Precision dosing of perampanel in pediatric patients receiving oxcarbazepine combination therapy: physiologically based pharmacokinetic modeling and simulation.

Background: The combination of oxcarbazepine (OXC) with perampanel (PER) considerably reduces the blood concentration of PER in children, decreasing the antiepileptic effect of PER. This study aimed to predict PER exposure and provide recommendations for dose adjustment in pediatric patients.

Research Design And Methods: Physiologically based pharmacokinetic (PBPK) models of PER and OXC for adults and pediatrics were developed and verified, followed by drug - drug interaction (DDI) modeling and validation of the models against available pharmacokinetic data.

Physiologically based pharmacokinetic model for oxcarbazepine active metabolite to predict pharmacokinetics in paediatric patients with renal impairment and adjust dosages.

Aims: Oxcarbazepine (OXC) has been approved as monotherapy or adjunctive therapy for paediatric partial seizures. There are few reports on the pharmacokinetics (PK) of OXC in paediatric patients with renal impairment (RI), especially dosage studies of RI, which are rarely conducted on paediatric patients. This study aimed to predict the PK of OXC in children with RI and to provide recommendations for dose adjustment in this population.

Integrated microdevice for long-term automated perfusion culture without shear stress and real-time electrochemical monitoring of cells.

Electrochemical techniques based on ultramicroelectrodes (UMEs) play a significant role in real-time monitoring of chemical messengers' release from single cells. Conversely, precise monitoring of cells in vitro strongly depends on the adequate construction of cellular physiological microenvironment. In this paper, we developed a multilayer microdevice which integrated high aspect ratio poly(dimethylsiloxane) (PDMS) microfluidic device for long-term automated perfusion culture of cells without shear stress and an independently addressable microelectrodes array (IAMEA) for electrochemical monitoring of the cultured cells in real time.

Real-time monitoring of oxidative burst from single plant protoplasts using microelectrochemical sensors modified by platinum nanoparticles.

Oxidative bursts from plants play significant roles in plant disease defense and signal transduction; however, it has not hitherto been investigated on individual living plant cells. In this article, we fabricated a novel sensitive electrochemical sensor based on electrochemical deposition of Pt nanoparticles on the surface of carbon fiber microdisk electrodes via a nanopores containing polymer matrix, Nafion. The numerous hydrophilic nanochannels in the Nafion clusters coated on the electrode surface served as the molecular template for the deposition and dispersion of Pt, which resulted in the uniform construction of small Pt nanoparticles.

Monitoring of vesicular exocytosis from single cells using micrometer and nanometer-sized electrochemical sensors.

Communication between cells by release of specific chemical messengers via exocytosis plays crucial roles in biological process. Electrochemical detection based on ultramicroelectrodes (UMEs) has become one of the most powerful techniques in real-time monitoring of an extremely small number of released molecules during very short time scales, owing to its intrinsic advantages such as fast response, excellent sensitivity, and high spatiotemporal resolution. Great successes have been achieved in the use of UME methods to obtain quantitative and kinetic information about released chemical messengers and to reveal the molecular mechanism in vesicular exocytosis.

Recent advances in single-cell analysis using capillary electrophoresis and microfluidic devices.

Cells are the fundamental unit of life, and studies on cell contribute to reveal the mystery of life. However, since variability exists between individual cells even in the same kind of cells, increased emphasis has been put on the analysis of individual cells for getting better understanding on the organism functions. During the past two decades, various techniques have been developed for single-cell analysis.

Indirect determination of pyruvic acid by capillary electrophoresis with amperometric detection.

A method of indirectly measuring pyruvic acid (PA) by capillary electrophoresis with amperometric detection is proposed for the first time. It is based on the oximation reaction between PA and hydroxylamine (NH(2)OH), and the quantification of PA was performed by direct and sensitive amperometric detection of excessive NH(2)OH after the oximation reaction. This method displayed a good sensitivity, and the detection limits of NH(2)OH and PA are 1.

Capillary electrophoretic immunoassay for alpha-fetoprotein with chemiluminescence detection.

A capillary electrophoretic immunoassay with chemiluminescence detection (CEIA-CL) using a non-competitive format for analyzing tumor marker alpha-fetoprotein (AFP) has been developed. In this method, antigen (Ag) AFP reacts with an excess amount of horseradish peroxidase (HRP)-labeled antibody (Ab*). The free Ab* and the bound Ab*-Ag complex produced in the solution are separated by CE in a separation capillary.

Carbon fiber nanoelectrodes applied to microchip electrophoresis amperometric detection of neurotransmitter dopamine in rat pheochromocytoma (PC12) cells.

Microelectrodes have been adopted in electrochemical detection for CE or microchip CE in recent years. In this paper, the use of nanoelectrodes (with tip diameter of 100-300 nm) as the electrochemical detector in microchip CE is firstly reported. The experimental results indicated that both the sensitivity and resolution of microchip CE with the carbon fiber nanoelectrode (CFNE) amperometric detection have been improved markedly comparing with the traditional microelectrodes.

Monitoring the reaction of hemoglobin with hydrogen peroxide by capillary electrophoresis-chemiluminescence detection.

The reaction of hemoglobin (Hb) with hydrogen peroxide (H2O2) leads to fluorescent product and heme degradation. We applied capillary electrophoresis-chemiluminescence (CE-CL) detection to monitor the course of Hb reacting with H2O2. Hb and released free iron ion (Fe3+) were detected based on their enhancement effects on CL of the luminol-H2O2 system.

Monitoring dopamine release from single living vesicles with nanoelectrodes.

Carbon fiber nanoelectrodes (tip diameter = ca. 100 nm) have been first used to monitor real-time dopamine release from single living vesicles of single rat pheochromocytoma (PC12) cells. The experiments show that active and inactive release sites exist on the surface of cells, and the spatial distributions have been differentiated even in the same active release zone.

Transport, location, and quantal release monitoring of single cells on a microfluidic device.

A novel microfluidic device has been developed for on-chip transport, location, and quantal release monitoring of single cells. The microfluidic device consists of a plate of PDMS containing channels for introducing cells and stimulants and a glass substrate into which a cell micro-chamber was etched. The two tightly reversibly sealed plates can be separated for respective cleaning, which significantly extends the lifetime of the microchip that is frequently clogged in cell analysis experiments.

Carbon fiber nanoelectrodes modified by single-walled carbon nanotubes.

Microelectrode voltammetry has been considered to be a powerful technique for single biological cell analysis and brain research. In this paper, we have developed a simple method to get highly sensitive carbon fiber nanoelectrodes (CFNE) modified by single-walled carbon nanotubes (SWNTs) on the basis of our previous work. The electrochemical behavior of SWNTs/CFNE was characterized by potassium ferricyanide, dopamine (DA), epinephrine (E), and norepinephrine (NE) using cyclic voltammetry (CV).

Separation of biogenic amines by micellar electrokinetic chromatography with on-line chemiluminescence detection.

A method of on-line chemiluminescence detection with capillary electrophoresis for biogenic amines (diaminopropane, putrescine, cadaverine and diaminohexane) labeled with N-(4-aminobutyl)-N-ethylisoluminol is reported for the first time. Two separation modes, capillary zone electrophoresis and micellar electrokinetic chromatography (MEKC), were studied. The results show that excellent resolution was achieved in MEKC.

Elemental speciation analysis in capillary electrophoresis.

The growing awareness of the strong development of the toxicity of heavy metals upon their chemical forms has led to an increasing interest in the qualitative and quantitative determination of specific metal species. Speciation has therefore become an important topic of present-day analytical research. The development in the elemental speciation analysis by capillary electrophoresis (CE) is reviewed.

Ultrasensitive chemiluminescence detection in capillary electrophoresis.

Capillary electrophoresis techniques offer high plate numbers and are highly suited for the efficient separations of a wide variety of chemical components in diverse matrices. Because of the small capillary and detection cell dimensions, together with the minute volumes of samples to be injected, sensitive detection schemes based on different physicochemical principles are being developed. One logical approach to increased sensitivity in capillary electrophoresis detection has been the development of chemiluminescence-based detectors.

Influence of soluble polymer polyvinylpyrrolidone on separation of small peptides and amino acids by microchip-based capillary electrophoresis.

In microchip-based capillary electrophoresis, the resolution and separation efficiency of small peptides and amino acids can be noticeably improved by adding a low molecular weight (30,000) soluble polymer additive, polyvinypyrrolidone in the separation medium. Several separation conditions such as injection time and electrophoretic buffer have been investigated and optimized. Using an electro-stacking scheme, the resolution and separation efficiency of small peptides and amino acids can be enhanced significantly.

Microchip capillary electrophoresis with electrochemical detection.

A novel microchip capillary electrophoresis system with electrochemical detection, using the replaceable microelectrode, is first reported. This kind of electrode can be fabricated in general laboratories and can be replaced quickly with electrodes of different materials according to the requirements of experiments. The end-column electrochemical detection on microchip CE was achieved by fixing the working electrode (such as carbon fiber, Pt, or Au, etc.

Highly sensitive chemiluminescence detection of copper(II) in capillary electrophoresis with field-amplified sample injection.

Field-amplified sample injection of copper(II) was investigated using capillary electrophoresis with chemiluminescence detection. The sensitivity of copper(II) has been improved markedly by the field-amplified sample injection technique and the detection limit reaches 2 x 10(-11) M. By injection of a short plug of water before sample introduction, the sensitivity can be further improved 5-fold and the detection limit reaches 4 x 10(-12) M.