reactivity
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Advanced glycation accelerated by chronic hyperglycaemia contributes to the development of diabetic vascular complications throughout several mechanisms. One of these mechanisms is supposed to be impaired microvascular reactivity, that precedes significant vascular changes. The aim of this study was to find an association between advanced glycation, the soluble receptor for AGEs (sRAGE), and microvascular reactivity (MVR) in diabetes. Skin autofluorescence (SAF), which reflects advanced glycation, was assessed by AGE-Reader, MVR was measured by laser Doppler fluxmetry and evaluated together with sRAGE in 43 patients with diabetes (25 Type 1 and 18 Type 2) and 26 healthy controls of comparable age. SAF was significantly higher in patients with diabetes compared to controls (2.4 ± 0.5 vs. 2.0 ± 0.5 AU; p < 0.01). Patients with diabetes with SAF > 2.3 AU presented significantly worse MVR in both post-occlusive reactive hyperaemia (PORH) on the finger and forearm, and thermal hyperaemia (TH), compared to patients with SAF < 2.3 AU. SAF was age dependent in both diabetes (r = 0.41, p < 0.01) and controls (r = 0.45, p < 0.05). There was no association between SAF and diabetes control expressed by glycated haemoglobin. A significant relationship was observed between SAF and sRAGE in diabetes (r = 0.56, p < 0.001), but not in controls. A significant inverse association was found between SAF and MVR on the forearm in diabetes (PORH: r = -0.42, p < 0.01; TH: r = -0.46, p < 0.005). Both advanced glycation expressed by higher SAF or sRAGE and impaired MVR are involved in the pathogenesis of vascular complications in diabetes, and we confirm a strong interplay of these processes in this scenario.
- Klíčová slova
- AGEs, Diabetes mellitus, Microvascular reactivity, Skin autofluorescence, Soluble RAGE,
- MeSH
- diabetes mellitus * diagnóza MeSH
- diabetické angiopatie * diagnóza etiologie MeSH
- glykovaný hemoglobin analýza MeSH
- hyperemie * MeSH
- kůže chemie MeSH
- lidé MeSH
- produkty pokročilé glykace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- glykovaný hemoglobin MeSH
- produkty pokročilé glykace MeSH
Background: Chronic vagal nerve stimulation (VNS) is a well-established non-pharmacological treatment option for drug-resistant epilepsy. This study sought to develop a statistical model for prediction of VNS efficacy. We hypothesized that reactivity of the electroencephalogram (EEG) to external stimuli measured during routine preoperative evaluation differs between VNS responders and non-responders. Materials and Methods: Power spectral analyses were computed retrospectively on pre-operative EEG recordings from 60 epileptic patients with VNS. Thirty five responders and 25 non-responders were compared on the relative power values in four standard frequency bands and eight conditions of clinical assessment-eyes opening/closing, photic stimulation, and hyperventilation. Using logistic regression, groups of electrodes within anatomical areas identified as maximally discriminative by n leave-one-out iterations were used to classify patients. The reliability of the predictive model was verified with an independent data-set from 22 additional patients. Results: Power spectral analyses revealed significant differences in EEG reactivity between responders and non-responders; specifically, the dynamics of alpha and gamma activity strongly reflected VNS efficacy. Using individual EEG reactivity to develop and validate a predictive model, we discriminated between responders and non-responders with 86% accuracy, 83% sensitivity, and 90% specificity. Conclusion: We present a new statistical model with which EEG reactivity to external stimuli during routine presurgical evaluation can be seen as a promising avenue for the identification of patients with favorable VNS outcome. This novel method for the prediction of VNS efficacy might represent a breakthrough in the management of drug-resistant epilepsy, with wide-reaching medical and economic implications.
- Klíčová slova
- EEG reactivity, efficacy prediction, epilepsy, epilepsy treatment, neurostimulation, vagal nerve stimulation,
- Publikační typ
- časopisecké články MeSH
The formation and detailed spectroscopic characterization of the first biuret-containing monoanionic superoxido-NiII intermediate [LNiO2 ]- as the Li salt [2; L=MeN[C(=O)NAr)2 ; Ar=2,6-iPr2 C6 H3 )] is reported. It results from oxidation of the corresponding [Li(thf)3 ]2 [LNiII Br2 ] complex M with excess H2 O2 in the presence of Et3 N. The [LNiO2 ]- core of 2 shows an unprecedented nucleophilic reactivity in the oxidative deformylation of aldehydes, in stark contrast to the electrophilic character of the previously reported neutral Nacnac-containing superoxido-NiII complex 1, [L'NiO2 ] (L'=CH(CMeNAr)2 ). According to density-functional theory (DFT) calculations, the remarkably different behaviour of 1 versus 2 can be attributed to their different charges and a two-state reactivity, in which a doublet ground state and a nearby spin-polarized doublet excited-state both contribute in 1 but not in 2. The unexpected nucleophilicity of the superoxido-NiII core of 2 suggests that such a reactivity may also play a role in catalytic cycles of Ni-containing oxygenases and oxidases.
- Klíčová slova
- dioxygen ligands, nickel, structure elucidation, structure-activity relationships, two-state reactivity,
- MeSH
- komplexní sloučeniny chemie MeSH
- kvantová teorie MeSH
- kyslík chemie MeSH
- lithium chemie MeSH
- molekulární modely MeSH
- nikl chemie MeSH
- oxidace-redukce MeSH
- oxidoreduktasy chemie MeSH
- oxygenasy chemie MeSH
- soli chemie MeSH
- superoxidy chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- komplexní sloučeniny MeSH
- kyslík MeSH
- lithium MeSH
- nikl MeSH
- oxidoreduktasy MeSH
- oxygenasy MeSH
- soli MeSH
- superoxidy MeSH
It has been appreciated for more than three decades that the interactions between the T-cell antigen receptor and self-antigens are the major determinants of the cell fates of developing thymocytes and the establishment of central tolerance. However, recent evidence shows that the level of self-reactivity substantially contributes to fate choices of positively selected mature T cells in homeostasis, as well as during immune responses. This implies that individual clones of peripheral T cells are predisposed to specific functional properties based on the self-reactivity of their antigen receptors. Overall, the relative difference in the self-reactivity among peripheral T cells is an important factor contributing to the diversity of T-cell responses to foreign antigens.
- Klíčová slova
- AIMT, CD5, NUR77, T cell, TCR, self-antigen, self-reactivity, tolerance, virtual memory,
- MeSH
- aktivace lymfocytů imunologie MeSH
- autoantigeny imunologie MeSH
- CD4-pozitivní T-lymfocyty imunologie metabolismus MeSH
- CD8-pozitivní T-lymfocyty imunologie metabolismus MeSH
- jaderné receptory - podrodina 4, skupina A, člen 1 imunologie metabolismus MeSH
- lidé MeSH
- receptory antigenů T-buněk imunologie metabolismus MeSH
- thymocyty cytologie imunologie MeSH
- thymus cytologie imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- autoantigeny MeSH
- jaderné receptory - podrodina 4, skupina A, člen 1 MeSH
- NR4A1 protein, human MeSH Prohlížeč
- receptory antigenů T-buněk MeSH
An efficient way to generate [(L)CuO]+ complexes with a number of monodentate and bidentate ligands (L) from their [(L)Cu(ClO3 )]+ precursors by electrospray ionization was herein explored. Further, we studied [(L)CuO]+ with L=9,10-phenanthraquinone, 1,10-phenanthroline, and acetonitrile in detail. The signature of these terminal copper-oxo complexes was found to be elimination of the oxygen atom upon collisional activation. We investigated and compared their reactions with water, ethane, ethylene, and 1,4-cyclohexadiene. The [(MeCN)CuO]+ complex oxidized water and performed C-H activation and hydroxylation of ethane. The complexes with bidentate ligands did not react with water and oxidized only larger hydrocarbons. All the investigated complexes showed comparable reactivities in the oxygen-transfer reaction with ethylene.
- Klíčová slova
- C−H activation, IR spectroscopy, copper, gas-phase reactivity, oxygen transfer,
- Publikační typ
- časopisecké články MeSH
The high specific surface area and high reactivity of nanoscale zero-valent iron (nZVI) particles have led to much research on their application to environmental remediation. The reactivity of nZVI is affected by both the water chemistry and the properties of the particular type of nZVI particle used. We have investigated the reactivity of three types of commercially available Nanofer particles (from Nanoiron, s.r.o., Czech Republic) that are currently either used in, or proposed for use in full scale environmental remediation projects. The performance of one of these, the air-stable and thus easy-to-handle Nanofer Star particle, has not previously been reported. Experiments were carried out first in batch shaking reactors in order to derive maximum reactivity rates and provide a rapid estimate of the Nanofer particle's reactivity. The experiments were performed under near-natural environmental conditions with respect to the pH value of water and solute concentrations, and results were compared with those obtained using synthetic water. Thereafter, the polyelectrolyte-coated Nanofer 25S particles (having the highest potential for transport within porous media) were chosen for the experiments in column reactors, in order to elucidate nanoparticle reactivity under a more field-site realistic setting. Iopromide was rapidly dehalogenated by the investigated nZVI particles, following pseudo-first-order reaction kinetics that was independent of the experimental conditions. The specific surface area normalized reaction rate constant (kSA) value in the batch reactors ranged between 0.12 and 0.53Lm(-2)h(-1); it was highest for the uncoated Nanofer 25 particles, followed by the polyacrylic acid-coated Nanofer 25S and air-stable Nanofer Star particles. In the batch reactors all particles were less reactive in natural water than in synthetic water. The kSA values derived from the column reactor experiments were about 1000 times lower than those from the batch reactors, ranging between 2.6×10(-4) and 5.7×10(-4)Lm(-2)h(-1). Our results revealed that the easy-to-handle and air-stable Nanofer Star particles are the least reactive of all the Nanofer products tested. The reaction kinetics predicted by column experiments were more realistic than those predicted by batch experiments and these should therefore be used when designing a full-scale field application of nanomaterials for environmental remediation.
- Klíčová slova
- Batch reactor, Column reactor, Iopromide, Nanofer, Nanoscale zero-valent iron, Reactivity,
- MeSH
- akrylové pryskyřice chemie MeSH
- johexol analogy a deriváty chemie MeSH
- kinetika MeSH
- koncentrace vodíkových iontů MeSH
- nanočástice chemie MeSH
- poréznost MeSH
- regenerace a remediace životního prostředí MeSH
- voda chemie MeSH
- železo chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- akrylové pryskyřice MeSH
- carbopol 940 MeSH Prohlížeč
- iopromide MeSH Prohlížeč
- johexol MeSH
- voda MeSH
- železo MeSH
The extensive use of nanoscale zero-valent iron (nZVI) particles for groundwater treatment has been limited, in part, because of their non-selective reactivity and low mobility in aquatic environments. Herein, we describe and explore progressive changes in the reactivity and migration of aqueous dispersed nZVI particles under an applied DC electric field. Due to the applied electric field with an intensity of about 1 V cm-1, the solution oxidation-reduction potential (ORP) remained as low as -200 mV for at least 32 days, which was in agreement with the persistence of the reduced iron species (mainly Fe(II)), and led to substantially prolonged reactivity of the original nZVI. The treatment of chlorinated ethenes (DCE > PCE > TCE) was markedly faster, individual CHC compounds were eliminated with the same kinetics and no lesser-chlorinated intermediates were accumulated, following thus the direct dechlorination scheme. When nZVI-dispersion flows towards the anode through vertical laboratory columns filled with quartz sand, significant enhancement of nZVI migration was recorded because of lower extent of nanoparticle aggregation and increased repulsion forces between the nanoparticles and the surface of silica dioxide. The results of this study have significant consequences for groundwater remediation, mainly for the treatment of slowly degradable DCE in real CHC contaminated groundwater, where it could improve the reactivity, the longevity and the migration of nZVI particles.
- Klíčová slova
- Direct dechlorination, Electric field, Enhanced properties, Migration, Reactivity, nZVI,
- MeSH
- chemické látky znečišťující vodu * MeSH
- kovové nanočástice * MeSH
- nanočástice * MeSH
- podzemní voda * MeSH
- trichlorethylen * MeSH
- železo MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chemické látky znečišťující vodu * MeSH
- trichlorethylen * MeSH
- železo MeSH
- MeSH
- gestační stáří MeSH
- lidé MeSH
- oxytocin aplikace a dávkování MeSH
- tachyfylaxe * MeSH
- těhotenství * MeSH
- uterus fyziologie MeSH
- vagina cytologie MeSH
- vaginální stěr MeSH
- Check Tag
- lidé MeSH
- těhotenství * MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- oxytocin MeSH
Alcohol abuse during pregnancy is a well-known factor in fetal morbidity, including smaller fetal size. We have shown that chronic hypoxia, considered the main pathogenetic factor in intrauterine growth restriction, elevates fetoplacental vascular resistance (and vasoconstrictor reactivity) and thus, presumably, reduces placental blood flow. We thus hypothesized that alcohol may affect the fetus - in addition to other mechanisms - by altering fetoplacental vascular resistance and/or reactivity. Using isolated, double-perfused rat placenta model, we found that maternal alcohol intake in the last third of gestation doubled the vasoconstrictor responses to angiotensin II but did not affect resting vascular resistance. Reactivity to acute hypoxic challenges was unchanged. Chronic maternal alcohol intake in a rat model alters fetoplacental vasculature reactivity; nevertheless, these changes do not appear as serious as other detrimental effects of alcohol on the fetus.
Cytomegalovirus (CMV) infection is associated with allograft rejection but the mechanisms behind are poorly defined yet. Although cross-reactivity of T cells to alloantigen and CMV has been hypothesized, direct evidence in patients is lacking. In this observational cohort study, we tested the pre-transplant effector/memory T cell response to CMV peptide pools and alloantigen in 78 living donor/recipient pairs using the interferon-gamma Enzyme-Linked ImmunoSpot (ELISPOT) assay. To prove the hypothesis of cross-reactivity, we analyzed by applying next-generation sequencing the T cell receptor ß (TCR- ß) repertoire of CMV- and alloantigen-reactive T cells enriched from peripheral pre-transplant blood of 11 CMV-seropositive and HLA class I mismatched patients. Moreover, the TCR-repertoire was also analyzed in the allograft biopsies of those patients. There was a significant association between the presence of pre-transplant CMV immediate-early protein 1 (IE-1)-specific effector/memory T cells and acute renal allograft rejection and function (p = 0.01). Most importantly, we revealed shared TCR-ß sequences between CMV-IE1 and donor alloantigen-reactive T cells in all pre-transplant peripheral blood samples analyzed in CMV-seropositive patients who received HLA class I mismatched grafts. Identical TCR sequences were also found in particular in post-transplant allograft biopsies of patients with concomitant CMV infection and rejection. Our data show the presence of functional, cross-reactive T cells and their clonotypes in peripheral blood and in kidney allograft tissue. It is therefore likely that CMV-donor cross-reactivity as well as CMV specific T cell elicited inflammation is involved in the processes that affect allograft outcomes.
- Klíčová slova
- ELISPOT, TCR repertoire, cross-reactivity, cytomegalovirus, heterologous immunity, kidney transplantation, rejection,
- MeSH
- alografty MeSH
- biopsie MeSH
- cytomegalovirové infekce * etiologie genetika imunologie patologie MeSH
- Cytomegalovirus imunologie MeSH
- dospělí MeSH
- imunologická paměť * MeSH
- isoantigeny genetika imunologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- receptory antigenů T-buněk alfa-beta * imunologie MeSH
- T-lymfocyty * mikrobiologie patologie MeSH
- transplantace ledvin * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- isoantigeny MeSH
- receptory antigenů T-buněk alfa-beta * MeSH
