Abstract:
:Cholinesterases (ChEs) are classified as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) according to their substrate specificity and sensitivity to selected inhibitors. The activities of AChE in red blood cells (RBC-AChE) and BChE in serum can be used as potential biomarkers of suppressed and/or heightened activity in the central and peripheral nervous systems. Exposure to organophosphate (OP) chemical warfare agents (CWAs), pesticides, anesthetics, and a variety of drugs such as cocaine, as well as some neurodegenerative and liver disease states, selectively reduces AChE or BChE activity. In humans, the toxicity of pesticides is well documented. Therefore, blood cholinesterase activity can be exploited as a tool for confirming exposure to these agents and possible treatments. Current assays for measurement of RBC-AChE and serum BChE require several labor-intensive processing steps, suffer from wide statistical variation, and there is no inter-laboratory conversion between methods. These methods, which determine only the serum BChE or RBC-AChE but not both, include the Ellman, radiometric, and deltapH (modified Michel) methods. In contrast, the Walter Reed Army Institute of Research Whole Blood (WRAIR WB, US Patent #6,746,850) cholinesterase assay rapidly determines the activity of both AChE and BChE in unprocessed (uncentrifuged) whole blood, uses a minimally invasive blood sampling technique (e.g., blood from a finger prick), and is semi-automated for high-throughput using the Biomek 2000 robotic system. To date, the WRAIR whole blood assay was used to measure AChE and BChE activities in human blood from volunteers in FDA clinical trials. In the first FDA study, 24 human subjects were given either 30 mg PB orally (n = 19) or placebo (n = 5). Blood samples were obtained pre-dosing and 2.5, 5, 8, and 24 h post-dosing. The samples were analyzed for AChE and BChE activity using the WRAIR WB robotic system, and for PB concentration by HPLC. We found that maximal inhibition of AChE (26.2%) and concentration of PB (17.1 ng/mL) occurred at 2.5 h post-PB dosing. AChE activity returned to almost 100% of pre-dose values by 6 h. A dose-dependent linear correlation was found between the amount of PB measured in the blood and the inhibition of AChE. Following soman (GD) exposure, recovered AChE activity was similar to levels that were reversibly protected by the PB administration. Therefore, the WRAIR ChE WB data clearly supports the conclusion that PB is an effective pre-treatment drug for nerve agent exposure (GD). In the second FDA human study for the treatment of Alzheimer's disease, the WRAIR ChE WB assay was used to determine the RBC-AChE and serum BChE profile of healthy elderly volunteers receiving Huperzine A. Huperzine A is a plant-derived reversible and selective AChE inhibitor compared to BChE, and is a more potent inhibitor of AChE than PB. Huperzine A is available as a nutraceutical, a natural supplement reported to improve memory, and has a variety of neuroprotective effects. Individuals received an increasing dose regimen of huperzine A (final dose 200 microg after 4 weeks), which produced more than 50% inhibition of RBC-AChE. Huperzine A was well tolerated by these patients at doses that sequestered more RBC-AChE than PB, and thus warrants further study as a prophylaxis for OP poisoning in addition to Alzheimer's therapy. Due to the documented use of OPs by terrorists and in warfare around the globe, Federal, State, and local authorities need a reliable, fast, inexpensive, and standard method for confirming such an assault in order to initiate appropriate containment, decontamination, and treatment measures. This assay is ideal for prescreening military personnel for atypical ChE activities that would preclude their deployment to areas of potential CWA exposure. The WRAIR WB ChE assay will fulfill the requirement for rapid and reliable monitoring of such exposure in military and civilian populations.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Gordon RK,Haigh JR,Garcia GE,Feaster SR,Riel MA,Lenz DE,Aisen PS,Doctor BPdoi
10.1016/j.cbi.2005.10.031subject
Has Abstractpub_date
2005-12-15 00:00:00pages
239-46eissn
0009-2797issn
1872-7786pii
S0009-2797(05)00272-3journal_volume
157-158pub_type
杂志文章abstract::Caffeine was found to potentiate the cytotoxic effect of misonidazole (1-(2-nitroimidazol-1-yl)-3-methoxy-2-propanol) towards mammalian cells in vitro. This enhancement of toxicity is shown to occur under both aerobic and hypoxic conditions. Split dose experiments indicate that the general shape of the hypoxic surviva...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(82)90089-8
更新日期:1982-08-01 00:00:00
abstract::Benzene-induced hematopoietic toxicity is an aryl hydrocarbon receptor (AhR)-related adverse effect that is not exhibited in AhR-knockout (KO) mice. In the hematopoietic system, the steady-state expression of AhRs is limited in the hematopoietic progenitor cells; thus, a hierarchical hematopoietic impairment starts fr...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2009.12.022
更新日期:2010-03-19 00:00:00
abstract::Mitochondrial dysfunction appears to contribute to some of the loss of function accompanying ageing. Mitochondria from aged tissue use oxygen inefficiently impairing ATP synthesis and results in increased oxidant production. A high flux of oxidants not only damages mitochondria, but other important cell biomolecules a...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(01)00268-x
更新日期:2001-11-28 00:00:00
abstract::Isolated rat hepatocytes were used to investigate the biochemical mechanisms of toxicity of triethyllead (Et3Pb+), a highly neurotoxic degradation product of the antiknocking petrol additive tetraethyllead. As early as 5 min from the addition of 50 microM Et3Pb+ to hepatocyte suspensions a decrease of mitochondrial me...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(94)90111-2
更新日期:1994-01-01 00:00:00
abstract::Keeping in mind the vasodilator action of prostaglandins, the control that they exercise over the vascular supply of kidneys and the sympathetic activity, research was conducted in order to establish the effect of arachidonic acid, the precursor of PGE2, on experimental hypertension in the rat. The experimental hypert...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(75)90087-3
更新日期:1975-04-01 00:00:00
abstract::The present study investigated the protective efficacy of dl-alpha-lipoic acid (LA) on adriamycin (ADR)-induced oxidative damage in rat testis. Adult male albino rats of Wistar strain were administered ADR (1 mg/kg body weight, i.v.), once a week for 10 weeks. ADR injected rats showed increased oxidative stress with a...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2005.12.007
更新日期:2006-03-25 00:00:00
abstract::A model is presented which correlates the survival of normal human fibroblasts (NF) after exposure to N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) with the rate of excision of carcinogen residues bound to DNA. Measurements of the rate of excision of carcinogen residues suggest that this is a first-order process with 37...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(82)90005-9
更新日期:1982-03-01 00:00:00
abstract::The Nuclear Factor-kappa B (NF-κB) pathway is vital for immune system regulation and pro-inflammatory signaling. Many inflammatory disorders and diseases, including cancer, are linked to dysregulation of NF-κB signaling. When macrophages recognize the presence of a pathogen, the signaling pathway is activated, resulti...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2017.12.019
更新日期:2018-01-25 00:00:00
abstract::The 2 pH dependent peaks formed in the Soret region by the treatment of reduced hepatic microsomes or purified cytochrome P-448 with ethyl isocyanide do not exhibit identical dependence on ethyl isocyanide concentration. This behavior and other facts regarding double Soret spectra can be explained by a simple expostul...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(78)90051-0
更新日期:1978-02-01 00:00:00
abstract::Thalidomide has anti-inflammatory, immunomodulatory, and anti-angiogenic properties. It has been used to treat a variety of cancers and autoimmune diseases. This study aimed to characterize anti-inflammatory activities of novel thalidomide analogs by exploring their effects on splenocytes proliferation and macrophage ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2015.05.017
更新日期:2015-08-05 00:00:00
abstract::Organophosphorus compounds (OP), which mainly penetrate via the percutaneous pathway, represent a threat for both military and civilians. Body surface decontamination is vital to prevent victims poisoning. The development of a cost-effective formulation, which could be efficient and easy to handle in case of mass cont...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2016.04.035
更新日期:2017-04-01 00:00:00
abstract::Human foreskin cell cultures in scheduled DNA synthesis (S phase) of the cell cycle were exposed to UV irradiation at a dose of 10 J . m-1 in the presence of insulin. These treated cell populations, when selectively passaged in a high amino acid supplemented complete growth medium (CM) after 20 Dulbecco's phosphate bu...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(81)90028-4
更新日期:1981-07-01 00:00:00
abstract::This study investigated the effect of inducers on the major enzymes responsible for metabolising the quinone antitumor agent mitoxantrone, and on its cytotoxicity in MCF 7 human breast cancer cells. Four inducers were used: 1,2-benzanthracene (BA), phenobarbitone (PB); rifampicin (R) and dexamethasone (DEX). Of these,...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(94)03603-6
更新日期:1995-07-14 00:00:00
abstract::Nephrotoxicity is a major adverse effect of chromium poisoning. In the present study, we investigated the potential renoprotective effect and underlying mechanisms of carvedilol, a non-specific β-adrenergic blocker using rat model of potassium dichromate-induced nephrotoxicity. Rats were pretreated with carvedilol (10...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2014.09.009
更新日期:2014-11-05 00:00:00
abstract::The polycyclic aromatic hydrocarbon (PAH) benzo[ghi]perylene (BghiP) lacks a "classic" bay-region and is therefore unable to form vicinal dihydrodiol epoxides thought to be responsible for the genotoxicity of carcinogenic PAHs like benzo[a]pyrene. The bacterial mutagenicity of BghiP increases considerably after inhibi...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2008.07.010
更新日期:2008-11-25 00:00:00
abstract::The atypical butyrylcholinesterase (aBuChE) from Oryzias latipes shares approximately 65% sequence similarity to both acetylcholinesterase and butyrylcholinesterase and was studied for its capacity to spontaneously reactivate following inhibition by organophosphorus nerve agents. Like other cholinesterases, aBuChE was...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2016.03.016
更新日期:2016-11-25 00:00:00
abstract::The neuropathologic mechanisms after exposure to lethal doses of nerve agent are complex and involve multiple biochemical pathways. Effective treatment requires drugs that can simultaneously protect by reversible binding to the acetylcholinesterase (AChE) and blocking cascades of seizure related brain damage, inflamma...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2012.10.016
更新日期:2013-03-25 00:00:00
abstract::MicroRNAs (miRNAs) have been regarded as potential modulators in varying ocular diseases, including age-related cataract (ARC). However, the roles of miR-221 in ARC progression and its underlying mechanism remain poorly understood. In this study, human lens epithelial cell line (SRA01/04) was used to investigate the p...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2019.03.021
更新日期:2019-06-01 00:00:00
abstract::tert-Butylhydroquinone (BHQ), an antioxidant used as a food additive, exhibits an anticancer effect at low doses, but is carcinogenic in rodents at high doses. BHQ is metabolized into cytotoxic tert-butylquinone (TBQ), which is further converted to 6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one (TBEH) through 6-t...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2014.09.023
更新日期:2015-06-05 00:00:00
abstract::Alkyl adducts at the O6-position of guanine constitute promutagenic DNA lesions likely to be involved in the initiation of malignant transformation. They can be removed by a cellular acceptor protein termed O6-alkylguanine-DNA alkyltransferase (AT). In rat liver this repair enzyme can be induced by a variety of hepato...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(86)90060-8
更新日期:1986-12-01 00:00:00
abstract::Inhibition of CYP enzymes is thought to be the most common cause of drug-drug and/or herb-drug interactions. To characterize the inhibition of CYP enzymes activities by chemicals, enzyme inhibition kinetic experiments are usually carried out. The purpose of this letter is to call attention to evaluate the enzyme inhib...
journal_title:Chemico-biological interactions
pub_type: 评论,信件
doi:10.1016/j.cbi.2014.10.010
更新日期:2014-10-05 00:00:00
abstract::Chronic exposure of humans to benzene causes severe bone marrow cell depression leading to aplastic anemia. Marrow stromal macrophage dysfunction and deficient interleukin-1 production has been reported for patients with severe aplastic anemia. The stromal macrophage, a target of benzene toxicity, is involved in hemat...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(95)03647-4
更新日期:1995-12-22 00:00:00
abstract::Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases, and the risk of developing OA significantly increases with age as well as with concomitant diseases, such as diabetes. Advanced glycation end products (AGEs) accumulate in the body over time and are associated with increased expression of va...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.108968
更新日期:2020-05-01 00:00:00
abstract::The dietary exposure of rats to cadmium (75 ppm) for periods of up to 48 weeks caused an accumulation of cadmium in the femur, and an inhibition of the accumulation of zinc in the bone. After 48 weeks of cadmium treatment, there was a decreased activity of alkaline phosphatase in the femur. This effect was prevented b...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(80)90155-6
更新日期:1980-03-01 00:00:00
abstract::Liver alcohol dehydrogenase (E.C.1.1.1.1) is an NAD(+)/NADH dependent enzyme with a broad substrate specificity being active on an assortment of primary and secondary alcohols. It catalyzes the reversible oxidation of a wide variety of alcohols to the corresponding aldehydes and ketones as well as the oxidation of cer...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(00)00263-5
更新日期:2001-01-30 00:00:00
abstract::We are investigating treatments for cocaine abuse based on viral gene transfer of a cocaine hydrolase (CocH) derived from human butyrylcholinesterase, which can reduce cocaine-stimulated locomotion and cocaine-primed reinstatement of drug-seeking behavior in rats for many months. Here, in mice, we explored the possibi...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2012.08.015
更新日期:2013-03-25 00:00:00
abstract::In isolated frog heart it was established that methylene-blue (MB, an oxidizing agent) decreased, while ascorbate (ASC, a reducing agent) increased the frequency of autorhythmic heart contractions. After MB treatment, in parallel with this phenomenon, the extracellular K+ concentration [K+]o showed a slow increase, bu...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(87)90092-5
更新日期:1987-01-01 00:00:00
abstract::Pineal hormone melatonin is an important regulator of endocrine and circadian rhythms in vertebrates. Since liver is assumed to be the major organ in the metabolism of this indole hormone, we investigated the effect of the known Ah-receptor agonist, 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) on melatonin metabolism i...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(00)00153-8
更新日期:2000-06-01 00:00:00
abstract::Recombinant (r) and native butyrylcholinesterse (BChE) are potent bioscavengers of organophosphates (OPs) such as nerve agents and pesticides and are undergoing development as antidotal treatments for OP-induced toxicity. Because of the lethal properties of such agents, regulatory approval will require extensive testi...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2015.09.021
更新日期:2015-12-05 00:00:00
abstract::The stereospecific 5β-reduction of Δ(4)-3-ketosterols is very difficult to achieve chemically and introduces a 90° bend between ring A and B of the planar steroid. In mammals, the reaction is catalyzed by steroid 5β-reductase, a member of the aldo-keto reductase (AKR) family. The human enzyme, AKR1D1, plays an essenti...
journal_title:Chemico-biological interactions
pub_type: 杂志文章,meta分析
doi:10.1016/j.cbi.2010.12.020
更新日期:2011-05-30 00:00:00