25,665 research outputs found
KCNQ/M currents in sensory neurons: Significance for pain therapy
No full textNeuronal hyperexcitability is a feature of epilepsy and both inflammatory and neuropathic pain. M currents [I-K(M)] play a key role in regulating neuronal excitability, and mutations in neuronal KCNQ2/3 subunits, the molecular correlates of I-K(M), have previously been linked to benign familial neonatal epilepsy. Here, we demonstrate that KCNQ/M channels are also present in nociceptive sensory systems. I-K(M) was identified, on the basis of biophysical and pharmacological properties, in cultured neurons isolated from dorsal root ganglia (DRGs) from 17-d-old rats. Currents were inhibited by the M-channel blockers linopirdine (IC50, 2.1 muM) and XE991 (IC50, 0.26 muM) and enhanced by retigabine (10 muM). The expression of neuronal KCNQ subunits in DRG neurons was confirmed using reverse transcription-PCR and single-cell PCR analysis and by immunofluorescence. Retigabine, applied to the dorsal spinal cord, inhibited C and Adelta fiber-mediated responses of dorsal horn neurons evoked by natural or electrical afferent stimulation and the progressive "windup" discharge with repetitive stimulation in normal rats and in rats subjected to spinal nerve ligation. Retigabine also inhibited responses to intrapaw application of carrageenan in a rat model of chronic pain; this was reversed by XE991. It is suggested that I-K(M) plays a key role in controlling the excitability of nociceptors and may represent a novel analgesic target
AMČR - projekt M-201300752
No full textStav: 6Podnět: TI 15 BJ Hrabová . Pod Hojgrovými, II. etapa - komunikace a IS
DNA and RNA flow cytometry in multiple myeloma: clinical correlations.
No full textFlow cytometric studies of cellular DNA and RNA content using the acridine-orange technique were conducted in 81 patients with multiple myeloma (MM). All patients were treated with the M-2 protocol and clinical response was evaluated according to the criteria of the Chronic Leukemia-Myeloma Task Force. Aneuploid DNA stemlines were found in 38.2% of untreated patients with a median DNA index (DNA-I) of 1.15 in marrow aspirates and 1.22 in biopsy specimens. The median percentage of cells with abnormal DNA content was 31.5 (aspirates) and 35 (biopsy specimens) and a positive correlation with the percentage of bone marrow plasma cells was observed. Significantly higher proliferation (S-phase) was found in marrow biopsy specimens as compared with marrow aspirates. Significantly higher RNA content (RNA index [RNA-I]) was observed in aneuploid versus diploid patients in biopsy material. There was no difference in response to the Memorial Hospital M-2 protocol between diploid and aneuploid patients. In patients with DNA-I greater than 1.15 remission duration was shorter as compared with DNA-I less than or equal to 1.15. Furthermore, no difference in cellular RNA content was noted between responders and nonresponders. This study demonstrates no correlation between cellular RNA content and response, as previously described for patients treated with vincristine, Adriamycin, and dexamethasone (VAD), but DNA aneuploidy appears to be an adverse prognostic factor in MM patients treated with the M-2 protocol. It also demonstrates that prognostic models for MM are not universal but depend on the chemotherapeutic regimen used
AMČR - projekt M-201900090
No full textStav: 6Podnět: Novostavba rodinného domu o 1.bj., vč. přípojek vody, kanalizace, NN, zpevněných ploch a retenční nádržeOznačení projektu: 2019_01 - Březolupy - R
Hydrogen transfer between ligands: A density functional study of the rearrangement of M(eta(6)-C7H8)(2) into M(eta(7)-C7H7)(eta(5)-C7H9) [M = Mo, Mo+, Zr]
No full textThe electronic structure of the family of sandwich complexes M(eta(6)-C7H8)(2) and M(eta(7)-C7H7)-(eta(5)-C7H9) (M = Mo, Mo+, Zr) was investigated using density functional theory, and their geometries were accounted for. The mechanism for conversion of M(eta(6)-(CH8)-H-7)(2) into M(eta(7)-C7H7)(eta(5)-C7H9) by hydrogen transfer was investigated, and the experimental trends were reproduced. The neutral Mo species was calculated to have an activation free energy 13 kJ mol(-1) lower than the cationic Mo+. The rate-limiting step for the transfer in the neutral molybdenum species is breaking of the C-H bond to form a molybdenum hydride intermediate, which rapidly converts into the rearranged product. The transition state is late on the reaction coordinate, and C-H bond breaking occurs after ring slippage to form an (eta(6), eta(4)) 16-electron species. The cationic molybdenum species has a similar reaction profile. The zirconium species is found to have two competing pathways both with higher activations energies: one with an (eta(7), eta(5)) Zr-H intermediate, the other occurring by direct transfer of the hydrogen without forming Zr-H species. The effect of adding PH3 to the zirconium system has also been studied, which has the effect of lowering the barrier to the direct transfer of hydrogen between the ligands
Tumour hypoxia imaging with [F-18]FAZA PET in head and neck cancer patients: a pilot study
No full textPurpose Hypoxia is an important negative prognostic factor for radiation treatment of head and neck cancer. This study was performed to evaluate the feasibility of use of F-18-labelled fluoroazomycin arabinoside ([F-18]FAZA) for clinical PET imaging of tumour hypoxia. Methods Eleven patients (age 59.6 +/- 9 years) with untreated advanced head and neck cancer were included. After injection of approximately 300 MBq of [F-18]FAZA, a dynamic sequence up to 60 min was acquired on an ECAT HR+ PET scanner. In addition, approximately 2 and 4 h p.i., static whole-body PET (n=5) or PET/CT (n=6) imaging was performed. PET data were reconstructed iteratively (OSEM) and fused with CT images (either an external CT or the CT of integrated PET/CT). Standardised uptake values (SUVs) and tumour-to-muscle (T/M) ratios were calculated in tumour and normal tissues. Also, the tumour volume displaying a T/M ratio > 1.5 was determined. Results Within the first 60 min of the dynamic sequence, the T/M ratio generally decreased, while generally increasing at later time points. At 2 h p.i., the tumour SUVmax and SUVmean were found to be 2.3 +/- 0.5 (range 1.5-3.4) and 1.4 +/- 0.3 (range 1.0-2.1), respectively. The mean T/M ratio at 2 h p.i. was 2.0 +/- 0.3 (range 1.6-2.4). The tumour volume displaying a T/M ratio above 1.5 was highly variable. At 2 h p.i., [F-18]FAZA organ distribution was determined as follows: kidney > gallbladder > liver > tumour > muscle > bone > brain > lung. Conclusion [F-18]FAZA PET imaging appears feasible in head and neck cancer patients, and the achieved image quality is adequate for clinical purposes. Based on our initial results, [F-18]FAZA warrants further evaluation as a hypoxia PET tracer for imaging of cancer
Constraining structure formation using EDGES
No full textThe experiment to detect the global epoch of reionization signature (EDGES) collaboration reported the detection of a line at 78 MHz in the sky-averaged spectrum due to neutral hydrogen (HI) 21-cm hyperfine absorption of cosmic microwave background (CMB) photons at redshift z similar to 17. This requires that the spin temperature of HI be coupled to the kinetic temperature of the gas at this redshift through the scattering of Lyman-alpha photons emitted by massive stars. To explain the experimental result, star formation needs to be sufficiently efficient at z similar to 17 and this can be used to constrain models in which small-scale structure formation is suppressed (DMF models), either due to dark matter free-streaming or non-standard inflationary dynamics. We combine simulations of structure formation with a simple recipe for star formation to investigate whether these models emit enough Lyman-alpha photons to reproduce the experimental signal for reasonable values of the star formation efficiency, f(*). We find that a thermal warm dark matter (WDM) model with mass m(WDM) 4.3 keV is consistent with the timing of the signal for f(*). less than or similar to 2%. The exponential growth of structure around z similar to 17 in such a model naturally generates a sharp onset of the absorption. A warmer model with 1 m(WDM) similar to 3 keV requires a higher star formation efficiency, f(*) similar to 6%, which is a factor of few above predictions of current star formation models and observations of satellites in the Milky Way. However, uncertainties in the process of star formation at these redshifts do not allow to derive strong constrains on such models using 21-cm absorption line. The onset of the 21-cm absorption is generally slower in DMF than observed in cold dark matter (CDM) models, unless some process significantly suppresses star formation in halos with masses below similar to 10(8) h(-1) M-circle dot
AMČR - projekt M-202501108
No full textStav: 6Podnět: Stavební úpravy a přístavba objektu č.p.593, Uherské Hradiště - SO 107 zpevněné plochy, venkovní úpravyOznačení projektu: 2025_03 - UH - Dvořákova - SO 107 zpevněné plochyOznačení stavby: MUUH-SŽP/33028/2023/Do/BJ 4
In a horizontal layer with free upper surface
No full textOn existence of non steady compressible viscous flows in a horizontal layer with free upper surface, in a small time interval. The proof adapt a Galerkin procedure
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