Ex vivo effects of bisphenol A or zearalenone on the prepubertal rat testis.

Bisphenol A (BPA) and zearalenone (ZEA) are two widespread xenoestrogens involved in male reproductive disorders. Few studies investigated the effects of these compounds on the prepubertal testis, which is highly sensitive to endocrine disruptors such as xenoestrogens. An ex vivo approach was performed to evaluate the effects of BPA or ZEA (10-11, 10-9, 10-6 M) on the testes of 20 and 25 dpp rats. To investigate the involvement of classical nuclear ER-mediated estrogen signaling in these effects, pre-incubation with an antagonist (ICI 182.780 10-6 M) was performed. BPA and ZEA have similar effects on spermatogenesis- and steroidogenesis-related endpoints in the immature testis, but our study highlights different age-dependent patterns of sensitivity to each compound during the prepubertal period. Moreover, our results indicate that the effects of BPA are likely to be induced by nuclear ER, whereas those of ZEA appear to involve other mechanisms.

Monitoring of sterigmatocystin biosynthesis using RT-qPCR in airborne Aspergillus species of the series Versicolores.

Aspergilli series Versicolores have been shown to be explanatory variables for different symptoms like coughing and dizziness experienced by residents of mold-damaged homes. Among these species, eight are particularly recurrent in bioaerosols: Aspergillus amoenus, A. creber, A. fructus, A. jensenii, A. protuberus, A. puulaauensis, A. sydowii and A. tabacinus. In order to monitor the biosynthesis of sterigmatocystin (a mycotoxin associated with a risk of cancer development) and the development of these molds, we developed an RT-qPCR tool by targeting the aflR and rho1 genes. A total of 30 fungal isolates representing these eight species were included. For each of them, sterigmatocystin was quantified by UPLC-HRMS and (1 â†’ 3)-ß-D-glucan by visible spectrophotometry using Endosafe®-PTS™-Glucan Cartridges. After validation of our method by RT-qPCR, the direct assay was compared to the amount of aflR and rho1 cDNA. The sterigmatocystin and aflR assays showed a significant correlation between these two approaches (p < 0.0001), demonstrated for the first time the production of sterigmatocystin by A. tabacinus and suggested the ability of A. sydowii to synthesize sterigmatocystin. Assays conducted on (1 â†’ 3)-ß-D-glucan and rho1 did not show a correlation, supporting the multiplicity of functions performed in fungal cells by the RHO1 GTPase. The proposed tool could allow monitoring of sterigmatocystin biosynthesis by Aspergillus of the series Versicolores under different culture and climatic conditions.

Deoxynivalenol enhances estrogen receptor alpha-induced signaling by ligand-independent transactivation.

Deoxynivalenol (DON), which is one of the prevalent mycotoxins in food and feeds, exerts adverse effects on animal and human health. These effects are mainly associated with its ribotoxic properties, although few studies suggest the involvement of other mechanisms of action. To assess the ability of DON to disrupt estrogen signaling, we conducted an in vitro study using MCF-7 and MDA-MB-231 cells. After 72h, DON reduced cell viability in both cell lines, thus highlighting its well-known cytotoxic effect. However, after 6h, DON increased the expression of estrogen-responsive genes, hence demonstrating the stimulation of estrogen signaling by this mycotoxin after a short-term exposure. This effect was partially reversed by siRNA-mediated silencing of ERα expression and by 4-hydroxytamoxifen (ERα antagonist), but neither by G36 (GPER antagonist) nor by the siRNA-mediated silencing of PPARγ2 expression. Moreover, DON exposure induced an increase in the level of ERα phosphorylation at serine 167. Furthermore, when combined with zearalenone (a naturally co-occurring mycotoxin recognized as an endocrine disruptor), DON increased the expression of estrogen-responsive genes to a greater extent than each individual compound taken separately. Taken together, our results suggest, for the first time, that DON can disrupt estrogen signaling through the ligand-independent activation of ERα.

[Diagnosis of an increased serum level of ferritin]. / Démarche diagnostique devant une hyperferritinémie.

The discovery of a hyperferritinemia is most of the time fortuitous. The diagnostic approach aims at looking for the responsible etiology and at verifying if an iron hepatic overload is present or not. Three diagnostic steps are proposed. The clinical elements and a few straightforward biological tests are sufficient at first to identify one of the four main causes: alcoholism, inflammatory syndrome, cytolysis, and metabolic syndrome. None of these causes is associated with a significant iron hepatic overload. If the transferring saturation coefficient is raised (>50%) a hereditary hemochromatosis should be discussed. Secondly, less common disorders will be discussed. Among these, only the chronic hematological disorders either acquired or congenital are at risk of iron hepatic overload. Thirdly, if a doubt persists in the etiologic research, and the serum ferritin level is very high or continues to rise, it is essential to verify that there is no iron hepatic overload. For that purpose, the MRI with study of the iron overload is the main test, which will guide the therapeutic attitude. Identification of more than a single etiology occurs in more than 40% of the cases.

Multidimensional analysis of clinical symptoms in patients with Fabry's disease.

AIM: Fabry's disease is an X-linked inherited lysosomal storage disorder caused by the deficient activity of alpha-galactosidase A. The interrelationships between clinical symptoms in Fabry patients have not yet been fully established. Using cluster and multivariate analysis, the aim of the study was to determine the relationships among clinical symptoms and organ involvement, and predictive clinical symptoms for disease severity. METHODS: Clinical data obtained from 108 French Fabry patients were retrospectively collected and analysed using multiple correspondence analysis and hierachical ascendant classification. Multivariate analysis was also performed to determine among clinical symptoms predictors for cardiac disease (HRT), renal involvement (KDN) and brain complication (STR). RESULTS: The cohort comprised 41 male patients (aged 28.9 ± 11.6 years) and 67 female patients (aged 40.4 ± 15.5 years). Three main clusters of clinical symptoms could be delineated, characterising disease progression: the first cluster grouped digestive disorders (found in 30% of the patients) and exercise intolerance (32%), the second, cluster dyshidrosis (47%), acroparesthesia (67%), angiokeratoma (44%) and cornea verticillata (54%), the third, cluster grouped KDN (30%), HRT (39%) and STR (25%) and hearing loss (44%). In univariate analysis, the patient age predicted HRT and KDN, dyshidrosis predicted HRT and STR, angiokeratoma predicted KDN and cornea verticilla and hearing loss predicted KDN, HRT and STR. In multivariate analysis, hearing loss and age were independent predictors of organ complication. CONCLUSION: Among the various interrelated clinical symptoms occurring in Fabry disease, patients with dyshidrosis and particularly hearing disorders appear to be at higher risk of organ complications.

Thermal bistability-based method for real-time optimization of ultralow-threshold whispering gallery mode microlasers.

A method based on thermal bistability for ultralow-threshold microlaser optimization is demonstrated. When sweeping the pump laser frequency across a pump resonance, the dynamic thermal bistability slows down the power variation. The resulting line shape modification enables a real-time monitoring of the laser characteristic. We demonstrate this method for a functionalized microsphere exhibiting a submicrowatt laser threshold. This approach is confirmed by comparing the results with a step-by-step recording in quasi-static thermal conditions.

Fabry disease 'The New Great Imposter': results of the French Observatoire in Internal Medicine Departments (FIMeD).

Fabry disease (FD) is an X-linked lysosomal storage disorder due to α-galactosidase A deficiency. It is associated with a broad range of clinical symptoms, resulting in frequent misdiagnosis and diagnostic delay, which may impact on patient outcomes. This retrospective observational study of 58 FD patients referred to 10 internal medicine departments in France aimed to review differential diagnoses received prior to diagnosis and examines diagnostic delay. The average age at the time of diagnosis was 27.6 years (range: 10-60) and 42.2 years (range: 9-77) among the 23 males and 35 females analyzed, respectively. Most common symptoms that led to FD diagnosis were family history of FD (12 males and 27 females), followed by pain in extremities (10 males and 5 females), and angiokeratoma (8 males and 4 females). Eighteen patients had received alternative diagnoses prior to FD diagnosis, including a female patient with four previous diagnoses. Four case reports are presented, which illustrate the diagnostic 'odyssey' and delayed diagnosis often experienced by patients. Clinicians should consider a diagnosis of FD when presented with a wide range of symptoms, thus helping to shorten the diagnostic delay and facilitating early therapy with enzyme replacement therapy to improve patient outcomes.

Scalp vein thrombosis mimicking giant cell arteritis relapse.

Scalp vein thrombosis is an unusual complication during giant cell arteritis. Revealed by headache, it can be misdiagnosed as a disease relapse. An ultrasound scan should rapidly be performed to make the diagnosis, avoiding inappropriate treatment escalation.

[Treatment of immune thrombocytopenia: a retrospective study of 40 patients]. / Traitement du purpura thrombopénique immunologique : étude rétrospective de 40 patients.

PURPOSE: Immune thrombocytopenia (ITP) is an auto-immune disease associating a peripheral platelet destruction without increased central production. METHODS: Forty patients with chronic ITP were retrospectively analyzed for clinical and biological presentation and response to treatment. RESULTS: Mean age at diagnosis was 54 years. ITP was revealed by hemorrhage in 65 % of the patients. Despite very low platelet count, no life threatening hemorrhage was observed. Platelet associated antibodies were found in 66 %, usually directed against GPIIb/IIIa. Corticosteroids were used as first line treatment, with response in 54 %, and relapse in 86 %. A response was observed in 42.1 % with dapsone, which was well tolerated, a relapse occurring in 37.5 % of the patients. Rituximab (RTX) allowed a response rate of 42.1 %, prolonged in 40 % of the patients. A response was achieved in 42.9 % cases after splenectomy, without any relapse. No factor was identified to predict the response to treatment. CONCLUSION: ITP is a rare disorder occurring most frequently in middle aged patients. Because of high relapse or no response rates, many treatments should be used. Dapsone offers a good efficacy without major side effects. RTX is well tolerated and allows a good response rate. The use of new agents like thrombopoietin receptor agonist or new therapeutics against B lymphocytes should be defined.

Excitation mapping of whispering gallery modes in silica microcavities.

We report the direct observation of the electromagnetic-field distribution of whispering gallery modes in silica microcavities (spheres and toroids). It is revealed by their excitation efficiency with a tapered fiber coupler swept along the meridian. The originality of this method lies in the use of the coupler itself for the near-field mapping, eliminating the need of additional tools used in previous work. This method is successfully applied to microspheres and microtoroids.

Frequency tuning of the whispering-gallery modes of silica microspheres for cavity quantum electrodynamics and spectroscopy.

We have tuned the whispering-gallery modes of a fused-silica microresonator over nearly 1 nm at 800 nm, i.e., over half a free spectral range, or 10(6) linewidths of the resonator. This result has been achieved by use of a new method based on the stretching of a two-stem microsphere. We describe devices that will permit new cavity QED experiments with this high- Q optical resonator when it is desirable to optimize its coupling to emitters with given transition frequencies. The demonstrated tuning capability is compatible with both UHV and low-temperature operation, which should be useful for future experiments with laser-cooled atoms or single quantum dots.

Characterizing whispering-gallery modes in microspheres by direct observation of the optical standing-wave pattern in the near field.

We demonstrated the use of a near-field probe to map the evanescent field of an optical standing wave in a fused-silica whispering-gallery mode microresonator. The periodicity of the observed standing wave allows us to estimate accurately the radial mode number of the whispering-gallery mode resonance that is being excited. We find that the use of a fiber half-coupler to excite these resonances in fused-silica microspheres results in only the lowest radial mode numbers' being strongly excited, as predicted.

Mapping whispering-gallery modes in microspheres with a near-field probe.

We demonstrate the use of a near-field probe to map the angular dependence of high-Q whispering-gallery modes in fused-silica microspheres. The mapping is performed by placing a micrometer-sized tip formed on the end of a monomode fiber into the evanescent f ield at the microsphere surface, causing light to be coupled from the microsphere resonance into the fiber guided mode. The light output of the fiber is then measured while the tip is moved to different points on the microsphere surface. We have used this method to investigate the lifting of spherical degeneracy in the system.

Splitting of high-Q Mie modes induced by light backscattering in silica microspheres.

We have observed that very high-Q Mie resonances in silica microspheres are split into doublets. This splitting is attributed to internal backscattering that couples the two degenerate whispering-gallery modes propagating in opposite directions along the sphere equator. We have studied this doublet structure by high-resolution spectroscopy. Time-decay measurements have also been performed and show a beat note corresponding to the coupling rate between the clockwise and counterclockwise modes. A simple model of coupled oscillators describes our data well, and the backscattering efficiency that we measure is consistent with what is observed in optical fibers.

Burst-mode gain switched technique for high peak and average optical energy extraction.

The optical performance of a cw PIE CO(2) laser has been substantially improved through the adoption of a burst-mode gain switching technique. The approach has provided a doubling of the average beam power extractable from the device. With appropriate optimization, the process could possibly permit the attainment of pulsed energy extraction in the kilohertz range, and with average optical powers within the several tens of kilowatt category.

Annular-coupled concave-convex stable resonator for large-volume high-quality energy extraction.

A theoretical investigation of a stable concave-convex resonator configuration, which appears suitable for single-mode high-power energy extraction from large volume gain media, is presented. The design features annular output coupling with a surprisingly uniform near-field intensity distribution. The computer-based analysis, supported by preliminary experimental results, suggests that acceptable alignment tolerances are provided along with an unusually small beam divergence. With proper design, a far-field divergence of 0.5 mrad, encompassing near 80% of the total laser energy, appears feasible. Operational data, recently obtained with this optical extraction approach, have revealed a further important practical advantage over an unstable resonator, being far less prone to mode degradation and hot spot formation on optical component misalignment.