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Alterations in Autonomic Function in the Guinea Pig Eye Following Exposure to Dichlorvos Vapor

Published on Oct 1, 2008in Journal of Ocular Pharmacology and Therapeutics1.792
· DOI :10.1089/jop.2008.0020
James T. Taylor9
Estimated H-index: 9
,
Emily A. Davis4
Estimated H-index: 4
+ 3 AuthorsRobert J. Mioduszewski13
Estimated H-index: 13
Abstract
The present study investigated the effect of the organophosphate, dichlorvos (DDVP), on ocular function and cholinesterase activity in guinea pigs, using a single-animal-head-only vapor exposure system. All animals exhibited signs of mild organophosphate poisoning (e.g., salivation, chewing, lacrimation, urination, defecation, and rhinorhea) after the 20-min exposure, regardless of the DDVP exposure concentration (e.g., 35 mg/m3, 55 mg/m3, and 75 mg/m3). Pupil constriction or miosis was the most pronounced effect seen after vapor exposure. The postexposure pupil size for the 35 mg/m3 group was 45.8 ± 3.68% of the preexposure baseline measurement. Postexposure pupil size in the 55- (38 ± 1.36%) and 75 mg/m3 (38.1 ± 1.72%) groups was significantly less than both the preexposure baseline level and the 35 mg/m3 group. All groups exhibited enhanced an pupillary response to light after DDVP exposure. The enhanced light response remained even after recovery from miosis (∼1 h after exposure). Measurement of choli...
  • References (21)
  • Citations (3)
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References21
Newest
#1Paul A. Dabisch (Edgewood Chemical Biological Center)H-Index: 10
#2Michael S. Horsmon (Edgewood Chemical Biological Center)H-Index: 3
Last. Sandra A. Thomson (Edgewood Chemical Biological Center)H-Index: 13
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In the eye, it has been previously reported that exposure to a cholinesterase inhibitor results in a reduced miotic response following prolonged exposure and a decreased miotic response to the cholinergic agonists. However, no studies exist that characterize the effect of a single low-level vapor exposure to a nerve agent on parasympathetic function in the eye or determine the threshold dose for such an effect. The present study investigated the hypotheses that a single low-level exposure to som...
16 CitationsSource
#1Paul A. Dabisch (Edgewood Chemical Biological Center)H-Index: 10
#2Filip To (MSU: Mississippi State University)H-Index: 9
Last. Robert J. Mioduszewski (Edgewood Chemical Biological Center)H-Index: 13
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Several studies in conscious animals have reported parasympathetic dysfunction in the eyes following exposure to cholinesterase inhibitors. Given the similarities between the autonomic innervation in the eye and the heart, it is possible that parasympathetic dysfunction could also occur in the heart. Therefore, the present study assessed time domain indices of heart rate variability in conscious rats surgically implanted with telemetric transmitters to investigate the hypothesis that multiple ex...
10 CitationsSource
#1Nobuo YanagisawaH-Index: 43
#2Hiroshi Morita (Shinshu University)H-Index: 33
Last. T. Nakajima (Nagoya University)H-Index: 1
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Two terrorist attacks with the nerve agent Sarin affected citizens in Matsumoto and Tokyo, Japan in 1994 and 1995, killing 19 and injuring more the 6000. Sarin, a very potent organophosphate nerve agent, inhibits acetylcholinesterase (AchE) activity within the central, peripheral, and autonomic nervous systems. Acute and long-term Sarin effects upon humans were well documented in these two events. Sarin gas inhalation caused instantaneous death by respiratory arrest in 4 victims in Matsumoto. In...
189 CitationsSource
#1Paul A. DabischH-Index: 10
#1Paul A. Dabisch (NAS: National Academy of Sciences)H-Index: 2
Last. Sandra A. ThomsonH-Index: 13
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O-isopropyl methylphosphonofluoridate, also known as sarin or GB, is a highly toxic organophosphorous compound that exerts its effect by inhibiting the enzyme acetylcholinesterase. While the effects of a single exposure to GB vapor are well characterized, the effects of multiple exposures to GB vapor are less clear. Previous studies in the rat and guinea pig have demonstrated that multiple exposuresresultintolerancetothemioticeffectofnerveagents.The aim of the present study was to examine potent...
11 CitationsSource
Inhibition of acetylcholinesterase (AChE) by the organophosphorous compound sarin (GB) results in the accumulation of acetylcholine and excessive cholinergic stimulation. There are few data in the literature regarding the effects of multiple low-level exposures to GB and other organophosphorous compounds via relevant routes of exposure. Therefore, the present study was undertaken, and is the first, to investigate the effect of low-level repeated whole-body inhalation exposures to GB vapor on pup...
21 CitationsSource
#1M. Dütsch (FAU: University of Erlangen-Nuremberg)H-Index: 16
#2Harald Marthol (FAU: University of Erlangen-Nuremberg)H-Index: 18
Last. Max J. Hilz (FAU: University of Erlangen-Nuremberg)H-Index: 29
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Abstract Although diabetic autonomic neuropathy involves most organs, diagnosis is largely based on cardiovascular tests. Light reflex pupillography (LRP) non-invasively evaluates pupillary autonomic function. We tested whether LRP demonstrates autonomic pupillary dysfunction in diabetics independently from cardiac autonomic neuropathy (CAN) or peripheral neuropathy (PN). In 36 type-II diabetics (39–84 years) and 36 controls (35–78 years), we performed LRP. We determined diameter (PD), early and...
43 CitationsSource
#1F. Kamel (NIH: National Institutes of Health)H-Index: 12
#2William K. Boyes (EPA: United States Environmental Protection Agency)H-Index: 28
Last. D P Sandler (NIH: National Institutes of Health)H-Index: 4
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Background Retinal degeneration is the leading cause of visual impairment in older adults, but little is known about its relationship to neurotoxic exposures. Methods The Agricultural Health Study is a cohort study of licensed pesticide applicators from Iowa and North Carolina. We used cross-sectional data from self-administered questionnaires given at enrollment in 1994–1996 to compare pesticide use in 154 applicators who reported retinal degeneration and 17,804 controls. Results Retinal degene...
36 CitationsSource
#1John M. RingmanH-Index: 37
#2Jeffrey L. Cummings (UCLA: University of California, Los Angeles)H-Index: 138
Objective: To review preclinical and clinical studies of metrifonate, a cholinesterase inhibitor relevant to the treatment of Alzheimer's disease. Data Sources: English-language literature identified by MEDLINE using the term metrifonate was reviewed, and bibliography-sorted searches were conducted. Study Findings: Metrifonate is an organophosphate cholinesterase inhibitor effective in the treatment of the cognitive symptoms of Alzheimer's disease and currently under review by the U.S. Food and ...
32 CitationsSource
#1Bradley R. Williams (SC: University of Southern California)H-Index: 10
The pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of metrifonate, a long-acting cholinesterase inhibitor, are discussed. Attempts to correct the central cholinergic deficits associated with Alzheimer's disease have included administration of cholinergic precursors, cholinergic agonists, and cholinesterase inhibitors. To date, two reversible cholinesterase inhibitors-tacrine and donepezil-have been marketed. Metrifonate, an organophosphate, is converted nonenzymatically t...
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#1Volker HinzH-Index: 11
#2Sonja GrewigH-Index: 1
Last. Bernard SchmidtH-Index: 16
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Metrifonate, a long-acting cholinesterase (ChE) inhibitor with very low toxicity in warm-blooded animals, inhibits rat brain and serum cholinesterase (ChE) in vitro through its hydrolytic degradation product, dichlorvos. This conclusion is based on the finding that metrifonate-induced ChE inhibition showed the same pH dependence as its reported dehydrochlorination to dichlorvos. The ChE inhibition induced by dichlorvos was not pH dependent. It was mediated by a competitive drug interaction with ...
44 CitationsSource
Cited By3
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#1Charlotte A. Hall (University of Hertfordshire)H-Index: 4
#2Robert P. Chilcott (University of Hertfordshire)H-Index: 21
The pupillary light reflex (PLR) describes the constriction and subsequent dilation of the pupil in response to light as a result of the antagonistic actions of the iris sphincter and dilator muscles. Since these muscles are innervated by the parasympathetic and sympathetic nervous systems, respectively, different parameters of the PLR can be used as indicators for either sympathetic or parasympathetic modulation. Thus, the PLR provides an important metric of autonomic nervous system function th...
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#1Lily Y. L. ChangH-Index: 3
#2Jason Turuwhenua (University of Auckland)H-Index: 7
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Clinical assessment of pupil appearance and pupillary light reflex (PLR) may inform us the integrity of the autonomic nervous system (ANS). Current clinical pupil assessment is limited to qualitative examination, and relies on clinical judgment. Infrared (IR) video pupillography combined with image processing software offer the possibility of recording quantitative parameters. In this study we describe an IR video pupillography set-up intended for human and animal testing. As part of the validat...
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#1Youchi Zhang (CAS: Chinese Academy of Sciences)
#1Yun Zhang (CAS: Chinese Academy of Sciences)H-Index: 21
Last. Wensui Luo (CAS: Chinese Academy of Sciences)
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