Magnetically tuning microwave propagation parameters in ferrofluids.

The paper reports on the frequency (f) and static magnetic field (H) dependencies of the microwave propagation parameters, in the ranges 0.1-6 GHz and 0-90.7 kA/m, of a kerosene-based ferrofluid with magnetite particles, filtered in magnetic field gradient. In the investigated range, the sample exhibits ferromagnetic resonance phenomenon and Maxwell-Wagner dielectric relaxation. Unlike the usual way of studying the propagation of microwaves through different media, in this paper we have defined an overall reflection coefficient, Rw(f, H), of a material with thickness, w, deposited on a total reflective support, which takes into account both the attenuation of wave within the material and the reflection at the air-material interface. Based on the measured relative magnetic permeability, [Formula: see text], and relative dielectric permittivity, [Formula: see text], a comprehensive and meaningful set of microwave propagation parameters are determined. Apart from Rw(f, H), this set of parameters of ferrofluid includes the attenuation constant of the electromagnetic wave, [Formula: see text](f, H), the phase constant [Formula: see text](f, H), the real, n'(f, H), and imaginary, n"(f, H), components of the refractive index, the reflection coefficient at the interface air-material, R(f, H), and the quarter wavelength in material, [Formula: see text](f, H). Based on the theoretical considerations and characteristics of ferrofluid, simplified and practical formulas of the propagation parameters are given and also possible applications of the results are suggested (such as electromagnetic absorber, phase shifter, microwave lenses and vibration sensor). This connection between theory and experimental results offers an example for the preliminary design of microwave applications of ferrofluids and, by extension, for any material consisting of magnetic nanoparticles dispersed in a dielectric matrix.

Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency - molecular profiling and functional rescue.

Mutations in the N-methyl-D-aspartate receptor (NMDAR) gene GRIN2A cause epilepsy-aphasia syndrome (EAS), a spectrum of epileptic, cognitive and language disorders. Using bioinformatic and patient data we shortlisted 10 diverse missense mutations for characterisation. We used high-throughput calcium-flux assays and patch clamp recordings of transiently transfected HEK-293 cells for electrophysiological characterization, and Western blotting and confocal imaging to assay expression and surface trafficking. Mutations P79R, C231Y, G483R and M705V caused a significant reduction in glutamate and glycine agonist potency, whilst D731N was non-responsive. These mutants, along with E714K, also showed significantly decreased total protein levels and trafficking to the cell surface, whilst C436R was not trafficked at all. Crucially this reduced surface expression did not cause the reduced agonist response. We were able to rescue the phenotype of P79R, C231Y, G483R and M705V after treatment with a GluN2A-selective positive allosteric modulator. With our methodology we were not able to identify any functional deficits in mutations I814T, D933N and N976S located between the glutamate-binding domain and C-terminus. We show GRIN2A mutations affect the expression and function of the receptor in different ways. Careful molecular profiling of patients will be essential for future effective personalised treatment options.

Secondary prevention of osteoporotic fractures: evaluation of the Amiens University Hospital's fracture liaison service between January 2010 and December 2011.

SUMMARY: The main goal was to assess the performance of the fracture liaison service (FLS) at Amiens University Hospital for 2 years. Osteoporosis medication was prescribed in 182 patients and 67.4 % were still taking treatment 18 months later. Secondary prevention of osteoporotic fractures has improved since the creation of the FLS. INTRODUCTION: The main goal of the present study was to assess the performance and results of the FLS at Amiens University Hospital, France. METHODS: This was an observational, single-center, ambispective study. All patients admitted to Amiens University Hospital between January 2010 and December 2011 for a low-trauma fracture (vertebral and non-vertebral fractures) were identified by a FLS nurse. Patients willing to enter the study were assessed for their osteoporosis risk factors, daily calcium intake, bone mineral density (BMD) by DXA, and clinical chemistry parameters. When indicated, the patients received a prescription for osteoporosis medication. The participation rate, type of osteoporosis medications, initiation rate, and osteoporosis treatment persistence 12 and 18 months later were assessed. RESULTS: Of the 1,439 patients contacted, 872 were eligible for inclusion. A total of 335 patients (participation rate 38.4 %) were included in the study (mean age 63.3 years; 71.9 % female). All patients underwent BMD measurement, and more than 90 % of them were assessed for osteoporosis risk factors and daily calcium intake. Osteoporosis medication was prescribed in 182 (75.5 %) of the patients in whom it was indicated (n = 241). The main class of osteoporosis medications prescribed was bisphosphonates (83.5 %), and 74.1 and 67.4 % of treated patients were still taking treatment 12 and 18 months later, respectively. The main cause of treatment discontinuation was non-renewal of the prescription by the patient's general practitioner. CONCLUSION: Secondary prevention of osteoporotic fractures in Amiens University Hospital has improved since the creation of the FLS, with encouragingly high treatment initiation and persistence rates.

Alterations in bone mineral density and bone turnover markers in newly diagnosed adults with lymphoma receiving chemotherapy: a 1-year prospective pilot study.

BACKGROUND: Bone mineral density (BMD) loss is poorly defined in lymphoma patients. The aim of this study was to measure the extent of BMD loss in newly diagnosed lymphoma patients receiving chemotherapy. PATIENTS AND METHODS: This was a prospective, single-center study conducted in patients aged≥18 years with previously confirmed lymphoma treated by chemotherapy. Patients with low baseline BMD defined as Z/T-score less than or equal to -2.5 and/or history of osteoporotic fractures were excluded. BMD was measured at baseline before initiating chemotherapy and 1 year later. Predictive factors of BMD loss were investigated. RESULTS: Forty-one lymphoma patients (31 males and 10 females) receiving chemotherapy were enrolled. The median age at diagnosis was 59 (range: 19-86) years. Histological subtypes were predominantly diffuse large B-cell lymphoma (58%), mostly stage III-IV (54%). All patients received chemotherapy and 22% of patients received second-line treatment due to relapse or progressive disease. Thirty-two patients were evaluable at 1 year. The mean BMD changes were: -2.7%±3.9% for lumbar spine (P<0.001), -2.2%±7.6% for femoral neck (P<0.01) and -2.6%±4.5% for total hip (P<0.0001). In multivariate analysis, predictive factors of BMD loss at baseline were (i) at lumbar spine: female gender (P=0.01), higher lactate dehydrogenase level (P=0.04) and lower creatinine clearance (P=0.01); (ii) at total hip: lower albumin (P=0.01), higher corrected serum calcium (P<0.01), lower alkaline phosphatase (AP) (P<0.01) and autologous stem cell transplant (P=0.03); and (iii) at femoral neck: higher corrected serum calcium (P=0.02) and lower bone AP (P=0.01). CONCLUSION: Adult patients with known lymphoma receiving chemotherapy experienced significant BMD loss at 1 year.

A possible role of the junctional face protein JP-45 in modulating Ca2+ release in skeletal muscle.

We investigated the functional role of JP-45, a recently discovered protein of the junctional face membrane (JFM) of skeletal muscle. For this purpose, we expressed JP-45 C-terminally tagged with the fluorescent protein DsRed2 by nuclear microinjection in myotubes derived from the C2C12 skeletal muscle cell line and performed whole-cell voltage-clamp experiments. We recorded in parallel cell membrane currents and Ca(2+) signals using fura-2 during step depolarization. It was found that properties of the voltage-activated Ca(2+) current were not significantly changed in JP-45-DsRed2-expressing C2C12 myotubes whereas the amplitude of depolarization-induced Ca(2+) transient was decreased compared to control myotubes expressing only DsRed2. Converting Ca(2+) transients to Ca(2+) input flux using a model fit approach to quantify Ca(2+) removal, the change could be attributed to an alteration in voltage-activated Ca(2+) permeability rather than to altered removal properties or a lower Ca(2+) content of the sarcoplasmic reticulum (SR). Determining non-linear capacitive currents revealed a reduction of Ca(2+) permeability per voltage-sensor charge. The results may be explained by a modulatory effect of JP-45 related to its reported in vitro interaction with the dihydropyridine receptor and the SR Ca(2+) binding protein calsequestrin (CSQ).

Voltage-controlled Ca2+ release and entry flux in isolated adult muscle fibres of the mouse.

The voltage-activated fluxes of Ca(2+) from the sarcoplasmic reticulum (SR) and from the extracellular space were studied in skeletal muscle fibres of adult mice. Single fibres of the interosseus muscle were enzymatically isolated and voltage clamped using a two-electrode technique. The fibres were perfused from the current-passing micropipette with a solution containing 15 mm EGTA and 0.2 mm of either fura-2 or the faster, lower affinity indicator fura-FF. Electrical recordings in parallel with the fluorescence measurements allowed the estimation of intramembrane gating charge movements and transmembrane Ca(2+) inward current exhibiting half-maximal activation at -7.60 +/- 1.29 and 3.0 +/- 1.44 mV, respectively. The rate of Ca(2+) release from the SR was calculated after fitting the relaxation phases of fluorescence ratio signals with a kinetic model to quantify overall Ca(2+) removal. Results obtained with the two indicators were similar. Ca(2+) release was 2-3 orders of magnitude larger than the flux carried by the L-type Ca(2+) current. At maximal depolarization (+50 mV), release flux peaked at about 3 ms after the onset of the voltage pulse and then decayed in two distinct phases. The slower phase, most likely resulting from SR depletion, indicated a decrease in lumenal Ca(2+) content by about 80% within 100 ms. Unlike in frog fibres, the kinetics of the rapid phase of decay showed no dependence on the filling state of the SR and the results provide little evidence for a substantial increase of SR permeability on depletion. The approach described here promises insight into excitation-contraction coupling in future studies of genetically altered mice.

Voltage-activated calcium signals in myotubes loaded with high concentrations of EGTA.

In the present study we describe the analysis of optically recorded whole cell Ca(2+) transients elicited by depolarization in cultured skeletal myotubes. Myotubes were obtained from the mouse muscle-derived cell line C2C12 and from mouse satellite cells. The cells were voltage-clamped and perfused with an artificial intracellular solution containing 15 mM EGTA to ensure that the bulk of the Ca(2+) mobilized by depolarization is bound to this extrinsic buffer. The apparent on- and off-rate constants of EGTA and the dissociation rate constant of fura-2 in the cell were estimated by investigating the Ca(2+)-dependence of kinetic components of the fluorescence decay after repolarization. These parameters were used to calculate the time course of the total voltage-controlled flux of Ca(2+) to the myoplasmic space (Ca(2+) input flux). The validity of the procedure was confirmed by model simulations using artificial Ca(2+) input fluxes. Both C2C12 and primary-cultured myotubes showed a very similar phasic-tonic time course of the Ca(2+) input flux. In most measurements, the input flux was considerably larger and showed a different time course than the estimated Ca(2+) flux carried by the L-type Ca(2+) channels, indicating that it consists mainly of voltage-controlled Ca(2+) release from the sarcoplasmic reticulum. In cells with extremely small fluorescence transients, the calculated input fluxes matched the kinetic characteristics of the Ca(2+) inward current, indicating that Ca(2+) release was absent. These measurements served as a control for the fidelity of the fluorimetric flux analysis. The procedures promise a deeper insight into alterations of Ca(2+) release gating in studies employing myotube expression systems for mutant or chimeric protein components of excitation-contraction coupling.

Excitation-contraction coupling in skeletal muscle of a mouse lacking the dihydropyridine receptor subunit gamma1.

1. In skeletal muscle, dihydropyridine (DHP) receptors control both Ca(2+) entry (L-type current) and internal Ca(2+) release in a voltage-dependent manner. Here we investigated the question of whether elimination of the skeletal muscle-specific DHP receptor subunit gamma1 affects excitation-contraction (E-C) coupling. We studied intracellular Ca(2+) release and force production in muscle preparations of a mouse deficient in the gamma1 subunit (gamma-/-). 2. The rate of internal Ca(2+) release at large depolarization (+20 mV) was determined in voltage-clamped primary-cultured myotubes derived from satellite cells of adult mice by analysing fura-2 fluorescence signals and estimating the concentration of free and bound Ca(2+). On average, gamma-/- cells showed an increase in release of about one-third of the control value and no alterations in the time course. 3. Voltage of half-maximal activation (V(1/2)) and voltage sensitivity (k) were not significantly different in gamma-/- myotubes, either for internal Ca(2+) release activation or for the simultaneously measured L-type Ca(2+) conductance. The same was true for maximal Ca(2+) inward current and conductance. 4. Contractions evoked by electrical stimuli were recorded in isolated extensor digitorum longus (EDL; fast, glycolytic) and soleus (slow, oxidative) muscles under normal conditions and during fatigue induced by repetitive tetanic stimulation. Neither time course nor amplitudes of twitches and tetani nor force-frequency relations showed significant alterations in the gamma1-deficient muscles. 5. In conclusion, the overall results show that the gamma1 subunit is not essential for voltage-controlled Ca(2+) release and force production.

[The effect of light intensity and neostigmine on the electroretinogram of Drosophila melanogaster]. / Influenta intensitatii luminoase si a neostigminei asupra electroretinogramei la Drosophila melanogaster.

In this article is presented the influence upon the electroretinogram, of some external factors acting at different levels of the visual system in the fruit fly, Drosophila melanogaster. The experiments revealed the effects generated by the light intensity modification as well as by the injection of a neuropharmaceutic--the neostigmine. The increase of the light stimuli intensity induced the same change of the rate between the amplitudes of the main electroretinographic components as the neostigmine does. It was used the "flickering" excitation regime, utilizing a data acquisition system adapted to the principal experimental device.

Biological activity of maleic anhydride copolymers. I. Biocompatibility and antitumoural effects of maleic anhydride-vinyl acetate, maleic anhydride-methyl methacrylate and maleic anhydride-styrene copolymers.

A series of maleic anhydride (MA)-vinyl acetate (VA), MA-methyl methacrylate (MM), and MA-styrene (S) copolymers were prepared and characterized. On employing various amounts of initiator, maleic anhydride-vinyl acetate, methyl methacrylate, and styrene copolymers with molecular weights ranging between 18,000 and 200,000 have been obtained. The in vivo and in vitro tests performed on K562 cellular cultures (human chronic myeloid leukemia) have shown that, as a function of the molecular weight, the synthesized copolymers demonstrate a 50% in vitro cytotoxicity and an average tumour regression of maximum 68%.