Comparative pharmacology of flatworm and roundworm glutamate-gated chloride channels: Implications for potential anthelmintics

Pharmacological targeting of glutamate-gated chloride channels (GluCls) is a potent anthelmintic strategy, evidenced by macrocyclic lactones that eliminate numerous roundworm infections by activating roundworm GluCls. Given the recent identification of flatworm GluCls and the urgent need for drugs against schistosomiasis, flatworm GluCls should be evaluated as potential anthelmintic targets. This study sought to identify agonists or modulators of one such GluCl, SmGluCl-2 from the parasitic flatworm Schistosoma mansoni. The effects of nine glutamate-like compounds and three monoterpenoid ion channel modulators were measured by electrophysiology at SmGluCl-2 recombinantly expressed in Xenopus laevis oocytes. For comparison with an established anthelmintic target, experiments were also performed on the AVR-14B GluCl from the parasitic roundworm Haemonchus contortus. L-Glutamate was the most potent agonist at both GluCls, but L-2-aminoadipate, D-glutamate and D-2-aminoadipate activated SmGluCl-2 (EC50 1.0 ± 0.1 mM, 2.4 ± 0.4 mM, 3.6 ± 0.7 mM, respectively) more potently than AVR-14B. Quisqualate activated only SmGluCl-2 whereas L-aspartate activated only AVR-14B GluCls. Regarding the monoterpenoids, both GluCls were inhibited by propofol, thymol and menthol, SmGluCl-2 most potently by thymol (IC50 484 ± 85 lM) and least potently by menthol (IC50 > 3 mM). Computational docking suggested that agonist and inhibitor potency is attributable to particular interactions with extracellular or membrane-spanning amino acid residues. These results reveal that flatworm GluCls are pharmacologically susceptible to numerous agonists and modulators and indicate that changes to the glutamate c-carboxyl or to the propofol 6-isopropyl group can alter the differential pharmacology at flatworm and roundworm GluCls. This should inform the development of more potent compounds and in turn lead to novel anthelmintics

Recombination of H3+ Ions in the Afterglow of a He-Ar-H2 Plasma

Recombination of H3+ with electrons was studied in a low temperature plasma in helium. The plasma recombination rate is driven by two body, H3+ + e, and three-body, H3+ + e + He, processes with the rate coefficients 7.5x10^{-8}cm3/s and 2.8x10^{-25}cm6/s correspondingly at 260K. The two-body rate coefficient is in excellent agreement with results from storage ring experiments and theoretical calculations. We suggest that the three-body recombination involves formation of highly excited Rydberg neutral H3 followed by an l- or m- changing collision with He. Plasma electron spectroscopy indicates the presence of H3.Comment: 4 figure

Пористая структура продуктов электрохимического синтеза на переменном токе нанодисперсных оксидов олова

Методами электронной микроскопии и низкотемпературной адсорбции азота изучена пористая структура продуктов электролиза металлического олова на переменном токе промышленной частоты. Установлено, что продукты синтеза характеризуются высокими значениями удельной площади поверхности и мезапористой структурой. Показано, что средний размер частиц варьирует в интервале 10…30 нм

Normative data on the Bonn Risk Index for calcium oxalate crystallization in healthy children

Bonn Risk Index (BRI) is being used for the assessment of urinary calcium oxalate (CaOx) crystallization. There are no published data regarding BRI during growth. The objective of this study was to establish age- and sex-dependent BRI values in healthy children and adolescents. A total of 1,050 Caucasian subjects aged 3–18 years (525 males, 525 females) without a history of kidney stone disease were enrolled in the cross-sectional study. The study group was divided into 15 ranges according to age, each comprising 70 subjects. Urinary ionized calcium [Ca(2+)] was measured using a selective electrode while the onset of spontaneous crystallization was determined using a photometer and titrating with 40 mmol/L ammonium oxalate (Ox(2−)). The calculation of BRI value was based on the ratio of [Ca(2+)] to the required amount of ammonium oxalate added to 200 ml of urine to induce crystallization. The median BRI was 0.26 1/L and the values of the 5th and 95th percentiles were 0.06 1/L and 1.93 1/L, respectively. BRI correlated positively with body-area-related BRI (1/L × 1.73 m(2)) (R = 0.18; P < 0.05), whereas a negative correlation was found between BRI and body weight (1/L × kg) (R = −0.85; P < 0.05). Neither sex nor age differences were detected in BRI across studied children and adolescents. The values of Bonn Risk Index were constant during growth and there was a limited influence of age and sex on BRI in children over 3 years of age. The BRI may be valuable in the evaluation of pediatric patients at risk for kidney stones, particularly if the BRI from stone formers is demonstrated to be higher than in normal children

Phonon structure in I-V characteristic of MgB2_{2} point-contacts

The search of the phonon structure at the above-gap energies was carried out for $d^{2}V/dI^{2}(V)$ spectra of MgB$_{2}$ point contacts with a normal metal. The two-band model is assumed not only for the gap structure in $dV/dI(V)$-characteristics, but also for phonons in $d^{2}V/dI^{2}(V)$ point-contact spectra, with up to the maximum lattice vibration energy. Since the current is carried mostly by charges of 3D-band, whereas the strong electron-phonon interaction occurs in 2D-band, we observe the phonon peculiarities due to ''proximity'' effect in {\it k}-space, which depends on the variation of interband coupling through the elastic scattering.Comment: 6 pages, 4 figures, revtex4, reported in International Conference "Modern Problems in Superconductivity", 9-13 September, Yalta, Ukrain

Cell surface antigens in renal tumour cells: detection by immunoluminescence and enzymatic analysis

Two renal cell carcinoma cell lines (49RC 43STR and 75RC 2STR) were characterized by detection of the cell surface proteins: CD44(var), intercellular adhesion molecule-1 (ICAM-1), urokinase-type plasminogen activator (uPA) and its receptor and aminopeptidase N (APN). To detect their localization the immunoluminescent technique was used. In addition, the enzyme activity of uPA and APN was investigated in cell suspensions as well as in monolayers. The latter procedure was more advantageous since the additional use of HPLC permits a single registration of the fluorescent hydrolysis-product AMC (7-amino-4-methylcoumarin) without interference by cellular autofluorescence or non-reacted fluorescent substrate. Unlike 75RC 2STR, the cell line 49RC 43STR expressed high levels of uPA and APN. Contrary to that the cell line 75RC 2STR expressed high levels of ICAM-1 and CD44(v6), whereas 49RC 43STR showed a low level of ICAM-1 and no distinct light signal with anti-CD44(v6). The uPA activity was measured directly as well as indirectly (via plasmin) with the substrate Z-Gly-Gly-Arg-AMC. Both activator and plasmin activity were inhibited by D-Val-Phe-Lys-CMK and phenylmethylsulfonyl fluoride. The anti-catalytic antibody to uPA and that to uPA receptor were found to be inhibiting the uPA activity in a concentration-dependent manner. APN activity was assayed using alanine-p-nitroanilide. Peptidase activity was effectively inhibited by 1,10-phenanthroline and partly inhibited by ethylenediamine-tetraacetic acid. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Specific heat of MgB2_2 in a one- and a two-band model from first-principles calculations

The heat capacity anomaly at the transition to superconductivity of the layered superconductor MgB$_2$ is compared to first-principles calculations with the Coulomb repulsion, $\mu^\ast$, as the only parameter which is fixed to give the measured $T_c$. We solve the Eliashberg equations for both an isotropic one-band and a two-band model with different superconducting gaps on the $\pi$ and $\sigma$ Fermi surfaces. The agreement with experiments is considerably better for the two-band model than for the one-band model.Comment: final published versio

Inhalation characteristics of asthma patients, COPD patients and healthy volunteers with the Spiromax® and Turbuhaler® devices: a randomised, cross-over study.

BACKGROUND: Spiromax® is a novel dry-powder inhaler containing formulations of budesonide plus formoterol (BF). The device is intended to provide dose equivalence with enhanced user-friendliness compared to BF Turbuhaler® in asthma and chronic obstructive pulmonary disease (COPD). The present study was performed to compare inhalation parameters with empty versions of the two devices, and to investigate the effects of enhanced training designed to encourage faster inhalation. METHODS: This randomised, open-label, cross-over study included children with asthma (n = 23), adolescents with asthma (n = 27), adults with asthma (n = 50), adults with COPD (n = 50) and healthy adult volunteers (n = 50). Inhalation manoeuvres were recorded with each device after training with the patient information leaflet (PIL) and after enhanced training using an In-Check Dial device. RESULTS: After PIL training, peak inspiratory flow (PIF), maximum change in pressure (∆P) and the inhalation volume (IV) were significantly higher with Spiromax than with the Turbuhaler device (p values were at least &lt;0.05 in all patient groups). After enhanced training, numerically or significantly higher values for PIF, ∆P, IV and acceleration remained with Spiromax versus Turbuhaler, except for ∆P in COPD patients. After PIL training, one adult asthma patient and one COPD patient inhaled &lt;30 L/min through the Spiromax compared to one adult asthma patient and five COPD patients with the Turbuhaler. All patients achieved PIF values of at least 30 L/min after enhanced training. CONCLUSIONS: The two inhalers have similar resistance so inhalation flows and pressure changes would be expected to be similar. The higher flow-related values noted for Spiromax versus Turbuhaler after PIL training suggest that Spiromax might have human factor advantages in real-world use. After enhanced training, the flow-related differences between devices persisted; increased flow rates were achieved with both devices, and all patients achieved the minimal flow required for adequate drug delivery. Enhanced training could be useful, especially in COPD patients

Phenomenological theory of the 3 Kelvin phase in Sr2RuO4

We model the 3K-phase of Sr2RuO4 with Ru-metal inclusion as interface state with locally enhanced transition temperatures. The resulting 3K-phase must have a different pairing symmetry than the bulk phase of Sr2RuO4, because the symmetry at the interface is lower than in the bulk. It is invariant under time reversal and a second transition, in general, above the onset of bulk superconductivity is expected where time reversal symmetry is broken. The nucleation of the 3K-phase exhibits a ``capillary effect'' which can lead to frustration phenomena for the superconducting states on different Ru-inclusions. Furthermore, the phase structure of the pair wave function gives rise to zero-energy quasiparticle states which would be visible in quasiparticle tunneling spectra. Additional characteristic properties are associated with the upper critical field Hc2. The 3K-phase has a weaker anisotropy of Hc2 between the inplane and z-axis orientation than the bulk superconducting phase. This is connected with the more isotropic nature Ru-metal which yields a stronger orbital depairing effect for the inplane magnetic field than in the strongly layered Sr$_2RuO4. An anomalous temperature dependence for the z-axis critical field is found due to the coupling of the magnetic field to the order parameter texture at the interface. Various other experiments are discussed and new measurements are suggested.Comment: 10 pages, 5 figure

A zone melting device for the in situ observation of directional solidification using high-energy synchrotron x rays editors-pick

Directional solidification (DS) is an established manufacturing process to produce high-performance components from metallic materials with optimized properties. Materials for demanding high-temperature applications, for instance in the energy generation and aircraft engine technology, can only be successfully produced using methods such as directional solidification. It has been applied on an industrial scale for a considerable amount of time, but advancing this method beyond the current applications is still challenging and almost exclusively limited to post-process characterization of the developed microstructures. For a knowledge-based advancement and a contribution to material innovation, in situ studies of the DS process are crucial using realistic sample sizes to ensure scalability of the results to industrial sizes. Therefore, a specially designed Flexible Directional Solidification (FlexiDS) device was developed for use at the P07 High Energy Materials Science beamline at PETRA III (Deutsches Elektronen–Synchrotron, Hamburg, Germany). In general, the process conditions of the crucible-free, inductively heated FlexiDS device can be varied from 6 mm/h to 12 000 mm/h (vertical withdrawal rate) and from 0 rpm to 35 rpm (axial sample rotation). Moreover, different atmospheres such as Ar, N2, and vacuum can be used during operation. The device is designed for maximum operation temperatures of 2200 °C. This unique device allows in situ examination of the directional solidification process and subsequent solid-state reactions by x-ray diffraction in the transmission mode. Within this project, different structural intermetallic alloys with liquidus temperatures up to 2000 °C were studied in terms of liquid–solid regions, transformations, and decompositions, with varying process conditions