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1.
Nano Lett ; 20(8): 6104-6111, 2020 Aug 12.
Article in English | MEDLINE | ID: mdl-32677836

ABSTRACT

We demonstrate that a spin-torque nano-oscillator (STNO) rapidly sweep-tuned by a bias voltage can be used to perform an ultrafast time-resolved spectral analysis of frequency-manipulated microwave signals. The critical reduction in the time of the spectral analysis comes from the naturally small-time constants of a nanosized STNO (1-100 ns). The demonstration is performed on a vortex-state STNO generating in a frequency range around 300 MHz, when frequency down-conversion and matched filtering is used for signal processing. It is shown that this STNO-based spectrum analyzer can perform analysis of frequency-agile signals, having multiple rapidly changing frequency components with temporal resolution in a µs time scale and frequency resolution limited only by the "bandwidth" theorem. Our calculations show that using uniform magnetization state STNOs it would be possible to increase the operating frequency of a spectrum analyzer to tens of GHz.

2.
Drug Metab Dispos ; 47(9): 941-948, 2019 09.
Article in English | MEDLINE | ID: mdl-31248885

ABSTRACT

The majority of residents of the United States, Canada, and Europe are exposed to pyrethroids, the most commonly used class of insecticides. Surprisingly little is known about key aspects of their pharmacokinetics, including their mode of transport in the systemic circulation. This study tested the hypothesis that pyrethroids are transported by both plasma lipoproteins and proteins, similarly to other highly lipophilic environmental contaminants. Other aims were to characterize the binding of representative type I and II pyrethroids, and to compare their binding to rat versus human plasma. Binding of 14C-labeled cis-permethrin (CIS), trans-permethrin (TRANS) and deltamethrin (DLM) to proteins and lipoproteins was measured by sequential extraction of spiked plasma with isooctane, 2-octanol, and acetonitrile. Binding of DLM, CIS, and TRANS to plasma proteins and lipoproteins was linear from 250 to 750 nM; concentrations present in the plasma of orally dosed rats. Binding of DLM to high-density lipoprotein was twice that to low-density lipoprotein. Binding of DLM, CIS, and TRANS was ∼2-fold greater to proteins than to lipoproteins of rat and human plasma; albumin was primarily responsible for protein binding. Higher total binding of each pyrethroid to human (∼90%) than to rat (∼80%) plasma resulted from higher protein binding in human plasma. This was attributable in part to the higher albumin/protein content of human plasma. Rat albumin exhibited lower pyrethroid binding capacity than did human albumin. The results of this investigation indicate that albumin and lipoproteins play a major role in binding and transport of pyrethroids in the systemic circulation of both rats and humans.


Subject(s)
Blood Proteins/metabolism , Environmental Pollutants/pharmacokinetics , Insecticides/pharmacokinetics , Lipoproteins/metabolism , Administration, Oral , Adult , Animals , Brain/metabolism , Environmental Pollutants/administration & dosage , Environmental Pollutants/chemistry , Environmental Pollutants/toxicity , Humans , Insecticides/administration & dosage , Insecticides/chemistry , Insecticides/toxicity , Male , Nitriles/administration & dosage , Nitriles/chemistry , Nitriles/pharmacokinetics , Nitriles/toxicity , Permethrin/administration & dosage , Permethrin/chemistry , Permethrin/pharmacokinetics , Permethrin/toxicity , Protein Binding , Pyrethrins/administration & dosage , Pyrethrins/chemistry , Pyrethrins/pharmacokinetics , Pyrethrins/toxicity , Rats , Stereoisomerism , Tissue Distribution , Toxicity Tests, Acute
3.
Pediatr Res ; 79(3): 409-15, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26571224

ABSTRACT

BACKGROUND: To characterize the ontogeny of plasma albumin and total proteins, due to the lack of a comprehensive pediatric database. Secondly, to establish the magnitude and duration of maturational changes in binding of highly-bound drugs/chemicals. METHODS: Anonymized plasma samples from 296 donors were pooled in 6 age brackets from birth to adolescence. Total protein and albumin levels were measured in each age group, as was the age-dependency of plasma binding of diazepam (DZP), cyclosporine (CYC), and deltamethrin (DLM), a pyrethroid insecticide. RESULTS: Plasma levels of albumin and total proteins steadily increased for the first 1-3 y of life. Unbound DZP and CYC fractions were elevated three- to fourfold in neonates, but decreased to adult levels after 1 and 3 y, respectively. Unbound DLM levels exceeded those in adults for just 1 mo. CONCLUSION: Neonates and infants under 1-3 y may be at risk from increased amounts of free drug, when given standard doses of some highly-bound drugs. Pyrethroid insecticides might be anticipated to pose increased risk for 1 mo.


Subject(s)
Blood Proteins/chemistry , Cyclosporine/chemistry , Diazepam/chemistry , Nitriles/chemistry , Pyrethrins/chemistry , Serum Albumin/chemistry , Adolescent , Adult , Aged , Child , Child, Preschool , Cyclosporine/pharmacokinetics , Diazepam/pharmacokinetics , Female , Humans , Infant , Infant, Newborn , Insecticides/chemistry , Male , Middle Aged , Nitriles/pharmacokinetics , Protein Binding , Pyrethrins/pharmacokinetics , Young Adult
4.
J Pharmacol Toxicol Methods ; 70(1): 106-11, 2014.
Article in English | MEDLINE | ID: mdl-24929057

ABSTRACT

INTRODUCTION: A simple, reliable procedure was developed to measure binding of pyrethroid insecticides to total proteins and lipoproteins of rat and human plasma. METHODS: The extent of binding of (14)C-labeled deltamethrin (DLM), cis-permethrin (CIS) and trans-permethrin (TRANS) was quantified by a 3-step organic solvent extraction technique. Rat and human plasma samples, containing NaF to inhibit esterases, were spiked with a range of concentrations of each radiolabeled pyrethroid. Protein binding reached equilibrium within ~1h of incubation at 37°C. The samples were extracted in turn with: isooctane to collect the unbound fraction; 2-octanol to extract the lipoprotein-bound fraction; and acetonitrile to obtain the protein-bound fraction. RESULTS: Absolute recoveries of DLM, CIS and TRANS ranged from 86 to 95%. Adherence of these very lipophilic chemicals to glass and plastic was minimized by using silanized glass vials and LoBind® plastic pipettes. The method's ability to distinguish lipoprotein from protein binding was confirmed by experiments with diazepam and cyclosporine, drugs that bind selectively to albumin and lipoproteins, respectively. DISCUSSION: This procedure was effectively utilized for studies of the species-dependence of plasma protein and lipoprotein binding of three pyrethroids for inclusion in physiologically-based pharmacokinetic models of pyrethroids for use in health risk assessments of the insecticides in children and adults.


Subject(s)
Blood Proteins/chemistry , Lipoproteins/blood , Lipoproteins/chemistry , Plasma/chemistry , Pyrethrins/blood , Pyrethrins/chemistry , Radioligand Assay/methods , Animals , Carbon Radioisotopes/blood , Cyclosporine/chemistry , Diazepam/chemistry , Humans , Insecticides/blood , Insecticides/chemistry , Nitriles/blood , Nitriles/chemistry , Octanols/chemistry , Permethrin/blood , Permethrin/chemistry , Protein Binding , Rats , Risk Assessment
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