaction of crocin with osidic receptors of keratinocytes.

On the use of X-ray absorption spectroscopy to elucidate the structure of lutetium adenosine mono- and triphosphate complexes.

Although the physiological impact of the actinide elements as nuclear toxicants has been widely investigated for half a century, a description of their interactions with biological molecules remains limited. It is however of primary importance to better assess the determinants of actinide speciation in cells and more generally in living organisms to unravel the molecular processes underlying actinide transport and deposition in tissues. The biological pathways of this family of elements in case of accidental contamination or chronic natural exposure (in the case of uranium rich soils for instance) are therefore a crucial issue of public health and of societal impact. Because of the high chemical affinity of those actinide elements for phosphate groups and the ubiquity of such chemical functions in biochemistry, phosphate derivatives are considered as probable targets of these cations. Among them, nucleotides and in particular adenosine mono- (AMP) and triphosphate (ATP) nucleotides occur in more chemical reactions than any other compounds on the earth's surface, except water, and are therefore critical target molecules. In the present study, we are interested in trans-plutonium actinide elements, in particular americium and curium that are more rarely considered in environmental and bioaccumulation studies than early actinides like uranium, neptunium and plutonium. A first step in this strategy is to work with chemical analogues like lanthanides that are not radioactive and therefore allow extended physical chemical characterization to be conducted that are difficult to perform with radioactive materials. We describe herein the interaction of lutetium(III) with adenosine AMP and ATP. With AMP and ATP, insoluble amorphous compounds have been obtained with molar ratios of 1:2 and 1:1, respectively. With an excess of ATP, with 1:2 molar ratio, a soluble complex has been obtained. A combination of spectroscopic techniques (IR, NMR, ESI-MS, EXAFS) together with quantum chemical calculations has been implemented in order to assess the lutetium coordination arrangement for the two nucleotides. In all the complexes described in the article, the lutetium cation is coordinated by the phosphate groups of the nucleotide plus additional putative water molecules with various tridimensional arrangements. With AMP 1:2 and ATP 1:1 solid-state compounds, polynuclear complexes are assumed to be obtained. In contrast, with ATP 1:2 soluble compound, the Lu coordination sphere is saturated by two ATP ligands, and this favors the formation of a mononuclear complex. In order to further interpret the EXAFS data obtained at the Lu LIII edge, model structures have been calculated for the 1:1 and 1:2 ATP complexes. They are discussed and compared to the EXAFS best fit metrical parameters.

Pleth variability index is a weak predictor of fluid responsiveness in patients receiving norepinephrine.

BACKGROUND: In patients receiving an infusion of norepinephrine, the relationship between the amplitude of the oximeter plethysmographic waveform and stroke volume may be variable and quality of the waveform might be reduced, compared with patients not receiving norepinephrine. We assessed the reliability of the pleth variability index (PVI), an automatic measurement of the respiratory variation of the plethysmographic waveform, for predicting fluid responsiveness in patients receiving norepinephrine infusions. METHODS: We measured the response of cardiac index (transpulmonary thermodilution) to i.v. fluid administration in 42 critically ill patients receiving norepinephrine. Patients with arrhythmias, spontaneous breathing, tidal volume <8 ml kg(-1), and respiratory system compliance <30 ml cm H(2)O(-1) were excluded. Before fluid administration, we recorded the arterial pulse pressure variation (PPV) and pulse contour analysis-derived stroke volume variation (SVV, PiCCO2) and PVI (Masimo Radical-7). RESULTS: In seven patients, the plethysmographic signal could not be obtained. Among the 35 remaining patients [mean SAPS II score=77 (sd=17)], i.v. fluid increased cardiac index ≥15% in 15 'responders'. A baseline PVI ≥16% predicted fluid responsiveness with a sensitivity of 47 (inter-quartile range=21-73)% and a specificity of 90 (68-99)%. The area under the receiver operating characteristic curve was significantly lower for PVI [0.68 (0.09)] than for PPV and SVV [0.93 (0.06) and 0.89 (0.07), respectively]. Considering all pairs of measurements, PVI was correlated with PPV (r(2)=0.27). The fluid-induced changes in PVI and PPV were not significantly correlated. CONCLUSIONS: PVI was less reliable than PPV and SVV for predicting fluid responsiveness in critically ill patients receiving norepinephrine. In addition, PVI could not be measured in a significant proportion of patients. This suggests that PVI is not useful in patients receiving norepinephrine.

Time-resolved investigation of nanometer scale deformations induced by a high flux x-ray beam.

We present results of a time-resolved pump-probe experiment where a Si sample was exposed to an intense 15 keV beam and its surface monitored by measuring the wavefront deformation of a reflected optical laser probe beam. By reconstructing and back propagating the wavefront, the deformed surface can be retrieved for each time step. The dynamics of the heat bump, build-up and relaxation, is followed with a spatial resolution in the nanometer range. The results are interpreted taking into account results of finite element method simulations. Due to its robustness and simplicity this method should find further developments at new x-ray light sources (FEL) or be used to gain understanding on thermo-dynamical behavior of highly excited materials.

Mixed acoustic phonons and phase modes in an aperiodic composite crystal.

Aperiodic crystals which are long range ordered materials present original dynamics features due to the lack of translational symmetry formally implying the nonvalidity of the Brillouin zone concept. This Letter reports the observation by neutron scattering of an overdamped acousticlike mode at a Bragg peak position in a n-alkane-urea inclusion crystal. This result implies the existence of a gap in the dispersion branch. The gap and anomalous damping of these collective modes are discussed in terms of specific dynamics and interaction in aperiodic materials.

Confined linear molecules inside an aperiodic supramolecular crystal: the sequence of superspace phases in n-hexadecane/urea.

High-resolution studies of the host-guest inclusion compound n-hexadecane/urea are reported at atmospheric pressure, using both cold neutrons and x-ray diffraction. This intergrowth crystal presents a misfit parameter, defined by the ratio c(h)/c(g) (c(host)/c(guest)), which is temperature independent and irrational (γ = 0.486 ± 0.002) from 300 to 30 K. Three different structural phases are reported for this aperiodic crystal over this temperature range. The crystallographic superspaces are of rank 4 in phases I and II, whereas phase III is associated with an increase in rank to 5, with a supplementary misfit parameter (δ = 0.058 ± 0.002) that is constant throughout this phase. The superspace group of phase I is hexagonal P6(1)22(00γ) down to T(c1) = 149.5 ± 0.5 K; phase II, which persists down to T(c2) = 127.8 ± 0.5 K is orthorhombic P2(1)2(1)2(1)(00γ), and phase III is orthorhombic P2(1)2(1)2(1)(00γ)(00δ).

Observations on use of montelukast in pediatric eosinophilic esophagitis: insights for the future.

Eosinophilic esophagitis is characterized by dense infiltration of the esophageal epithelium with eosinophils, typically accompanied by dysphagia. Effective therapies include the use of topical and systemic steroids as well as elimination diets. No previous reports have described the use of montelukast in the management of pediatric eosinophilic esophagitis. We retrospectively reviewed the charts of all patients with eosinophilic esophagitis followed in our pediatric center between 2000 and 2009. Those treated with montelukast were studied in detail. Study outcome was clinical response rate, defined by symptom (not histologic) improvement. Twenty-one patients with eosinophilic esophagitis were identified. Eight patients were maintained on montelukast (range 4-10 mg daily) after confirming the diagnosis of eosinophilic esophagitis histologically and failing to respond to a trial of proton pump inhibitor therapy. Three of eight patients had a clinical response (one had complete response and two with partial response) that could be attributed to montelukast. Four other patients responded clinically, but other therapies were concomitantly implemented. No side effects were reported with montelukast treatment with a mean follow-up duration of 32 months. Five patients had remained on montelukast therapy at the time of the final follow-up. Montelukast has minimal risk of adverse reactions compared with steroid therapy and may offer clinical relief in a small subset of children with eosinophilic esophagitis. Histologic response could not be verified in this study. Prospective studies, using higher montelukast doses, may potentially play a role and should be considered for future investigation.

Strain wave pathway to semiconductor-to-metal transition revealed by time-resolved X-ray powder diffraction.

One of the main challenges in ultrafast material science is to trigger phase transitions with short pulses of light. Here we show how strain waves, launched by electronic and structural precursor phenomena, determine a coherent macroscopic transformation pathway for the semiconducting-to-metal transition in bistable Ti3O5 nanocrystals. Employing femtosecond powder X-ray diffraction, we measure the lattice deformation in the phase transition as a function of time. We monitor the early intra-cell distortion around the light absorbing metal dimer and the long range deformations governed by acoustic waves propagating from the laser-exposed Ti3O5 surface. We developed a simplified elastic model demonstrating that picosecond switching in nanocrystals happens concomitantly with the propagating acoustic wavefront, several decades faster than thermal processes governed by heat diffusion.

Evaluation of PCR-DGGE methodology to monitor fungal communities on grapes.

AIMS: Some fungi present on the surface of grapes may have a negative effect on the quality of wine. The aim of this study was to evaluate PCR-denaturing gradient gel electrophoresis (PCR-DGGE), for the establishment of fungal community profiles from grapes, in order to monitor fungi potentially involved in wine defects. METHODS AND RESULTS: A fragment of the beta-tubulin gene was amplified from filamentous fungi and yeasts described from grapes and analysed using two different denaturing gradient gels to constitute a reference database. The use of beta-tubulin sequences instead of ITS rDNA in PCR-DGGE showed a progress in the discrimination of these fungal species but comigration problems were still observed. The technique was then applied on grape samples. The profiles counted up to 10 bands of which half corresponded to species which were not recorded in the reference database. CONCLUSION: PCR-DGGE represents a useful tool to compare environmental samples for the study of the dynamics of fungal communities, but comigrations represent a limit in its use to describe the species present. SIGNIFICANCE AND IMPACT OF THE STUDY: A better knowledge of the fungal diversity on grapes, particularly species responsible for wine defect, is necessary to develop accurate molecular detection tools.

Wheat flour allergy: an entire diagnostic tool for complex allergy.

Wheat proteins are involved in respiratory allergy, contact allergy and food allergy. Wheat allergens involve in these pathologies are well-known. However, establishment of wheat allergy diagnostic can be sometimes difficult on account of the complex allergenic composition of skin prick test (SPT) solutions of wheat flour. Therefore, we have studied specific IgE reactivity from patient sera with wheat food allergy, and characterized allergenic composition of wheat SPT solutions by specific antibodies directed to wheat allergens. The results showed that 20 of the 25 sera analyzed contained specific IgE to at least one wheat protein fraction. Among positive sera, 75% have specific IgE to water/salt soluble fraction, 85% to native gluten fractions and 65% to wheat isolate fraction. The results showed also that SPT solutions of wheat flour contained major food allergens from each allergenic fraction. These results highlighted the importance of using fractions, which constitute the whole wheat allergenic pattern, during specific IgE reactivity analyses. Moreover, we have observed that wheat isolate extract (results of food industrial process) contained not only modified allergens (neo-allergens) involve of specific food allergy to wheat isolate but also some native allergens involve in wheat food allergy. Thus, these results showed the importance to use, for wheat in vivo diagnosis together wheat SPT solutions (gluten extract and wheat isolate) in order to differentiate wheat food allergy to specific wheat isolate allergy.

Value of sialendoscopy-assisted transoral sublingual gland resection for a plunging ranula: case report and review.

OBJECTIVE: To highlight the value of sialendoscopy during transoral resection of the sublingual gland for a plunging ranula to prevent iatrogenic injury to the submandibular duct. METHOD AND RESULTS: The clinical course of a 20-year-old male with a plunging ranula was analysed. The patient underwent transoral resection of the affected sublingual gland and pseudocyst. Sialendoscopy was used to confirm patency of the submandibular duct with placement of a Marchal dilator to aid in preservation of the duct during sublingual gland dissection. The sublingual gland was successfully removed, with no injury to the submandibular duct or lingual nerve. During follow up, the patient had slight numbness to the tip of the tongue, which resolved after 2-3 days. Post-operative examination showed the submandibular duct to be intact and there was no swelling of the submandibular area. CONCLUSION: Sialendoscopy-assisted transoral sublingual gland resection for a plunging ranula is a safe and effective technique. Sialendoscopy aids in skeletonisation and preservation of the submandibular duct.

Neutron Laue and X-ray diffraction study of a new crystallographic superspace phase in n-nonadecane-urea.

Aperiodic composite crystals present long-range order without translational symmetry. These materials may be described as the intersection in three dimensions of a crystal which is periodic in a higher-dimensional space. In such materials, symmetry breaking must be described as structural changes within these crystallographic superspaces. The increase in the number of superspace groups with the increase in the dimension of the superspace allows many more structural solutions. This is illustrated in n-nonadecane-urea, revealing a fifth higher-dimensional phase at low temperature.

Relationship between increased cyclic AMP-phosphodiesterase activity and abnormal adenylyl cyclase regulation in leukocytes from patients with atopic dermatitis.

Atopic dermatitis (AD) is characterized by a variety of abnormal physiologic and pharmacologic responses in the skin. Leukocyte abnormalities of the cyclic nucleotide system include increased cAMP phosphodiesterase (PDE) and adenylyl cyclase activities. We have evaluated the possibility that a defect of the inhibitory GTP-binding protein (Gi) might cause inadequate modulation of adenylyl cyclase activity in AD leukocytes. We carried out a series of studies assessing adenylyl cyclase and Gi subunits in monocyte membranes. Using both pertussis toxin ribosylation and direct monoclonal antibody labeling of Gi proteins, we have shown evidence for a decrease or possible absence of one of the Gi proteins in atopic monocyte membranes. A genetic defect or toxin-mediated abnormality in leukocyte membrane Gi could account for these findings. Increased cAMP degradation by PDE may be a compensatory mechanism for increased cAMP synthesis that is regulated by GTP-binding proteins. But this increased PDE activity also rendered AD leukocytes hypo-responsive to immunofunction regulatory signals mediated by cAMP.

Progressive encephalomyelopathy and cerebellar degeneration in 10 captive-bred cheetahs.

Progressive ataxia, with head tremor, developed in 10 captive-born cheetah cubs under six months of age. The condition was usually preceded by coryza and an ocular discharge. Initially the ataxia and weakness affected the hindquarters, then the forelegs, and head tremor developed later. Significant pathological changes were confined to the central nervous system. There was widespread Wallerian degeneration in the funiculi of the spinal cord (except those in the dorsal columns), in the medulla and in the cerebellum. In the cerebellum there was degeneration of Purkinje cells and of the molecular and granular cell layers. There was chromatolysis in the Purkinje cells, the ventral horn cells of the spinal cord and in the neurons of the lateral vestibular nucleus. The olivary nucleus was necrotic. There were foci of inflammatory cells in the molecular layer of the cerebellum and in the medulla. The cause of the disease remains unknown.

[Risk of serious acute asthma due to lupine flour associated with peanut allergy]. / Le risque d'asthme aigu grave à la farine de lupin associé à l'allergie à l'arachide.

UNLABELLED: Lupine flour (lupinus albus), recently authorized in France in human food, cross-reacts with peanuts. We report a case of acute asthma in a patient with allergy to peanuts. EXEGESIS: This patient has a severe allergy to peanuts, presenting as acute asthma. Skin prick-tests to raw and cooked lupine flour were positive. The level of specific-IgE (Allerbio, France) to lupine flour were high. Oral challenge test induced acute asthma at a dose of 965 mg of lupine flour. This quantity may be included in 100 g of bread. CONCLUSION: This case report points out the fact that lupine flour is a high-risk allergen in patients presenting allergy to peanuts. It is necessary to evaluate the allergenic risk of new foods before their introduction into human daily food intake and to establish a network of allergy vigilance.

[Allergens]. / Les allergenes.

The clinical signs linked with immediate hypersensitivity, correspond with an abnormal reactivity of the immune system, which appears following contact with external substances, the allergens. Over the last few years there has been considerable progress in research on these substances in the domain of structural characterisation, biochemistry and immunological properties. Besides the definition of the word allergen linked to its immunological characteristics, our usual language maintains a certain ambiguity in its use which may characterise different states, including successive steps of the manufacture of an allergen extract. In effect the word allergen may designate the agent that is responsible for the allergic disease, for example cat, but also the raw material used for the manufacture of the corresponding extract, whether it be hair or squames; it may also apply to the final allergenic extract, the extract of cat hair or squames, as well as a precise molecule such as the major allergen of cat Fel d1 in the same example. After having reviewed several definitions as well as the nomenclature we will study the general characteristics of pneumoallergens and trophallergens, those of recombinant allergens, then the parameters of manufacture of allergen extracts.

[Allergenicity of lupin flour]. / Allergénicité de la farine de lupin.

Lupin flour is used in human food for its high quality nutritional and functional qualities. The frequency of crossed allergy between lupin flour and peanuts, both members of the family of Leguminosae, is strong, since 68% of patients who are allergic to peanut have shown positive reactions to lupin flour when tested by TPO-DA. Cases of isolated allergy to lupin flour without pre-existence of peanut allergy as well as workplace asthma by inhalation are also rarely seen. The specific allergens of lupin and those that participate in crosses with peanut have been studied by SDS-PAGE and immunoblot. The diversity of allergens contained in different lupin flour has also been studied. Further, the detection of lupin flour in a "pizza" flour which induced a strong allergic reaction exposed its eventual implication as a masked allergen.

[Allergy to cypress pollen: preparation of a reference and standardization extract in vivo]. / Allergie au pollen de cypres: preparation d'un extrait de référence et standardisation in vivo.

Development of Cypress allergy frequency led to the standardization of commercial cypress extract used for diagnosis and immunotherapy. Previous in vitro studies on two cypress pollen species (Cupressus sempervirens and Cupressus arizonica) allowed us to produce an allergenic solution composed by a mixture of both extracts for in vivo standardization. Dilutions of this allergenic solution were tested by prick-test on 44 patients with clinical allergy to cypress pollen to define the dilution that corresponds to a 6 mm wheal conformed to the definition of 100 IR. The mixture of the two major species found in France is justified by the in vitro study results. Extracts revealed complementary allergenic composition: Cup sempervirens showed a wider diversity of allergens whereas Cup arizonica showed a higher content of the major 43 kDa allergen. Thus, according to in vivo analysis, we are able to produce a standardized extract of Cypress pollen expressed in IR.

[Allergenicity of wheat flour]. / Allergénicité de la farine de blé.

Food allergy to wheat flour is a pathology that is found less frequently than coeliac disease or respiratory allergy to flour; it seems however to be a constant argument. Our study used a panel of 28 patients diagnosed with food allergy to wheat flour. Our objective was to characterise the reactivity of type IgE and IgG antibodies of these patients with regard to the different classes of proteins of wheat flour so as to establish an antigenic profile of the allergens of wheat in the framework of food allergy to flour. Our results show the implication of different classes of wheat proteins and notably the major reserve proteins (gliadins and glutens) in food allergy.

[The multifood allergy syndrome]. / Le syndrome des allergies alimentaires multiples.

Multiple food intolerance in infants and young children is increasingly diagnosed. More than 40% of infants less than 1 y.o. could be affected. The syndrome is characterized by the seriousness of atopic dermatitis (SCORAD > 50), by enterocolitis or failure to thrive or various associations of symptoms that may change over time. The evolution is long-lasting. Common food allergens are milk, egg, soy, wheat, but other ones can be implicated. The diagnosis is established by standardized oral challenges. Multiple etiopathogenic factors are involved: atopy, gastro-enteritis induced intestinal hyperpermeability, precocity of food diversification, breast-feeding continued after the onset of symptoms. Amino-acid based formulas have changed the evolution.