59 research outputs found

    Targeting of calcitonin gene-related peptide action as a new strategy for migraine treatment

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    Migraine is a chronic, recurrent disorder, characterized by attacks of severe pain, affecting around 1% of adult population. Many studies suggest, that trigeminovascular system plays a key role in pathogenesis of migraine and other primary headaches. Calcitonin gene-related peptide (CGRP) is an endogenous substance, which is regarded a key mediator released from trigeminovascular system after stimulation of sensory nerve endings, responsible for dilatation of peripheral vessels and sensory transmission. CGRP is and extensively studied peptide as one of the most promising targets in migraine drug research. In the article we focus on the role of CGRP in the pathophysiology of migraine and present current data on CGRP antagonists and CGRP monoclonal antibodies

    Zróżnicowanie i elastyczność postępowania diagnostycznego na przykładzie diagnozy logopedycznej pacjentów oddziału neurologicznego Szpitala Czerniakowskiego sp. z o.o. w Warszawie

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    Tekst obrazuje zróżnicowanie i elastyczność logopedycznego postępowania diagnostycznego dostosowanego do specyficznych potrzeb osób badanych na oddziale neurologicznym. Autorki wykorzystują podejście eksperymentalno-kliniczne z użyciem opracowanych przez siebie narzędzi badawczych. Prezentują schemat postępowania diagnostycznego obejmującego: skrócony wywiad logopedyczny lub rozmowę z badanym, ocenę możliwości językowych (tworzenia i odbioru komunikatów słownych), wstępną ocenę możliwości realizacyjnych z użyciem materiału wyrazowego lub zdaniowego, ocenę sprawności niewerbalnej artykulatorów oraz ocenę funkcji prymarnych. Autorki uzasadniają przyjęty sposób wstępnej diagnozy logopedycznej. Podkreślają złożoność powiązań między sposobem funkcjonowania komunikacyjnego chorych a indywidualnymi uwarunkowaniami biopsychicznymi i warunkami środowiskowymi wpływającymi na przebieg procesu diagnozy

    Reverse phase high-performance liquid chromatography for quantification of hydroxymethylnitrofurazone in polymeric nanoparticles

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    Hidroximetilnitrofural (NFOH) é um novo composto que possui atividade leishmanicida e tripanomicida potencial. Um método apropriado foi desenvolvido e validado para a determinação de NFOH em nanopartículas de poli(n-butil cianoacrilato) (PBCA). A separação cromatográfica foi obtida usando uma coluna C18 (5 µm de tamanho de partícula, 4,6 mm de diâmetro e 150 mm de comprimento), mantida a 25 °C, fase móvel composta de água e acetonitrila 80:20 (v/v), fluxo de 1,2 mL min- 1 e detecção por UV a 265 nm. Investigaram-se os seguintes parâmetros de validação: seletividade, linearidade, exatidão, precisão e robustez (mudanças na temperatura de coluna, proporção da fase móvel e fluxo). O método mostrou-se específico, o pico de NFOH não apresentou interferência dos picos provenientes dos excipientes das nanopartículas e separado do principal produto de degradação (nitrofural). A linearidade foi obtida na faixa de 0,94-13,11 μg mL- 1 (r2=0,999). O método mostrou exatidão (recuperação de 100,7%, DPR de 0,4 %) e precisão (intra-dia e inter-dia, 9,98-9,99 μg mL- 1 e DPR 0,3% a 0,5%, respectivamente). A robustez provou que o método pode resistir às mudanças propostas. Aplicação do método otimizado revelou eficiência de encapsulação de 64,4% (n=3). Portanto, o método foi desenvolvido e validado com sucesso para a determinação da eficiência de encapsulação de nanopartículas de NFOH-PBCA.Hydroxymethylnitrofurazone (NFOH) is a new compound with potential leishmanicidal and trypanocidal activity. Despite its effectiveness, the formulators have to overcome its poor aqueous solubility. Recently, polymeric nano-scale drug delivery systems have proposed for the treatment of neglected diseases. As several studies have confirmed the advantages of such formulations, and this approach provides new analytical challenges, including the need to detect trace amounts of the drug. A suitable method was developed and validated for NFOH determination bound to poly (n-butylcyanoacrylate) (PBCA) nanoparticles. The chromatographic separation was achieved using a C18 column maintained at 25 ºC and an isocratic mobile phase consisting of water and acetonitrile: 80:20 (v/v) at a flow rate of 1.2 mL min-1 and UV-detection at 265 nm. Investigated validation parameters included selectivity, linearity, accuracy, precision and robustness (changes in column temperature, mobile phase composition and flow). The method was specific, the peak of NFOH had no interference with any nanoparticle excipients and no co-elution with main degradation product (nitrofurazone). Linearity was over the range of 0.94 13.11 μg mL-1 (r2=0.999). The method was accurate and precise, recovery of 100.7%, RSD of 0.4%; intra-day and inter-day RSD range 9.98-9.99 μg mL-1 and 0.3% to 0.5%, respectively. Robustness confirmed that method could resist the applied changes. Application of the optimized method revealed an encapsulation efficiency of 64.4% (n=3). Therefore, the method was successfully developed and validated for the determination of the encapsulation efficiency of NFOH-PBCA nanoparticles

    Orai3 TM3 point mutation G158C alters kinetics of 2-APB–induced gating by disulfide bridge formation with TM2 C101

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    After endoplasmic reticulum (ER) Ca(2+) store depletion, Orai channels in the plasma membrane (PM) are activated directly by ER-resident STIM proteins to form the Ca(2+)-selective Ca(2+) release–activated Ca(2+) (CRAC) channel. However, in the absence of Ca(2+) store depletion and STIM interaction, the mammalian homologue Orai3 can be activated by 2-aminoethyl diphenylborinate (2-APB), resulting in a nonselective cation conductance characterized by biphasic inward and outward rectification. Here, we use site-directed mutagenesis and patch-clamp analysis to better understand the mechanism by which 2-APB activates Orai3. We find that point mutation of glycine 158 in the third transmembrane (TM) segment to cysteine, but not alanine, slows the kinetics of 2-APB activation and prevents complete channel closure upon 2-APB washout. The “slow” phenotype exhibited by Orai3 mutant G158C reveals distinct open states, characterized by variable reversal potentials. The slow phenotype can be reversed by application of the reducing reagent bis(2-mercaptoethylsulfone) (BMS), but in a state-dependent manner, only during 2-APB activation. Moreover, the double mutant C101G/G158C, in which an endogenous TM2 cysteine is changed to glycine, does not exhibit altered kinetics of 2-APB activation. We suggest that a disulfide bridge, formed between the introduced cysteine at TM3 position 158 and the endogenous cysteine at TM2 position 101, hinders transitions between Orai3 open and closed states. Our data provide functional confirmation of the proximity of these two residues and suggest a location within the Orai3 protein that is sensitive to the actions of 2-APB

    First results from the L3+C experiment at CERN

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    The L3+C experiment combines the high-precision spectrometer of the L3 detector at LEP, CERN, with a small air shower array. The momenta of cosmic ray induced muons can be measured from 20 to 2000 GeV/c. During the 1999 data taking period 5 billion muon events were recorded in the spectrometer. From April until mid Summer 2000 an additional 3 billion muon events have been recorded as well as 25 million air shower events. Here the first results on the muon momentum spectrum and charge ratio will be presented

    International Consensus Document on Obstructive Sleep Apnea

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    El objetivo principal de este documento internacional de consenso sobre apnea obstructiva del sueno es proporcionar unas directrices que permitan a los profesionales sanitarios tomar las mejores decisiones en la asistencia de los pacientes adultos con esta enfermedad según un resumen crítico de la literatura más actualizada. El grupo de trabajo de expertos se ha constituido principalmente por 17 sociedades científicas y 56 especialistas con amplia representación geográfica (con la participación de 4 sociedades internacionales), además de un metodólogo experto y un documentalista del Centro Cochrane Iberoamer icano. El documento consta de un manuscrito principal, con las novedades más relevantes del DIC, y una serie de manuscritos online que recogen las búsquedas bibliográficas sistemáticas de cada uno de los apartados del DIC. Este documento no cubre la edad pediátrica ni el manejo del paciente en ventilación mecánica crónica no invasiva (que se publicarán en sendos documentos de consenso aparte)

    Diagnosis of myelodysplastic syndromes in Poland: Polish Adult Leukemia Group (PALG) 2021 recommendations

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    Myelodysplastic syndromes (MDS) are a heterogeneous group of neoplastic diseases of the hematopoietic cells manifested by ineffective hematopoiesis and a tendency to transform into acute myeloid leukemia. MDS should be considered in the differential diagnosis of cytopenia, especially in the elderly. This article presents the recommendations of MDS experts of the Polish Adult Leukemia Group (PALG) for the diagnosis of myelodysplastic syndromes. We present current classifications and prognostic indices, as well as diagnostic examinations recommended for MDS: cytological, histopathological, immunophenotypic, cytogenetic and molecular tests. The aim of the study is to implement up-to-date knowledge about myelodysplastic syndromes into routine clinical practice, from the diagnosis of cytopenia to the specific diagnosis and prognosis in MDS patients.  Myelodysplastic syndromes (MDS) are a heterogeneous group of neoplastic diseases of the hematopoietic cells manifested by ineffective hematopoiesis and a tendency to transform into acute myeloid leukemia. MDS should be considered in the differential diagnosis of cytopenia, especially in the elderly. This article presents the recommendations of MDS experts of the Polish Adult Leukemia Group (PALG) for the diagnosis of myelodysplastic syndromes. We present current classifications and prognostic indices, as well as diagnostic examinations recommended for MDS: cytological, histopathological, immunophenotypic, cytogenetic and molecular tests. The aim of the study is to implement up-to-date knowledge about myelodysplastic syndromes into routine clinical practice, from the diagnosis of cytopenia to the specific diagnosis and prognosis in MDS patients.

    The European TeleCheck-AF project on remote app-based management of atrial fibrillation during the COVID-19 pandemic: Centre and patient experiences

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    Aims: TeleCheck-AF is a multicentre international project initiated to maintain care delivery for patients with atrial fibrillation (AF) during COVID-19 through teleconsultations supported by an on-demand photoplethysmography-based heart rate and rhythm monitoring app (FibriCheck® ). We describe the characteristics, inclusion rates and experiences from participating centres according the TeleCheck-AF infrastructure as well as characteristics and experiences from recruited patients.Methods: Three surveys exploring centre characteristics (n=25), centre experiences (n=23) and patient experiences (n=826) were completed. Self-reported patient characteristics were obtained from the app.Results: Most centres were academic (64%) and specialized public cardiology/district hospitals (36%). Majority of centres had AF outpatient clinics (64%) and only 36% had AF ablation clinics. The time required to start patient inclusion and total number of included patients in the project was comparable for centres experienced (56%) or inexperienced in mHealth use. Within 28 weeks, 1930 AF patients were recruited, mainly for remote AF control (31% of patients) and AF ablation follow-up (42%). Average inclusion rate was highest during the lockdown restrictions and reached a steady state at a lower level after easing the restrictions (188 vs 52 weekly recruited patients). Majority (>80%) of the centres reported no problems during the implementation of the TeleCheck-AF approach. Recruited patients (median age 64 [55-71], 62% male) agreed that the FibriCheck® app was easy to use (94%).Conclusions: Despite different health care settings and mHealth experiences, the TeleCheck-AF approach could be set up within an extremely short time and easily used in different European centres during COVID-19

    The 13th Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-IV Survey Mapping Nearby Galaxies at Apache Point Observatory

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    The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) began observations in July 2014. It pursues three core programs: APOGEE-2,MaNGA, and eBOSS. In addition, eBOSS contains two major subprograms: TDSS and SPIDERS. This paper describes the first data release from SDSS-IV, Data Release 13 (DR13), which contains new data, reanalysis of existing data sets and, like all SDSS data releases, is inclusive of previously released data. DR13 makes publicly available 1390 spatially resolved integral field unit observations of nearby galaxies from MaNGA,the first data released from this survey. It includes new observations from eBOSS, completing SEQUELS. In addition to targeting galaxies and quasars, SEQUELS also targeted variability-selected objects from TDSS and X-ray selected objects from SPIDERS. DR13 includes new reductions ofthe SDSS-III BOSS data, improving the spectrophotometric calibration and redshift classification. DR13 releases new reductions of the APOGEE-1data from SDSS-III, with abundances of elements not previously included and improved stellar parameters for dwarf stars and cooler stars. For the SDSS imaging data, DR13 provides new, more robust and precise photometric calibrations. Several value-added catalogs are being released in tandem with DR13, in particular target catalogs relevant for eBOSS, TDSS, and SPIDERS, and an updated red-clump catalog for APOGEE.This paper describes the location and format of the data now publicly available, as well as providing references to the important technical papers that describe the targeting, observing, and data reduction. The SDSS website, http://www.sdss.org, provides links to the data, tutorials and examples of data access, and extensive documentation of the reduction and analysis procedures. DR13 is the first of a scheduled set that will contain new data and analyses from the planned ~6-year operations of SDSS-IV.PostprintPeer reviewe
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