• Proceedings of the PSK Conference
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• 2003.04a
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• pp.259.3-260
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• 2003

Alzheimer's disease(AD) is the most common cause of senile dementia in elderly people and the causes of AD are currently not fully understood. However, AD is generally understood to be associated with reduced levels of acetylcholine in the brain as cholinergic neurons are lost and cholinergic neurotransmission declines. There are growing evidences that two types of cholinesterase(ChE), i.e., acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) both play important roles in the regulation of acetylcholine level in brain and thus may have a crucial role in the development and progression of AD. (omitted)

• Journal of Society of Preventive Korean Medicine
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• v.15 no.3
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• pp.39-49
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• 2011

Objectives : Vascular dementia is the second common cause of dementia after Alzheimer's disease. It assumed that the ratio of prescription drugs on vascular dementia are quite different from each hospital in Western medicine or Oriental medicine, respectively. The aim of this research is to collect and analyze the ratio of prescription drugs on vascular dementia in Western medicine or Oriental medicine in university hospitals. Methods : We collected and analyzed the data related to prescriptions on vascular dementia in the department of neurology in three university hospitals(A, B, C) and in the department of internal medicine in two Oriental medicine hospitals(Daegu Haany Oriental Hospital, Dong Eui Oriental Hospital). Results : In the department of neurology in A university hospital, donepezil(69.1%), memantine(14.0%), rivastigmine(12.3%), galantamine(4.5%) were prescribed in order. In B university hospital, galantamine(57.8%) donepezil(33.3%), rivastigmine(6.7%), donepezil with memantine(4.4%) were prescribed. In C university hospital, donepezil(62.0%), rivastigmine(25.0%), galantamine(7.0%) memantine(6.0%) were prescribed. The average frequencies of prescribed medication in the department of neurology in A, B, C university hospitals were donepezil(54.8%), galantamine(23.1%), rivastigmine(14.7%), memantine(7.4%). In Oriental medicine hospitals, various prescriptions have been used for vascular dementia. Among them, Ansincheongnoetang (安神淸腦湯) and Gamijihangeumja(加味地黃飮子) were often prescribed in Daegu Haany Oriental Hospital, and Bojungikgitang(補中益氣湯) in Dong Eui Oriental Hospital, too. Conclusions : Cholinesterase inhibitors such as donepezil, galantamine, rivastigmine and NMDA receptor inhibitor like memantine have been used as a drug of choice for vascular dementia in all surveyed university hospitals. In oriental hospitals, various prescriptions have been used for vascular dementia.

• Journal of the Korea Institute of Military Science and Technology
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• v.16 no.2
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• pp.218-224
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• 2013

Organophosphorus compounds are irreversible inhibitors of cholinesterase enzyme. Exposure causes a progression of toxic signs, including hypersecretion, tremor, convulsion, respiratory distress, epileptiform seizure, brain injuries and death. To protect brain injuries, administration of diazepam as a neuroprotectant is now considered essential for severely exposed nerve agent casualties. However, studies have shown diazepam to provide less than total protection against the neuropathological consequences of nerve agent exposure. In this context, extensive studies have been carried out to find out effective alternative drugs to protect brain from epileptiform seizures induced by organophosphate compounds intoxication. It has been reported that a combination of carbamate and anticholinergic or antiglutamatergic can be a very effective medical countermeasure in dealing with the threat of organophosphorous poisoning. In this study, experimental animals including rats and guinea pigs were implanted with microelectrodes on their brain sculls, and treated with various centrally acting drugs such as physostigmine and procyclidine prior to soman challenge, and then its electroencephalography(ECoG) was monitored to see anticonvulsant effects of the drugs. It was found that seizure activities in ECoG were not always in proportion to clinical signs induced by soman intoxication, and that combinative pretreatment with physostigmine plus procyclidine effectively stopped the seizures induced by organophosphorous poisoning.

• Bulletin of the Korean Chemical Society
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• v.32 no.8
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• pp.2593-2598
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• 2011

Polyphenols (PPs) are known as antioxidant compounds having benign biological activities. In this paper, a series of hybrid molecules between the free or acetyl protected polyphenol compounds were synthesized and their in vitro antioxidant activity (DPPH assay) and cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibition activities were evaluated. As expected, free phenolic hybrid compounds (6 and 8) showed better antioxidant activity than acetyl protected hybrid compounds (5 and 7) from DPPH assay. But the contrast result was obtained from BuChE inhibition assay. Acetyl protected hybrid compounds (5 and 7) showed better inhibition activity for BuChE than free phenolic hybrid compounds (6 and 8). Specifically, 10 (AcFA-AcFA) were shown as an effective inhibitor of BuChE ($IC_{50}=2.3{\pm}0.3{\mu}M$) and also had a great selectivity for BuChE over AChE (more than 170 fold). Inhibition kinetic studies with acetyl protected compounds (5, 7, 9, and 10) indicated that 5, 7 and 10 are a hyperbolic mixed-type inhibition and 10 is a competitive inhibition type. The binding affinity (Ki) value of 10 to BuChE is $2.32{\pm}0.15{\mu}M$.

• Korean Journal of Veterinary Research
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• v.48 no.2
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• pp.131-137
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• 2008

Pesticides are extensively used for the control of crop pests in agriculture and forestry. Organophosphate (OP) and carbamate pesticides are especially effective for the control of a variety of harmful insects. However, these cholinesterase inhibitors are also dangerous to non-target organisms (wildlife and other animals) because of their high acute toxicity. Most poisonings by pesticides occur as a result of misuse or accidental exposure, but intentional killing of unwanted animals also occurs. At the request of a local autonomous entity, we investigated wild bird poisonings by pesticides from 2003 to 2007. The 207 suspicious samples of pesticide poisoning based on the necropsy were analyzed by GC/NPD, GC/FPD, or GC/MSD. We looked for trends in the identification of pesticides in wild birds thought to have died from poisoning. Pesticides were determined in 59% of the total samples analyzed. Phosphamidon and monochrotophos were the most common pesticides identified, which amounted to 77% of the subtotal. Other OP and carbamate pesticides were also found in various concentrations from dead wild birds. The determined rates of pesticides were as high as 86% and 76% in 2003 and 2006, respectively, during an outbreak of avian influenza in Korea.

• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1025-1029
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• 2013

In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between ${\alpha}$-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The $IC_{50}$ values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE ($IC_{50}=0.44{\pm}0.24{\mu}M$). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is $4.3{\pm}0.09{\mu}M$.

• IMMUNE NETWORK
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• v.21 no.5
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• pp.35.1-35.16
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• 2021

Gulf War Veterans' Illnesses (GWI) encompasses a broad range of unexplained symptomology specific to Veterans of the Persian Gulf War. Gastrointestinal (GI) distress is prominent in veterans with GWI and often presents as irritable bowel syndrome (IBS). Neurotoxins, including organophosphorus pesticides and sarin gas, are believed to have contributed to the development of GWI, at least in a subset of Veterans. However, the effects of such agents have not been extensively studied for their potential impact to GI disorders and immunological stability. Here we utilized an established murine model of GWI to investigate deleterious effects of diisopropyl fluorophosphate (DFP) exposure on the mucosal epithelium in vivo and in vitro. In vivo, acute DFP exposure negatively impacts the mucosal epithelium by reducing tight junction proteins and antimicrobial peptides as well as altering intestinal microbiome composition. Furthermore, DFP treatment reduced the expression of IL-17 in the colonic epithelium. Conversely, both IL-17 and IL-17C treatment could combat the negative effects of DFP and other cholinesterase inhibitors in murine intestinal organoid cells. Our findings demonstrate that acute exposure to DFP can result in rapid deterioration of mechanisms protecting the GI tract from disease. These results are relevant to suspected GWI exposures and could help explain the propensity for GI disorders in GWI Veterans.