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1.
Sci Rep ; 6: 22965, 2016 Mar 18.
Article in English | MEDLINE | ID: mdl-26987796

ABSTRACT

To determine whether a C. elegans bioassay could predict mammalian developmental activity, we selected diverse compounds known and known not to elicit such activity and measured their effect on C. elegans egg viability. 89% of compounds that reduced C. elegans egg viability also had mammalian developmental activity. Conversely only 25% of compounds found not to reduce egg viability in C. elegans were also inactive in mammals. We conclude that the C. elegans egg viability assay is an accurate positive predictor, but an inaccurate negative predictor, of mammalian developmental activity. We then evaluated C. elegans as a tool to identify mechanisms affecting toxicological outcomes among related compounds. The difference in developmental activity of structurally related fungicides in C. elegans correlated with their rate of metabolism. Knockdown of the cytochrome P450s cyp-35A3 and cyp-35A4 increased the toxicity to C. elegans of the least developmentally active compounds to the level of the most developmentally active. This indicated that these P450s were involved in the greater rate of metabolism of the less toxic of these compounds. We conclude that C. elegans based approaches can predict mammalian developmental activity and can yield plausible hypotheses for factors affecting the biological potency of compounds in mammals.


Subject(s)
Caenorhabditis elegans/drug effects , Cytochrome P-450 Enzyme System/genetics , Mammals/growth & development , Pesticides/toxicity , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/growth & development , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Cytochrome P-450 Enzyme System/metabolism , Gene Knockout Techniques , Humans , Mammals/metabolism , Models, Animal , Pesticides/chemistry , Pesticides/pharmacology , Structure-Activity Relationship , Toxicity Tests
2.
Cochlear Implants Int ; 11 Suppl 1: 15-28, 2010 Jun.
Article in English | MEDLINE | ID: mdl-21756581

ABSTRACT

Recently, the evaluation of the role of the central auditory system in the utilization of cochlear implants has received much attention. In order to fully understand the results of cochlear implantation, one must have an understanding of how the brain is influenced by electrical stimulation of the auditory nerve. This review provides an overview of the structure and function of the central auditory nervous system and the changes that occur as a result of cochlear implant use. Evidence of central auditory plasticity is discussed highlighting key imaging and evoked potential studies.


Subject(s)
Adaptation, Physiological , Auditory Cortex/physiology , Cochlear Implantation , Cochlear Nerve/physiopathology , Evoked Potentials, Auditory, Brain Stem/physiology , Adolescent , Age Factors , Child , Child, Preschool , Cochlear Implants , Deafness/etiology , Deafness/physiopathology , Deafness/surgery , Electric Stimulation , Female , Follow-Up Studies , Humans , Male , Risk Assessment , Time Factors , Treatment Outcome
3.
J Am Acad Audiol ; 20(9): 569-81; quiz 590-1, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19902704

ABSTRACT

BACKGROUND: Use of a competition stimuli (e.g., video) in clinical settings is a widespread practice, yet the effects of these stimuli on evoked potentials are not well understood. PURPOSE: The present investigation acquired the click evoked auditory N1-P2 in quiet and in two types of competition: during presentation of an unrelated visual stimulus or audiovisual stimulus. Responses were acquired in each of these conditions at two click stimulus levels (i.e., 35 and 65 dBnHL) to determine if the effect of competition was greater closer to threshold. An attempt was made to quantify effect robustness by examining within- and between-session reliability. RESEARCH DESIGN: Repeated measures ANOVA. STUDY SAMPLE: 17 normal hearing female subjects. RESULTS: Findings indicated a significant effect of audiovisual competition on the amplitude of the N1-P2, and a borderline significant effect of visual competition on this index. The extent of visual competition was better conveyed when examined on a case-by-case basis, in which was revealed a subgroup of the sample that was negatively affected by visual competition. There was no interaction between competition and click stimulus level. CONCLUSIONS: Although competition stimuli can negatively affect the amplitude of the N1-P2, consideration should be given to subjects on a case-by-case basis to warrant if removal of this stimulus is necessary.


Subject(s)
Acoustic Stimulation , Auditory Perception/physiology , Evoked Potentials, Auditory , Photic Stimulation , Female , Humans , Reproducibility of Results , Young Adult
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