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1.
Nano Lett ; 24(38): 11895-11903, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39265047

RESUMO

Shallow nitrogen-vacancy (NV) centers in diamond offer opportunities to study photochemical reactions, including photogeneration of radical pairs, at the single-molecule regime. A prerequisite is a detailed understanding of charge and spin dynamics of NVs exposed to the short-wavelength light required to excite chemical species. Here, we investigate the charge and spin dynamics of shallow NVs under 445 and 375 nm illumination. With blue excitation, charge-state preparation is power-dependent, and modest spin initialization fidelity is observed. Under UV excitation, charge-state preparation is power-independent and no spin polarization is observed. Aging of NVs under prolonged UV exposure manifests in a reduced charge stability and spin contrast. We attribute this aging to modified local charge environments of near-surface NVs and identify distinct electronic traps only accessible at short wavelengths. Finally, we evaluate the prospects of NVs to probe photogenerated radical pairs based on measured sensitivities and outline possible sensing schemes.

2.
Sensors (Basel) ; 24(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39275443

RESUMO

The detection of electric fields in the environment has great importance for understanding various natural phenomena, environmental monitoring, and ensuring human safety. This review paper provides an overview of the current state-of-the-art technologies utilized for sensing electric fields in the environment, the challenges encountered, and the diverse applications of this sensing technology. The technology is divided into three categories according to the differences in the physical mechanism: the electro-optic effect-based measurement system, the MEMS-based sensor, and the newly reported quantum effect-based sensors. The principles of the underlying methods are comprehensively introduced, and the tentative applications for each type are discussed. Detailed comparisons of the three different techniques are identified and discussed with regard to the instrument, its sensitivity, and bandwidth. Additionally, the challenges faced in environmental electric field sensing, the potential solutions, and future development directions are addressed.

3.
Nanotechnology ; 35(49)2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292051

RESUMO

Emerging fields of quantum technologies and biomedical applications demand pure nanodiamonds (NDs) with well-defined surface chemistry. Therefore, an inexpensive, scalable and eco-friendly ND surface purification technology is required. In this study, we report our method, salt-coated air oxidation (SCAO) thermal annealing, to achieve uniform purification of a ND surface without the loss of diamond material. A photoluminescence (PL) spectroscopy quality control method is proposed to evaluate the degree of purification. The presence of an isoemission point in the set of nitrogen vacancy (NV) center PL spectra, obtained through the photochromic effect, is examined as a surface purity indicator. The ratio of the NV centers in NDs after the SCAO treatment was determined by decomposing the PL spectra using the non-negative matrix factorization technique.

4.
Nano Lett ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39319608

RESUMO

The intrinsic spin of the electron and its associated magnetic moment can provide insights into spintronics. However, the interaction is extremely weak, as is the case with the coupling between an electron's spin and a magnetic field, and it poses significant experimental challenges. Here we demonstrate the direct measurement of polarized single NV- centers and their spin-spin coupling behaviors in diamond. By using photoinduced magnetic force microscopy, we obtain the extremely weak magnetic force coupling originating from the electron spin. The polarized spin state of NV- centers, transitioning from |0⟩ to |±1⟩, and their corresponding Zeeman effect can be characterized through their interaction with a magnetic tip. The result presents an advancement in achieving electron spin measurements by magnetic force, avoiding the need for manufacturing conductive substrates. This facilitates a better understanding and control of electron spin to novel electronic states for future quantum technologies.

5.
Curr Pharm Des ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39161145

RESUMO

OBJECTIVE: Nv Zhen Er Xian He Ji (NZEXHJ) is used to treat perimenopausal syndrome (PS), but its effect on perimenopausal coronary heart disease is unclear. Furthermore, the aim of this research is to study the effect of NZEXHJ on perimenopausal coronary heart disease (PMCHD) in a rat model based on a network pharmacology approach. MATERIALS AND METHODS: Based on network pharmacological analysis combined with molecular docking, we predicted the potential therapeutic target and pharmacological mechanism of NZEXHJ in the treatment of PMCHD. We used an ovariectomized rat (OVR) model to understand the effect of NZEXHJ on myocardial injury and further verified the target of NZEXHJ in the intervention of PMCHD. RESULTS: We selected 52 active components of NZEXHJ against PMCHD and an intersection of their targets on network pharmacology, to which SCN5A, SER1, AR, and PGR were significantly correlated. The protein- protein interaction network revealed CASP3, CXCL8, IL6, MAPK1, TNF, TP53, and VEGFA in the treatment of PMCHD with NZEXHJ. Kaempferol, luteolin, and mistletoe presented good affinity towards the aforementioned targets by Molecular docking NZEXHJ exerted protecting cardiomyocytes for OVR. The mechanism was related to a reduction in the expression levels of the CXCL8, TNF, and regulating PI3K-AKT signaling pathways. CONCLUSION: This study reveals the potential multi-component, multi-target, and multi-pathway pharmacological effects of NZEXHJ and predicts its protection against myocardial infarction in ovariectomized rats through the PI3K Akt pathway, providing a theoretical basis for the treatment of PMCHD.

6.
Nano Lett ; 24(31): 9650-9657, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39012318

RESUMO

Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is caused by chronic exposure to toxic particles and gases, such as cigarette smoke. Free radicals, which are produced during a stress response to toxic particles, play a crucial role in disease progression. Measuring these radicals is difficult since the complex mixture of chemicals within cigarette smoke interferes with radical detection. We used a new quantum sensing technique called relaxometry to measure free radicals with nanoscale resolution on cells from COPD patients and healthy controls exposed to cigarette smoke extract (CSE) or control medium. Epithelial cells from COPD patients display a higher free radical load than those from healthy donors and are more vulnerable to CSE. We show that epithelial cells of COPD patients are more susceptible to the damaging effects of cigarette smoke, leading to increased release of free radicals.


Assuntos
Brônquios , Células Epiteliais , Doença Pulmonar Obstrutiva Crônica , Fumaça , Humanos , Radicais Livres , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células Epiteliais/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Fumaça/efeitos adversos , Brônquios/citologia , Brônquios/efeitos dos fármacos , Nicotiana/química , Células Cultivadas , Fumar/efeitos adversos , Produtos do Tabaco/análise , Produtos do Tabaco/efeitos adversos
7.
Nano Lett ; 24(31): 9711-9719, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39052913

RESUMO

Nitrogen-vacancy (NV-) centers in nanodiamonds have emerged as a versatile platform for a wide range of applications, including bioimaging, photonics, and quantum sensing. However, the widespread adoption of nanodiamonds in practical applications has been hindered by the challenges associated with patterning them into high-resolution features with sufficient throughput. In this work, we overcome these limitations by introducing a direct laser-writing bubble printing technique that enables the precise fabrication of two-dimensional nanodiamond patterns. The printed nanodiamonds exhibit a high packing density and strong photoluminescence emission, as well as robust optically detected magnetic resonance (ODMR) signals. We further harness the spatially resolved ODMR of the nanodiamond patterns to demonstrate the mapping of two-dimensional temperature gradients using high frame rate widefield lock-in fluorescence imaging. This capability paves the way for integrating nanodiamond-based quantum sensors into practical devices and systems, opening new possibilities for applications involving high-resolution thermal imaging and biosensing.

8.
ACS Appl Mater Interfaces ; 16(28): 37226-37233, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38976775

RESUMO

Thanks to its low or negative surface electron affinity and chemical inertness, diamond is attracting broad attention as a source material of solvated electrons produced by optical excitation of the solid-liquid interface. Unfortunately, its wide bandgap typically imposes the use of wavelengths in the ultraviolet range, hence complicating practical applications. Here, we probe the photocurrent response of water surrounded by single-crystal diamond surfaces engineered to host shallow nitrogen-vacancy (NV) centers. We observe clear signatures of diamond-induced photocurrent generation throughout the visible range and for wavelengths reaching up to 594 nm. Experiments as a function of laser power suggest that NV centers and other coexisting defects─likely in the form of surface traps─contribute to carrier injection, though we find that NVs dominate the system response in the limit of high illumination intensities. Given our growing understanding of near-surface NV centers and adjacent point defects, these results open new perspectives in the application of diamond-liquid interfaces to photocarrier-initiated chemical and spin processes in fluids.

9.
Micromachines (Basel) ; 15(7)2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39064422

RESUMO

A single nitrogen-vacancy (NV) center in a diamond can be used as a nanoscale sensor for magnetic field, electric field or nuclear spins. Due to its low photon detection efficiency, such sensing processes often take a long time, suffering from an electron spin resonance (ESR) frequency fluctuation induced by the time-varying thermal perturbations noise. Thus, suppressing the thermal noise is the fundamental way to enhance single-sensor performance, which is typically achieved by utilizing a thermal control protocol with a complicated and highly costly apparatus if a millikelvin-level stabilization is required. Here, we analyze the real-time thermal drift and utilize an active way to alternately track the single-spin ESR frequency drift in the experiment. Using this method, we achieve a temperature stabilization effect equivalent to sub-millikelvin (0.8 mK) level with no extra environmental thermal control, and the spin-state readout contrast is significantly improved in long-lasting experiments. This method holds broad applicability for NV-based single-spin experiments and harbors the potential for prospective expansion into diverse nanoscale quantum sensing domains.

10.
Nanotechnol Sci Appl ; 17: 147-166, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39081854

RESUMO

Introduction: As nanodiamonds become more and more widely used for intracellular labelling and measurements, the task of delivering these nanoparticles inside cells becomes more and more important. Certain cell types easily take up nanodiamonds, while others require special procedures. Methods: In previous research, we found that HT-29 cells (a colon cancer cell line), which are notoriously difficult in the context of nanodiamond internalization, show increased uptake rates, when pre-treated with trypsin- ethylenediaminetetraacetic acid (trypsin-EDTA). However, the uptake mechanism has not been studied before. This article focuses on a more detailed investigation of the reasons underlying this phenomenon. We start by identifying the timing of fluorescent nanodiamond (FND) uptake in trypsin-EDTA pre-treated cells. We then use a combination of chemical inhibitors and Immunocytochemistry to identify the main pathways employed by HT-29 cells in the internalization process. Results and Discussion: We investigate how these pathways are affected by the trypsin-EDTA pre-treatment and conclude by offering possible explanations for this phenomenon. We found that nanodiamonds are internalized via different pathways. Clathrin-mediated endocytosis proves to be the dominating mechanism. Trypsin-EDTA treatment increases particle uptake and affects the uptake mechanism.

11.
Biomater Adv ; 162: 213927, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38917649

RESUMO

Metals are widely utilized as implant materials for bone fixtures as well as stents. Biodegradable versions of these implants are highly desirable since patients do not have to undergo a second surgery for the materials to be removed. Attractive options for such materials are zinc silver alloys since they also offer the benefit of being antibacterial. However, it is important to investigate the effect of the degradation products of such alloys on the surrounding cells, taking into account silver cytotoxicity. Here we investigated zinc alloyed with 1 % of silver (Zn1Ag) and how differently concentrated extracts (1 %-100 %) of this material impact human umbilical vein endothelial cells (HUVECs). More specifically, we focused on free radical generation and oxidative stress as well as the impact on cell viability. To determine free radical production we used diamond-based quantum sensing as well as conventional fluorescent assays. The viability was assessed by observing cell morphology and the metabolic activity via the MTT assay. We found that 1 % and 10 % extracts are well tolerated by the cells. However, at higher extract concentrations we observed severe impact on cell viability and oxidative stress. We were also able to show that quantum sensing was able to detect significant free radical generation even at the lowest tested concentrations.


Assuntos
Ligas , Sobrevivência Celular , Células Endoteliais da Veia Umbilical Humana , Nanodiamantes , Estresse Oxidativo , Zinco , Humanos , Ligas/química , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Nanodiamantes/química , Prata/toxicidade , Prata/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Radicais Livres/metabolismo , Teste de Materiais/métodos , Implantes Absorvíveis/efeitos adversos
12.
Micromachines (Basel) ; 15(6)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38930649

RESUMO

Visualizing the near-field distribution of microwave field in a monopole antenna is very important for antenna design and manufacture. However, the traditional method of measuring antenna microwave near field distribution by mechanical scanning has some problems, such as long measurement time, low measurement accuracy and large system volume, which seriously limits the measurement effect of antenna microwave near field distribution. In this paper, a method of microwave near-field imaging of a monopole antenna using a nitrogen-vacancy center diamond is presented. We use the whole diamond as a probe and camera to achieve wide-field microwave imaging. Because there is no displacement structure in the system, the method has high time efficiency and good stability. Compared with the traditional measurement methods, the diamond probe has almost no effect on the measured microwave field, which realizes the accurate near-field imaging of the microwave field of the monopole antenna. This method achieves microwave near-field imaging of a monopole antenna with a diameter of 100 µm and a length of 15 mm at a field of view of 5 × 5 mm, with a spatial resolution of 3 µm and an imaging bandwidth of 2.7~3.2 GHz, and an optimal input microwave phase resolution of 0.52° at a microwave power of 0.8494 W. The results provide a new method for microwave near-field imaging and measurement of monopole antennas.

13.
Micromachines (Basel) ; 15(5)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38793235

RESUMO

High-dynamic-range integrated magnetometers demonstrate extensive potential applications in fields involving complex and changing magnetic fields. Among them, Diamond Nitrogen Vacancy Color Core Magnetometer has outstanding performance in wide-range and high-precision magnetic field measurement based on its inherent high spatial resolution, high sensitivity and other characteristics. Therefore, an innovative frequency-tracking scheme is proposed in this study, which continuously monitors the resonant frequency shift of the NV color center induced by a time-varying magnetic field and feeds it back to the microwave source. This scheme successfully expands the dynamic range to 6.4 mT, approximately 34 times the intrinsic dynamic range of the diamond nitrogen-vacancy (NV) center. Additionally, it achieves efficient detection of rapidly changing magnetic field signals at a rate of 0.038 T/s.

14.
Sensors (Basel) ; 24(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38793993

RESUMO

Long coherence times at room temperature make the NV center a promising candidate for quantum sensors and quantum computers. The necessary coherent control of the electron spin triplet in the ground state requires microwave π pulses in the nanosecond range, obtained from the Rabi oscillation of the mS spin states of the magnetic resonances of the NV centers. Laboratory equipment has a high temporal resolution for these measurements but is expensive and, therefore, uninteresting for fields such as education. In this work, we present measurement electronics for NV centers that are optimized for microcontrollers. It is shown that the Rabi frequency is linear to the output of the digital-to-analog converter (DAC) and is used to adapt the time length π of the electron spin flip, to the limited pulse width resolution of the microcontroller. This was achieved by breaking down the most relevant functions of conventional laboratory devices and replacing them with commercially available integrated components. The result is a cost-effective handheld setup for coherent control applications of NV centers.

15.
Nano Lett ; 24(19): 5754-5760, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38708987

RESUMO

Two-dimensional (2D) FenGeTe2, with n = 3, 4, and 5, has been realized in experiments, showing strong magnetic anisotropy with enhanced critical temperature (Tc). The understanding of its magnetic anisotropy is crucial for the exploration of more stable 2D magnets and its spintronic applications. Here, we report a quantitative reconstruction of the magnetization magnitude and its direction in ultrathin Fe4GeTe2 using nitrogen vacancy centers. Through imaging stray magnetic fields, we identified the spin-flop transition at approximately 80 K, resulting in a change of the easy axis from the out-of-plane direction to the in-plane direction. Moreover, by analyzing the thermally activated escape behavior of the magnetization near Tc in terms of the Ginzburg-Landau model, we observed the in-plane magnetic anisotropy effect and the formation capability of magnetic domains at ∼0.4 µm2 µT-1. Our findings contribute to the quantitative understanding of the magnetic anisotropy effect in a vast range of 2D van der Waals magnets.

16.
Virulence ; 15(1): 2360133, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38803081

RESUMO

Norovirus (NV) infection causes acute gastroenteritis in children and adults. Upon infection with NV, specific CD8+ T cells, which play an important role in anti-infective immunity, are activated in the host. Owing to the NV's wide genotypic variability, it is challenging to develop vaccines with cross-protective abilities against infection. To aid effective vaccine development, we examined specific CD8+ T-cell responses towards viral-structural protein (VP) epitopes, which enable binding to host susceptibility receptors. We isolated peripheral blood mononuclear cells from 196 participants to screen and identify predominant core peptides towards NV main and small envelope proteins using ex vivo and in vitro intracellular cytokine staining assays. Human leukocyte antigen (HLA) restriction characteristics were detected using next-generation sequencing. Three conservative immunodominant VP-derived CD8+ T-cell epitopes, VP294-102 (TDAARGAIN), VP2153-161 (RGPSNKSSN), and VP1141-148 (FPHIIVDV), were identified and restrictively presented by HLA-Cw * 0102, HLA-Cw * 0702, and HLA-A *1101 alleles, separately. Our findings provide useful insights into the development of future vaccines and treatments for NV infection.


Assuntos
Linfócitos T CD8-Positivos , Infecções por Caliciviridae , Proteínas do Capsídeo , Epitopos de Linfócito T , Gastroenterite , Norovirus , Humanos , Linfócitos T CD8-Positivos/imunologia , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/genética , Infecções por Caliciviridae/imunologia , Infecções por Caliciviridae/virologia , Norovirus/imunologia , Norovirus/genética , Adulto , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Masculino , Gastroenterite/virologia , Gastroenterite/imunologia , Feminino , Pessoa de Meia-Idade , Adulto Jovem , Criança , Adolescente , Leucócitos Mononucleares/imunologia , Epitopos Imunodominantes/imunologia , Pré-Escolar , Idoso
17.
ACS Sens ; 9(5): 2440-2446, 2024 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-38743437

RESUMO

Ultraviolet (UV) radiation is known to cause skin issues, such as dryness, aging, and even cancer. Among UV rays, UVB stands out for its ability to trigger problems within cells, including mitochondrial dysfunction, oxidative stress, and DNA damage. Free radicals are implicated in these cellular responses, but they are challenging to measure due to their short lifetime and limited diffusion range. In our study, we used a quantum sensing technique (T1 relaxometry) involving fluorescent nanodiamonds (FNDs) that change their optical properties in response to magnetic noise. This allowed us to monitor the free radical presence in real time. To measure radicals near mitochondria, we coated FNDs with antibodies, targeting mitochondrial protein voltage-dependent anion channel 2 (anti-VDAC2). Our findings revealed a dynamic rise in radical levels on the mitochondrial membrane as cells were exposed to UVB (3 J/cm2), with a significant increase observed after 17 min.


Assuntos
Queratinócitos , Mitocôndrias , Raios Ultravioleta , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Radicais Livres/química , Queratinócitos/efeitos da radiação , Queratinócitos/metabolismo , Pontos Quânticos/química , Pontos Quânticos/efeitos da radiação
18.
Nano Lett ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38588382

RESUMO

Nitrogen vacancy (NV) center-based magnetometry has been proven to be a versatile sensor for various classes of magnetic materials in broad temperature and frequency ranges. Here, we use the longitudinal relaxation time T1 of single NV centers to investigate the spin dynamics of nanometer-thin flakes of α-RuCl3 at room temperature. We observe a significant reduction in the T1 in the presence of α-RuCl3 in the proximity of NVs, which we attribute to paramagnetic spin noise confined in the 2D hexagonal planes. Furthermore, the T1 time exhibits a monotonic increase with an applied magnetic field. We associate this trend with the alteration of the spin and charge noise in α-RuCl3 under an external magnetic field. These findings suggest that the influence of the spin dynamics of α-RuCl3 on the T1 of the NV center can be used to gain information about the material itself and the technique to be used on other 2D materials.

19.
Nano Lett ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619219

RESUMO

Current density imaging is helpful for discovering interesting electronic phenomena and understanding carrier dynamics, and by combining pressure distributions, several pressure-induced novel physics may be comprehended. In this work, noninvasive, high-resolution two-dimensional images of the current density and pressure gradient for graphene ribbon and hBN-graphene-hBN devices are explored using nitrogen-vacancy (NV) centers in diamond under high pressure. The two-dimensional vector current density is reconstructed by the vector magnetic field mapped by the near-surface NV center layer in the diamond. The current density images accurately and clearly reproduce the complicated structure and current flow of graphene under high pressure. Additionally, the spatial distribution of the pressure is simultaneously mapped, rationalizing the nonuniformity of the current density under high pressure. The current method opens a significant new avenue to investigate electronic transport and conductance variations in two-dimensional materials and electrical devices under high pressure as well as for nondestructive evaluation of semiconductor circuits.

20.
Clin Ther ; 46(3): 217-227, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38485588

RESUMO

PURPOSE: NV-5138 ([S]-2-amino-5,5-difluoro-4,4-dimethylpentanoic acid) is an orally bioavailable, small-molecule activator of the mechanistic target of rapamycin complex 1 (mTORC1) pathway in development for treatment-resistant depression. The authors established a model to describe the relationship between plasma and cerebrospinal fluid (CSF) concentrations of NV-5138 and between CSF concentrations and potential biomarkers thought to be associated with mTORC1 activity (ie, orotic acid, N-acetylmethionine, and N-formylmethionine). METHODS: Data were collected from a randomized, double-blind, placebo-controlled, tolerability, and pharmacokinetic (PK) parameter study of 5 ascending (400, 800, 1600, 2400, and 3000 mg), once-daily oral doses of NV-5138 in healthy subjects. NV-5138 plasma PK parameter samples were collected at 15 time points over 24 hours on days 1 and 7, and at pre dose on days 2-6 for all doses. NV-5138 CSF PK parameter and CSF biomarker samples were collected on days 1 and 7 at pre dose and 4, 8, and 12 hours post dose for all doses except 3000 mg. A model-based approach was used to develop and validate a model that describes the relationship between NV-5138 in CSF and biomarker concentrations. FINDINGS: Twenty-four of the 42 enrolled subjects had simultaneous plasma and CSF measurements of NV-5138 and CSF biomarker concentrations and were included in the PK parameter and pharmacodynamic (PD) analyses. A 2-compartment plasma and CSF PK parameter, with indirect PD effects, model was developed and validated. NV-5138 plasma concentrations were positively correlated with those in CSF, although CSF concentrations lagged slightly behind those in plasma, as indicated by a counterclockwise hysteresis effect. Similarly, the relationship between the PD measures of mTORC1 activation and NV-5138 was also characterized by counterclockwise hysteresis, when the increase in CSF biomarker concentrations lagged behind those of NV-5138, consistent with a signaling intermediary/cascade, such as mTORC1. Maximal biomarker activation was achieved at NV-5138 CSF concentrations of approximately 3 µg/mL, which were associated with daily doses of 1600 mg NV-5138. The safety profile analysis (n = 42) found that most of the reported adverse events were mild in severity, with no severe, serious, unusual, or unexpected adverse events or any dissociative effects; 2 subjects (400-mg cohort) discontinued due to adverse events that were judged to be unrelated to study medication. IMPLICATIONS: The model will be used for designing future efficacy and tolerability studies. Consecutive daily doses of NV-5138 were well tolerated in this healthy volunteer study.


Assuntos
Voluntários Saudáveis , Leucina/análogos & derivados , Humanos , Área Sob a Curva , Biomarcadores , Método Duplo-Cego , Relação Dose-Resposta a Droga , Administração Oral
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