RESUMO
An understanding of the consequences of oxidative/halogenative stress triggered by neutrophil activation is impossible without considering NETosis. NETosis, formation of neutrophil extracellular traps (NETs), is known to promote microthrombus formation and impair wound healing in type 2 diabetes mellitus (T2DM) patients. Therefore, there is a need to search for drugs and treatment approaches that could prevent excessive NET formation. We aimed to evaluate the effect of vitamin D3 in combination with omega-3 polyunsaturated fatty acids (vitamin D3/omega-3 PUFAs) on NETosis in T2DM patients with purulent necrotizing lesions of the lower extremities. Patients and healthy subjects had vitamin D3 deficiency. Patients received, beyond standard treatment, 6000 IU of vitamin D3 and 480 mg of omega-3 PUFAs, and healthy subjects 1000 IU of vitamin D3 and 240 mg of omega-3 PUFAs daily for seven days. Neutrophil activation in ex vivo blood by phorbol-12-myristate-13-acetate (PMA) was used as a NETosis model. The percentage of blood NETs relative to leukocytes (NETbackground) before vitamin D3/omega-3 PUFA supplementation was 3.2%-4.9% in healthy subjects and 1.7%-10.8% in patients. These values rose, respectively, to 7.7%-9.1% and 4.0%-17.9% upon PMA-induced NETosis. In addition, the leukocyte count decreased by 700-1300 per 1 µL in healthy subjects and 700-4000 per 1 µL in patients. For both patients and healthy subjects, taking vitamin D3/omega-3 PUFAs had no effect on NETbackground but completely inhibited PMA-induced NET formation, though neutrophils exhibited morphological features of activation. Also, leukocyte loss was reduced (to 500 per 1 µL). For patients on standard treatment alone, changes occurred neither in background NETs and leukocytes nor in their amount after PMA stimulation. The decreased ability of neutrophils to generate NETs, which can be achieved by vitamin D3/omega-3 PUFA supplementation, could have a positive effect on wound healing in T2DM patients and reduce the incidence and severity of complications.
Assuntos
Colecalciferol/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Armadilhas Extracelulares/efeitos dos fármacos , Ácidos Graxos Ômega-3/uso terapêutico , Úlcera da Perna/tratamento farmacológico , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Deficiência de Vitamina D/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Células Cultivadas , Colecalciferol/efeitos adversos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Quimioterapia Combinada , Ácido Eicosapentaenoico/uso terapêutico , Armadilhas Extracelulares/metabolismo , Ácidos Graxos Ômega-3/efeitos adversos , Feminino , Humanos , Úlcera da Perna/sangue , Úlcera da Perna/diagnóstico , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Projetos Piloto , Fatores de Tempo , Resultado do Tratamento , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Cicatrização/efeitos dos fármacosRESUMO
Hypochlorous acid (HOCl), one of the major precursors of free radicals in body cells and tissues, is endowed with strong prooxidant activity. In living systems, dinitrosyl iron complexes (DNIC) with glutathione ligands play the role of nitric oxide donors and possess a broad range of biological activities. At micromolar concentrations, DNIC effectively inhibit HOCl-induced lysis of red blood cells (RBCs) and manifest an ability to scavenge alkoxyl and alkylperoxyl radicals generated in the reaction of HOCl with tert-butyl hydroperoxide. DNIC proved to be more effective cytoprotective agents and organic free radical scavengers in comparison with reduced glutathione (GSH). At the same time, the kinetics of HOCl-induced oxidation of glutathione ligands in DNIC is slower than in the case of GSH. HOCl-induced oxidative conversions of thiolate ligands cause modification of DNIC, which manifests itself in inclusion of other ligands. It is suggested that the strong inhibiting effect of DNIC with glutathione on HOCl-induced lysis of RBCs is determined by their antioxidant and regulatory properties.
Assuntos
Citoproteção/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Glutationa/farmacologia , Hemólise/efeitos dos fármacos , Ácido Hipocloroso/toxicidade , Ferro/farmacologia , Óxidos de Nitrogênio/farmacologia , Substâncias Protetoras/farmacologia , Albuminas/metabolismo , Glutationa/química , Humanos , Ferro/química , Ligantes , Óxidos de Nitrogênio/química , Peroxidase/metabolismoRESUMO
A dispersion interferometer based on the second-harmonic generation of a carbon dioxide laser in orientation-patterned gallium arsenide has been developed for measuring electron density in plasmas. The interferometer includes two nonlinear optical crystals placed on opposite sides of the plasma. This instrument has been used to measure electron line densities in a pulsed radio-frequency generated argon plasma. A simple phase-extraction technique based on combining measurements from two successive pulses of the plasma has been used. The noise-equivalent line density was measured to be 1.7 × 10(17) m(-2) in a detection bandwidth of 950 kHz. One of the orientation-patterned crystals produced 13 mW of peak power at the second-harmonic wavelength from a carbon dioxide laser with 13 W of peak power. Two crystals arranged sequentially produced 58 mW of peak power at the second-harmonic wavelength from a carbon dioxide laser with 37 W of peak power.
RESUMO
Two different realizations of time-reversal experiments of ultrafast waveforms are carried out in real time by use of four-wave mixing arrangements of spectrally decomposed waves. The first, conventional, method is based on phase conjugation of the waveform's spectrum and achieves time reversal of real amplitude waveforms. The second arrangement of the spectrally decomposed waves spatially inverts the waveform's spectrum with respect to the optical axis of the processor and achieves true time reversal for complex-amplitude ultrafast waveforms. We compare and contrast these two real-time techniques.
RESUMO
In response to a comment on our Letter [Opt. Lett. 25, 132 (2000)], we reiterate the distinction between the spectral inversion and the spectral phase conjugation processing techniques. The former achieves time reversal of the complex amplitude waveform, whereas the latter performs time reversal of the real electric field.
RESUMO
The operational characteristics of a time-to-space processor based on three-wave mixing for instantaneous imaging of ultrafast waveforms are investigated. We assess the effects of various system parameters on the processor's important attributes: time window of operation and signal conversion efficiency. Both linear and nonlinear operation regimes are considered, with use of a Gaussian pulse profile and a Gaussian spatial mode model. This model enables us to define a resolution measure for the processor, which is found to be an important characteristic. When the processor is operated in the linear interaction regime, we find that the conversion efficiency of a temporal signal to a spatial image is inversely proportional to the resolution measure. In the nonlinear interaction regime, nonuniform signal conversion due to fundamental wave depletion gives rise to a phenomenon that can be used to enhanced the imaging operation. We experimentally verify this nonlinear operation.
RESUMO
A nonlinear optical processor that is capable of true real-time conversion of spatial-domain images to ultrafast time-domain optical waveforms is presented. The method is based on four-wave mixing between the optical waves of spectrally decomposed ultrashort pulses and spatially Fourier-transformed quasi-monochromatic images. To achieve efficient wave mixing at a femtosecond rate we utilize a cascaded second-order nonlinearity arrangement in a beta-barium borate crystal with type II phase matching. We use this ultrafast technique to experimentally generate several complex-amplitude temporal waveforms, with efficiency as high as 10%, by virtue of the cascaded nonlinearity arrangement.