Publications by authors named "Catherine A White"

Varicella zoster virus (VZV) establishes lifelong infection after primary disease and can reactivate. Several drugs are approved to treat VZV diseases, but new antivirals with greater potency are needed. Previously, we identified β-l-5-((-2-bromovinyl)-1-((2,4)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl))uracil (l-BHDU, ), which had significant anti-VZV activity.

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Permethrin exposure of children and adults is widespread in many populations, but knowledge of its relative toxicokinetics (TK) and health risks in immature age groups is lacking. Studies were conducted in rats to determine the influence of immaturity and sex (on plasma and target organ dosimetry of each of the insecticide's 2 isomers, cis- and trans-permethrin [CIS and TRANS]). Postnatal day 15, 21, and 90 (adult), Sprague Dawley rats were orally administered a graduated series of doses of CIS and TRANS in corn oil.

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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.

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An in vitro to in vivo (IVIVE) extrapolation based-physiologically based pharmacokinetic (PBPK) modeling approach was demonstrated to understand age-related differences in kinetics and how they potentially affect age-related differences in acute neurotoxic effects of pyrethroids. To describe the age-dependent changes in pyrethroid kinetics, it was critical to incorporate age-dependent changes in metabolism into the model. As such, in vitro metabolism data were collected for 3 selected pyrethroids, deltamethrin (DLM), cis-permethrin, and trans-permethrin, using liver microsomes and cytosol, and plasma prepared from immature and adult rats.

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Permethrin (PER), a type I pyrethroid, is the most widely used insecticide in domestic settings in the United States. The overall objective of this study was to assess the efficiency of the blood-brain barrier (BBB) as an obstacle to the C--permethrin (CIS) and C--permethrin (TRANS) isomers of PER, and to determine whether its barrier function changes during maturation of the rat. Experiments were conducted to quantify brain uptake of CIS and TRANS in postnatal day 145, 21, and 90 Sprague-Dawley rats.

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Trichloroethylene (TCE) and 1,1,1-trichloroethane (TRI) are frequent contaminants of drinking water and of groundwater at hazardous waste sites. There is relatively little information on the target organ deposition of TRI, despite its ingestion and common occurrence in humans. An important aim of the study was to delineate and contrast the toxicokinetics (TK) and bioavailability (F) of TRI and its well metabolized congener, TCE.

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Background And Objective: Previous research has shown an effect of various psychosocial stressors on unconstrained cognitive flexibility, such as searching through a large set of potential solutions in the lexical-semantic network during verbal problem-solving. Functional magnetic resonance imaging has shown that the presence of the short (S) allele (lacking a 43-base pair repeat) of the promoter region of the gene (SLC6A4) encoding the serotonin transporter (5-HTT) protein is associated with a greater amygdalar response to emotional stimuli and a greater response to stressors. Therefore, we hypothesized that the presence of the S-allele is associated with greater stress-associated impairment in performance on an unconstrained cognitive flexibility task, anagrams.

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There is increasing concern that infants and children may be at increased risk of neurological effects of pyrethroids, the most widely used class of insecticide. The objectives of this investigation were to (1) characterize the dose-dependent toxicokinetics (TK) of deltamethrin (DLM) for exposures ranging from environmentally relevant to acutely toxic; (2) determine the influence of an aqueous versus oil vehicle on oral absorption and bioavailability; and (3) determine whether DLM exhibits low-dose, age-equivalent internal dosimetry. Serial arterial plasma samples were obtained for 72 h from adult, male Sprague Dawley rats given 0.

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Rationale: Transfluthrin is a relatively non-toxic rapid-acting synthetic pyrethroid insecticide. It is widely used in household and hygiene products. A sensitive and accurate bioanalytical method is required for quantification of its concentration in plasma and its potential target organ, the brain for studies to assess its health effects and toxicokinetics in mammals.

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A sensitive method for the simultaneous determination of cis-permethrin (cis-PERM) and trans-permethrin (trans-PERM) in small volumes (100μL) of rat plasma and brain homogenate was developed, using a liquid-liquid extraction for sample preparation and gas chromatography-negative chemical ionization mass spectrometry (GCNCI-MS) for detection. Quantitation of trace levels of the insecticide in small volumes of biological samples is essential to support toxicokinetic studies in small animals. There are currently no validated methods in the literature for determining cis-PERM and trans- PERM in volumes as low as 100μL of rat plasma or brain homogenate.

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Pyrethroids, including permethrin and deltamethrin (DLM), are very widely used of insecticides. It was hypothesized that lower plasma binding and increased blood-brain barrier (BBB) penetration of DLM in immature rats contribute to the higher brain concentrations of DLM and more pronounced neurotoxicity reported in this age group. The left brain of anesthetized adult rats was perfused for 2min via a carotid artery with 1μM C-DLM in: 2-5% human serum albumin (HSA); plasma from adult and 15- and 21-d-old rats; and plasma from human donors of: birth-1 week, 1-4 weeks, 4 weeks-1 year, 1-3 years and adults.

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Permethrin, the most widely used household insecticide in the United States, is marketed as a mixture of its cis (CIS) and trans (TRANS) isomers. The major objective of this investigation is to develop and utilize a reliable approach to determine in vivo partition coefficients (PCs) for CIS and TRANS in immature and adult Sprague-Dawley rats. Adult, postnatal day (PND) 21, and PND 15 rats were infused with environmentally relevant concentrations of CIS or TRANS via a subcutaneous osmotic pump for 48 or 72 h.

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Concern about potential susceptibilities of infants and children to chemicals has led to the consideration of immature rodents as potential test surrogates. Maturation of some hepatic microsomal cytochrome P450s (CYPs), that participate in metabolic activation of organic solvents and polycyclic aromatic hydrocarbons (PAHs), may differ significantly between humans and rodents. The present investigation was undertaken to delineate the ontogeny of selected hepatic CYPs in male and female Sprague-Dawley (S-D) rats, and to contrast them with developmental profiles in humans.

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Objective. To determine the impact of emergency preparedness simulations in mass triage and mass dispensing on student pharmacist performance and perceived competency when assuming pharmacist roles in disaster situations. Design.

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Previous pharmacokinetic studies of deltamethrin (DLM) have revealed that brain levels of this highly lipophilic pyrethroid insecticide are only 15-20% of plasma levels. Experiments were performed to assess determinants limiting CNS access including plasma protein binding and the efflux transporter, P-gp. A human brain microvascular endothelial cell line, hCMEC/D3, was utilized as a model in vitro system to evaluate blood-brain barrier (BBB) permeation.

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Natural products have provided an invaluable source of inspiration in the drug discovery pipeline. The oceans are a vast source of biological and chemical diversity. Recently, this untapped resource has been gaining attention in the search for novel structures and development of new classes of therapeutic agents.

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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.

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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.

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Objective: To compare the pharmacokinetics of a novel bioadhesive gel formulation of midazolam after intranasal (IN) administration with that of midazolam solution after IN, IV, and rectal administration to dogs.

Animals: 10 (5 males and 5 females) healthy adult Beagles.

Procedures: Dogs were assigned to 4 treatment groups for a crossover study design.

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Recent research revealed decreased access to semantic and associative networks in acute cocaine withdrawal. In autism, such behavioral outcomes are associated with decreased functional connectivity using functional magnetic resonance imaging. Therefore, we wished to determine whether connectivity is also decreased in acute cocaine withdrawal.

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The Purpose of this study was to determine the stability of an extemporaneously prepared intranasal formulation of midazolam for the treatment of status epileptus in dogs. An aqueous solution of midazolam (50mg/mL) was prepared by dissolving 500mg of midazolam powder in sterile water for injection containing carbopol (0.4%) and benzalkonium chloride (0.

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A decrease in interaction between brain regions is observed in individuals with autism spectrum disorder (ASD), which is believed to be related to restricted neural network access in ASD. Propranolol, a beta-adrenergic antagonist, has revealed benefit during performance of tasks involving flexibility of access to networks, a benefit also seen in ASD. Our goal was to determine the effect of propranolol on functional connectivity in ASD during a verbal decision making task as compared to nadolol, thereby accounting for the potential spurious fMRI effects due to peripheral hemodynamic effects of propranolol.

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The major objective of this project was to characterize the systemic disposition of the pyrethroid, deltamethrin (DLT), in immature rats, with emphasis on the age dependence of target organ (brain) dosimetry. Postnatal day (PND) 10, 21, and 40 male Sprague-Dawley rats received 0.4, 2, or 10 mg DLT/kg by gavage in glycerol formal.

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The objectives of this study were twofold: (1) to characterize the toxicokinetics and dose-dependent systemic/tissue distribution of deltamethrin (DLM) over a range of doses in adult Sprague-Dawley (S-D) rats; (2) to provide comprehensive time course blood and tissue data for development of a physiologically based toxicokinetic (PBTK) model for DLM. DLM is one of the more neurotoxic members of a relatively new and commonly used class of insecticides, the pyrethroids. Despite widespread exposure of the general population to pyrethroids, there is little basic toxicokinetic (TK) data to use in health risk assessments or in development of PBTK models.

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A simple high-performance liquid chromatography (HPLC) method has been developed and validated for the simultaneous determination of abacavir and zidovudine (AZT) in rat plasma, amniotic fluid, fetal, and placental tissues. Extraction of abacavir, AZT, and the internal standard, azidouridine (AZDU) in amniotic fluid was carried out by protein precipitation. Extraction from plasma, fetal and placental homogenates was achieved by using a salting out technique.

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