Acetylcholine is an essential neurotransmitter found throughout the nervous system. Its action on postsynaptic receptors is regulated through hydrolysis by various carboxylesterases, especially cholinesterases (ChEs)....Acetylcholine is an essential neurotransmitter found throughout the nervous system. Its action on postsynaptic receptors is regulated through hydrolysis by various carboxylesterases, especially cholinesterases (ChEs). The acute toxicity of organophosphate (OP) compounds is directly linked to their action as inhibitors of ChE. One widely used assay for evaluating ChE activity is a spectrophotometric method developed by Ellman et al. When the enzyme source is from tissues or, in particular, blood, hemoglobin displays a spectrophotometric peak at the same wave-length used to analyze cholinergic activity. This creates a substantial background that interferes with the Ellman’s assay and must be overcome in order to accurately monitor cholinesterase activity. Herein, we directly compare blood processing methods: classical method (1.67 ± 0.30 U/mL) and HemogloBindTM treatment (1.51 ± 0.17 U/mL), and clearly demonstrate that pretreatment of blood samples with HemoglobindTM is both a sufficient and rapid sample preparation method for the assessment of ChE activity using the Ellman’s method.展开更多
To determine the predictive performance of cholinesterase compared to existing prognostic models in evaluating liver function in patients with chronic hepatitis D. METHODSIn an observational, cross-sectional and retro...To determine the predictive performance of cholinesterase compared to existing prognostic models in evaluating liver function in patients with chronic hepatitis D. METHODSIn an observational, cross-sectional and retrospective study, consecutive patients with hepatitis D cirrhosis were evaluated. Demographic, clinical and laboratory parameters were recorded. Serum cholinesterase levels were correlated with existing scoring models for chronic liver disease and Liver function tests. Receiver operating characteristic (ROC) curves were constructed to find an optimal cholinesterase level predicting ascites, Child Turcotte Pugh (CTP) score ≥ 10, model for end stage liver disease (MELD) score ≥ 15, baseline-event-anticipation (BEA) score for hepatitis D ≥ 5 and the aspartate transaminase to Platelet Ratio Index (APRI) ≥ 1.5. RESULTSThis study investigated 233 patients with chronic liver disease due to hepatitis D; 192 were male, median age 42 (16-69 years). Fifty patients had ascites and 15 had encephalopathy. One hundred and sixty-seven (71.7%) were in Child class A, 52 (22.3%) in Child class B and 14 (5.0%) in class C. A MELD score of 15 or more was seen in 24 patients. Cholinesterase levels correlated well with the INR, albumin, CTP score, MELD, MELD sodium, BEA and APRI scores (P < 0.001 each). Area under the ROC curve for ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5, APRI ≥ 1.5 was 0.836, 0.966, 0.913, 0.871 and 0.825 respectively (P < 0.001 each). Cut off values of cholinesterase (IU/L) for predicting ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5 and APRI ≥ 1.5 were < 3812, < 2853, < 2829, < 4719 and < 3954 with a sensitivity of 80%, 100%, 91.67%, 82.50%, 58.0% and specificity of 81.97%, 84.79%, 87.56%, 77.06% and 55.64% respectively. CONCLUSIONSerum cholinesterase demonstrates promising correlations with serum albumin, INR and CTP, MELD, BEA and APRI scores and is predictive of liver reserves in hepatitis D cirrhosis.展开更多
The results confirmed that diazepam inhibits the cholinesterase in rat serum,red cell,corpus striatum and diaphragm in vitro,that the higher the diazepam concentration,the stronger the cholinesterase inhibition,and th...The results confirmed that diazepam inhibits the cholinesterase in rat serum,red cell,corpus striatum and diaphragm in vitro,that the higher the diazepam concentration,the stronger the cholinesterase inhibition,and that diazepam is a reversible inhibitor to acetylcholinesterase and diazepam has a stabilizing action on red cell membranes.The role of these effects of diazepam in the treatment of organic phosphate poisoning is discussed展开更多
AIM: To understand the correlation of serum cholinesterase (CHE) activity with gastric cancer and to assess their clinical significance.METHODS: The velocity method was adopted to detect the activity of serum CHE in p...AIM: To understand the correlation of serum cholinesterase (CHE) activity with gastric cancer and to assess their clinical significance.METHODS: The velocity method was adopted to detect the activity of serum CHE in patients with gastric cancer and in patients with non-malignant tumor as controls.RESULTS: The serum CHE activity in the treatment group was significantly lower than that in the control group with a very significant difference between the two groups (83.3:113.1,P = 0.0003). Age was significantly associated with the incidence of gastric caner.CONCLUSION: Serum CHE activity has a close relation with the incidence of gastric cancer.展开更多
AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secre...AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM HCI.Nizatidine,neostigmine,carbachol or famotidine was administered i.v.as a single injection. RESULTS Intravenous administration of nizatidine(3-30 mg/kg)dose-dependently increased duodenal HCO_3^- secretion,and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg.This nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility,mimicked by i.v.injection of neostigmine(0.03 mg/kg),and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin,a cyclooxygenase inhibitor,or N^G-nitro-L-arginine methyl ester,a NO synthase inhibitor.The HCO_3^- secretory response to acetylcholine(0.001 mg/kg)was significantly potentiated by the concurrent administration of nizatidine(3mg/kg,i.v.).The IC_(50)of nizatidine for AChE of rat erythrocytes was 1.4×10^(-6)M,about 12 times higher than that of neostigmine.Neither famotidine(>10^(-3)M, 30mg/kg,i.v.)nor cisapride(> 10^(-3)M, 3mg/kg,i.v.)had any influence on AChE activity or duodenal HCO_3^- secretion.Duodenal damage induced by acid perfusion(100 mM HCI for 4 h)in the presence of indomethacin was significantly prevented by nizatidine and neostigmine,at the doses that increased the HCO_3^- secretion. CONCLUSION Nizatidine stimulates duodenal HCO_3^- secretion,in both vagal-dependent and atropine-sensitive manners,and the action is associated with the anti-AChE activity of this agent.展开更多
Objective:To explore cholinesterase inhibitory and antioxidant effect of six coniferous trees(Abies bornmulleriana,Picea pungens,Juniperus communis,Cedrus libani,Taxus baccata,and Cupressus sempervirens var.horizantal...Objective:To explore cholinesterase inhibitory and antioxidant effect of six coniferous trees(Abies bornmulleriana,Picea pungens,Juniperus communis,Cedrus libani,Taxus baccata,and Cupressus sempervirens var.horizantalis).Methods:Acetone(Ace),ethyl acetate(EtOAc),and ethanol(EtOH)extracts prepared from the needles and shoots of the six coniferous trees were screened for their acetylcholinesterase(AChE)and butyrylcholinesterasc(BChE)inhibitory activity at 100μg/mL.Antioxidant activity of the extracts was tested using 2,2-diphenyl-1-picrylhydrazyl(DPPH)and N,N-dimethyl-p-phenylendiamine(DMPD)radical scavenging,nietal-chelation capacity,ferric-(FRAP)and phosphomolibdenum-reducing antioxidant power(PRAP)assays.All of the assays were performed in ELISA microplate reader.Total phenol and flavonoid amounts in the extracts were determined spectrophotometrically.Results:Among thirty-six extracts in total,the shoot-Ace extract of Cupressus sempervirens var.horizantalis exerted the highest inhibition against AChE[(54.84±2.51)%],while the needle-Ace extract of Cedrus libani was the most effective in inhibiting BChE[(67.54±0.30)%].The highest DPPH radical scavenging effect,FRAP and PRAP was observed in the shoot-Ace and EtOAc extracts from Taxus baccata.whereas all the extracts showed a variable degree of scavenging effect against DPMD radical.The shoot-EtOAc extract of Cedrus libani had the highest metalchelation capacity[(58.04±0.70)%].The shoot extracts of Taxus baccata were determined to have the richest total phenol content,which may contribute to its marked antioxidant activity.Conclusions:The conifer species screened in this study may contain cholinesterase-inhibiting and antioxidant properties,which might be useful against Alzheimer's disease.展开更多
The density functional theory at the B3LYP/6-311G（d, p） level was applied to exploring the inhibition mechanism of cholinesterases by carbamate. The results indicate that the inhibition reactions with or without the...The density functional theory at the B3LYP/6-311G（d, p） level was applied to exploring the inhibition mechanism of cholinesterases by carbamate. The results indicate that the inhibition reactions with or without the catalytic effect of the catalytic triad in eholinesterases underwent a two-step addition-elimination mechanism, which is in good agreement with the proposed mechanism. The solvent has a strong effect on the inhibition reactions and the reaction with the catalytic triad in the solvent phase is close to the real reaction under biological condition.展开更多
Objective:To investigate the effect of Cannabis sativa resin and/or tramadol,two commonly drugs of abuse on acetylcholinesterase and butyrylcholinesterase activities as a possible cholinergic biomarkers of neurotoxici...Objective:To investigate the effect of Cannabis sativa resin and/or tramadol,two commonly drugs of abuse on acetylcholinesterase and butyrylcholinesterase activities as a possible cholinergic biomarkers of neurotoxicity induced by these agents.Methods:rats were treated with cannabis resin(5,10 or 20 mg/kg)(equivalent to the active constituent A'-tetrahydrocannabinol),tramadol(5,10 and 20 mg/kg) or tramadol(10 mg/kg)combined with cannabis resin(5,10 and 20 mg/kg) subcutaneously daily for 6 weeks.Acetylcholinesterase(AChE) and butyrylcholinesterase(BChE) activities were measured in brain and serum.We also measured the activity of paraoxonase-1(PONl) in serum of rats treated with these agents.Results:(i) AChE activity in brain increased after 10-20 mg/kg cannabis resin(by 16.3%-36.5%).AChE activity in brain did not change after treatment with 5-20 mg/kg tramadol.The administration of both cannabis resin(5,10 or 20 mg/kg) and tramadol(10 mg/kg) resulted in decreased brain AChE activity by 14.1%,12.9%and 13.6%,respectively;(ii) BChE activity in serum was markedly and dose-dependenlly inhibited by cannabis resin(by 60.9%-76.9%).BChE activity also decreased by 17.6%-36.5%by 10-20mg/kg tramadol and by 57.2%-63.9%by the cannabis resin/tramadol combined treatment;(iii)Cannabis resin at dose of 20 mg/kg increased serum PONl activity by 25.7%.In contrast,tramadol given at 5,10 and 20 mg/kg resulted in a dose-dependent decrease in serum PON1 activity by 19%,36.7%,and 46.1%,respectively.Meanwhile,treatment with cannabis resin plus tramadol resulted in 40.2%,35.8%,30.7%inhibition of PONl activity compared to the saline group.Conclusions:these data suggest that cannabis resin exerts different effects on AChE and BChE activities which could contribute to the memory problems and the decline in cognitive function in chronic users.展开更多
Introduction: Dementia is frequently associated with Parkinson’s disease, especially in later stages. Efficacy of cholinesterase inhibitors (ChI) in Alzheimer’s dementia is well established. However, treatment with ...Introduction: Dementia is frequently associated with Parkinson’s disease, especially in later stages. Efficacy of cholinesterase inhibitors (ChI) in Alzheimer’s dementia is well established. However, treatment with ChI in Parkinson’s disease dementia (PDD) remains controversial. The objective of this systematic review and meta-analysis was to assess the effects of ChI in PDD. Methods: A comprehensive literature search was performed in MEDLINE, EMBASE and Cochrane library up to March 2014 using the descriptors “Parkinson’s disease”, “dementia in Parkinson’s disease”, “cognition”, “acetylcholinesterase inhibitors”, “cholinesterase inhibitors”, “anticholinesterase agents”, “rivastigmine”, “donepezil” and “galantamine” (Pubmed search strategy). All randomized, doubleblinded, placebo-controlled trials that met the eligibility criteria and assessed the effects of ChI in PDD were considered for analysis. There were no restrictions regarding paper language. Summary effect-sizes were presented as standardized mean differences (SMD) and the pooled analysis was performed with a fixed-effects model. Outcomes considered for analysis were the Mini Mental Status Exam (MMSE) score and the cognition scale for evaluation of dementia ADAS-Cog. The degree of heterogeneity between included studies was assessed through the I2 test. Results: After a comprehensive search, 175 references were retrieved. From these, five randomized trials involving 946PDD subjects were included in the review. Four studies used donepezil and only one study used rivastigmine. The pooled analysis of five studies that assessed the effects of ChI in MMSE total score showed a SMD of 0.24 (CI 95% 0.11 - 0.38). Three studies considered the effects of ChI on Adas-Cog and the pooled results showed a SMD of 0.21 (CI 95% 0.07 - 0.35). There was no significant heterogeneity between the studies. Conclusions: The results of this systematic review and meta- analysis suggest that ChI improves cognitive impairment in PDD subjects. Despite statistically significant, the translation of these results into relevant clinical improvement should be taken with caution, as the studies did not address what would be considered a clinically significant result.展开更多
Cholinergic dysfunction is common to Alzheimer’s dementia and Schizophrenia. The objective of this study is to undertake a systematic review and meta-analysis of the literature on the cognitive and clinical effects o...Cholinergic dysfunction is common to Alzheimer’s dementia and Schizophrenia. The objective of this study is to undertake a systematic review and meta-analysis of the literature on the cognitive and clinical effects of cholinesterase inhibitors administered to patients with schizophrenia and co-morbid Alzheimer’s disease dementia. A literature search of the MEDLINE, CINAHL, PubMed, PsycINFO, EMBASE, AMED, BNI, HMIC and Health Business Elite databases has been performed (up to January 2013) to investigate the use of cholinesterase inhibitors in patients with schizophrenia and dementia. The terms “schizophrenia”, “dementia”, “rivastigmine”, “donepezil”, “galantamine” and “cognitive deficit” have been searched, with a restriction for English language. Five published studies including 1 RCT have been included for the qualitative review. Treatments include Donepezil 5 mg and 10 mg as well as Rivastigmine 9 mg. The numbers of participants vary from 2 incase report to20 inthe RCT. Only 1 study qualifies for meta-analysis. There is a very limited evidence on the efficacy and safety of using acetylcholinesterase inhibitors in the management of dementia co-morbid with schizophrenia. The only randomised controlled study shows lack of evidence in terms of efficacy in using cholinesterase inhibitors in the management of dementia with schizophrenia. Future research projects will have to look at an adequate sample size to explore treatment on various cognitive and noncognitive domains and the sample should be selected by using definitive and internationally acceptable diagnostic criteria.展开更多
Two novel naphthol derivatives（1 and 2） were synthesized and characterized via IR,~1H NMR,and HRMS.The structure of compound 2 was verified by single-crystal X-ray crystallography.It crystallizes in monoclinic,space...Two novel naphthol derivatives（1 and 2） were synthesized and characterized via IR,~1H NMR,and HRMS.The structure of compound 2 was verified by single-crystal X-ray crystallography.It crystallizes in monoclinic,space group C2/c with a = 21.6725（9）,b = 6.0127（3）,c = 25.5405（14） A,β = 94.716（5）o,V = 3316.9（3） A^3,Z = 8,F（000） = 1384,D_c = 1.511 Mg/m^3,M_r = 377.22 and μ = 2.487 mm^-1.In addition,their cholinesterase inhibitory activities in vitro toward Electrophorus electricus acetylcholinesterase（eel ACh E） and horse serum butyrylcholinesterase（eq BCh E） were further determined.The results showed that compound 1 as a new acetylcholinesterase（ACh E） inhibitor displayed higher ACh E inhibitory activity（IC_（50） = 1.4 μM）,which could be considered for Alzheimer＇s disease therapeutics.展开更多
<strong>Objective:</strong> To evaluate early prediction value of IPS<span> </span><span><span style="font-family:Verdana;">combined with SchE and D-dimer detection for in...<strong>Objective:</strong> To evaluate early prediction value of IPS<span> </span><span><span style="font-family:Verdana;">combined with SchE and D-dimer detection for infection and survival in critically ill patients. </span><b><span style="font-family:Verdana;">Methods:</span></b></span><b><span> </span></b><span style="font-family:Verdana;">199 critically ill patients admitted to the emergency intensive care unit (EICU) of our hospital from December 2018 to December 2019 were retrospectively analyzed, including 110 infection patients (infection group) and 89 non-infection</span><span> </span><span style="font-family:Verdana;">patients (non-infection group).</span><span> </span><span><span style="font-family:Verdana;">According to the survival, the infection group was divided into death group (68 cases) and survival group (42 cases). The IPS, APACHE II, SOFA and SchE, D-dimer expression levels were detected and compared;Univariate and logistic regression analysis were used to evaluate the independent prognostic factors. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">The IPS and APACHE II of patients in the infected group were higher than those in the non-infected group, the level of SchE was lower than that in the non-infected group, and the level of D-dimer was higher than that in the non-infected group (</span><i><span style="font-family:Verdana;">P</span></i></span><i><span> </span></i><span style="font-family:Verdana;"><</span><span> </span><span style="font-family:Verdana;">0.001). IPS, SOFA, APACHE</span><span style="font-family:Verdana;"> II</span><span style="font-family:Verdana;">, SchE, D-dimer, invasive mechanical ventilation, septic shock, and ICU length</span><span style="font-family:Verdana;"> of stay had significant influence on the prognosis of critically ill patients</span><span> </span><span><span style="font-family:Verdana;">(</span><i><span style="font-family:Verdana;">P</span></i></span><i><span> </span></i><span style="font-family:Verdana;"><</span><span> </span><span><span style="font-family:Verdana;">0.001). Logistic regression analysis showed that IPS (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 2.821, </span><span><span style="font-family:Verdana;">95%</span><i><span style="font-family:Verdana;"> CI</span></i></span><span style="font-family:Verdana;"> 1.501</span></span><span style="font-family:Verdana;"> - </span><span><span style="font-family:Verdana;">5.227), SOFA (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 5.078, </span><span><span style="font-family:Verdana;">95% </span><i><span style="font-family:Verdana;">CI</span></i></span><span style="font-family:Verdana;"> 3.327 </span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;"> 7.690), APACHE II (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 14.308, </span><span><span style="font-family:Verdana;">95% </span><i><span style="font-family:Verdana;">CI</span></i></span><span style="font-family:Verdana;"> 8.901 </span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;"> 21.893), SchE (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 0.223, </span><span><span style="font-family:Verdana;">95%</span><i><span style="font-family:Verdana;"> CI</span></i></span><span style="font-family:Verdana;"> 0.165 </span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> 0.291), D-dimer</span><span style="font-family:Verdana;"> (</span><i><span style="font-family:Verdana;">OR</span></i><i><span> </span></i><span style="font-family:Verdana;">=</span><span> </span><span style="font-family:Verdana;">2.10</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">95%</span><i><span> </span></i><i><span style="font-family:Verdana;">CI</span></i><i><span> </span></i><span style="font-family:Verdana;">1.55</span><span style="font-family:Verdana;"> - </span><span style="font-family:Verdana;">2.85</span><span style="font-family:Verdana;">)</span><span><span style="font-family:Verdana;">, septic shock (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 9.948,</span></span><span> </span><span style="font-family:Verdana;">95%</span><span> </span><i><span style="font-family:Verdana;">CI</span></i><span style="font-family:Verdana;"> 7.012</span><span style="font-family:Verdana;"> - </span><span style="font-family:Verdana;">17.012)</span><span> </span><span style="font-family:Verdana;">were independent factors affecting the prognosis of critically ill patients with infection</span><span style="font-family:Verdana;"> (</span><i><span style="font-family:Verdana;">P</span></i><span> </span><span style="font-family:Verdana;"><</span><span> </span><span style="font-family:Verdana;">0.001</span><span style="font-family:Verdana;">)</span><span style="font-family:Verdana;">.</span><span> </span><b><span style="font-family:Verdana;">Conclusion:</span></b><b><span> </span></b><span style="font-family:Verdana;">IPS and D-dimer expression level in infected patients were increased and SchE decreased significantly compared with those in non-infected patients, and they significantly correlated with</span><span> </span><span style="font-family:Verdana;">disease severity of infected</span><span> </span><span style="font-family:Verdana;">patients</span><span> </span><span style="font-family:Verdana;">and could be early prediction</span><span> </span><span style="font-family:Verdana;">for prognosis.</span>展开更多
Objective: To study the changes of serum pancreatic stone protein (PSP) and cholinesterase (ChE) contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage. Meth...Objective: To study the changes of serum pancreatic stone protein (PSP) and cholinesterase (ChE) contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage. Methods: A total of 64 children with sepsis who were treated in the hospital between January 2015 and January 2017 were selected as observation group, and 50 healthy children who received vaccination in the hospital during the same period were selected as normal control group. The contents of PSP, ChE, inflammatory factors as well as liver and kidney function indexes in the two groups were detected. Pearson test was used to assess the correlation of serum PSP and ChE contents with systemic inflammatory response and target organ damage in children with sepsis. Results: Serum PSP content of observation group was higher than that of control group while ChE content was lower than that of control group;serum inflammatory factors PCT, CRP, IL-1, IL-6 and IL-10 contents of observation group were higher than those of normal control group;liver function indexes TBIL, ALT and AST contents were higher than those of normal control group;kidney function indexes Scr and BUN contents were higher than those of normal control group. Pearson test showed that the serum PSP and ChE contents in children with sepsis were directly correlated with the systemic inflammatory response as well as liver and renal function injury. Conclusion: Serum PSP content significantly increases while ChE content significantly decreases in children with sepsis and the specific change is directly correlated with the overall disease severity.展开更多
Objective:To investigate effects of hemoperfusion and hemofiltration combination on treating patients with acute organophosphours pesticide poisoning (AOPP) and influence of it on cholinesterase, dopamine and inflamma...Objective:To investigate effects of hemoperfusion and hemofiltration combination on treating patients with acute organophosphours pesticide poisoning (AOPP) and influence of it on cholinesterase, dopamine and inflammatory factors.Methods:A total of 82 cases of AOPP patients treated in our hospital from Sep 2012 to Jul 2016 were selected as subjects. They were randomly divided to be the observation group and the control group, 41 cases for each. For patients in observation group, combined therapy of hemoperfusion (HP) and hemofiltration (HF) were provided. For patients in control group, combined therapy of HP and hemodialysis (HD) were provided. Effects on the two groups of patients were compared. Meanwhile, cholinesterase, dopamine and inflammatory factors levels in different times before and after treatment were compared.Results:Consciousness improvement times and hospitalization times in observation group were significantly lower than in control group. No significant difference showed on fatality rates between the two groups. Before treatment, no significant difference showed on CHE and DE levels between two groups of patients;6 h and 12 h after treatment, CHE average levels in two groups were significantly higher than before treatment in the same group, and levels in observation group at the same phase were significantly higher than in control group;6 h and 12 h after treatment, DA levels in observation group were significantly lower than the same group before treatment, and significantly lower than control group, while 12 h after treatment, DA levels in control group were significantly lower than the same group before treatment. Before treatment, no significant difference showed on serum TGF-β1, TNF-α, IL-6, IL-8 between two groups of patients. After treatment, each index levels in two groups were significantly lower than the same group before treatment, and levels in observation group at the same phase were significantly lower than control group. Conclusion:Effects of blood purification therapy on treating AOPP were worth approving, but effects of HP and HF combined therapy were more significant. In addition, improvement of HP+HF on CHE, DA and inflammatory factors were better than HP+HD.展开更多
A novel Acetazolamide condensed 1,4-dihydropyridines was set up by treating of N-(5-acetamido-1,3,4-thiadiazol-2-ylsulfonyl)-3-oxobutanamide with an aryl aldehyde and 25-30%alkali with sight amount of barium nitrate a...A novel Acetazolamide condensed 1,4-dihydropyridines was set up by treating of N-(5-acetamido-1,3,4-thiadiazol-2-ylsulfonyl)-3-oxobutanamide with an aryl aldehyde and 25-30%alkali with sight amount of barium nitrate as a catalyst.Confirmation of the synthetic structure of the titled compounds(4-16)was substantiated by thin-layer chromatography(TLC),IR,^(1)H NMR,^(13)C NMR,Mass spectra(MS)and elemental analysis(C,H,and N)were finished.The titled compounds were assessed for anticholinesterase activity against acetylcholinesterase and butyl cholinesterase enzymes.The titled compound produced weak,moderate,or high anticholinesterase activity.Particularly,compound 8 demonstrated the best anticholinesterase activity of all the 1,4-dihydropyridines,with an IC_(50) estimation of 0.08μM and 2.9μM.展开更多
Dementia is a group of diseases,including Alzheimer's disease(AD),vascular dementia,Lewy body dementia,frontotemporal dementia,Parkinson's disease dementia,metabolic dementia and toxic dementia.The treatment o...Dementia is a group of diseases,including Alzheimer's disease(AD),vascular dementia,Lewy body dementia,frontotemporal dementia,Parkinson's disease dementia,metabolic dementia and toxic dementia.The treatment of dementia mainly includes symptomatic treatment by controlling the primary disease and accompanying symptoms,nutritional support therapy for repairing nerve cells,psychological auxiliary treatment,and treatment that improves cognitive function through drugs.Among them,drug therapy to improve cognitive function is important.This review focuses on introducing and commenting on some recent progress in exploring drugs to improve cognitive function,especially the new progress in drug treatment for AD.We mainly discuss the opportunities and challenges in finding and developing new therapeutic drugs from the aspects of acetylcholinesterase,N-methyl-D-aspartate glutamate receptor,amyloid protein,tau protein and chronic immune inflammation.展开更多
Due to their significant value in both economy and ecology,Daphnia had long been employed to investigate in vivo response of cholinesterase(ChE) in anticholinesterase exposures,whereas the type constitution and proper...Due to their significant value in both economy and ecology,Daphnia had long been employed to investigate in vivo response of cholinesterase(ChE) in anticholinesterase exposures,whereas the type constitution and property of the enzyme remained unclear.A type of ChE was purified from Daphnia magna using a three-step procedure,i.e.,Triton X-100 extraction,ammonium sulfate precipitation,and diethylaminoethyl(DEAE)-Sepharose Fast-Flow chromatography.According to sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE),molecular mass of the purified ChE was estimated to be 84 kDa.Based on substrate studies,the purified enzyme preferred butyrylthiocholine iodide(BTCh) [with maximum velocity(Vmax)/Michaelis constant(Km)=8.428 L/(min·mg protein)] to acetylthiocholine iodide(ATCh) [with V max /Km =5.346 L/(min·mg protein)] as its substrate.Activity of the purified enzyme was suppressed by high concentrations of either ATCh or BTCh.Inhibitor studies showed that the purified enzyme was more sensitive towards inhibition by tetraisopropylpyrophosphoramide(iso-OMPA) than by 1,5-bis(4-allyldimethylammoniumphenyl) pentan-3-one dibromide(BW284C51).Result of the study suggested that the purified ChE was more like a type of pseudocholinesterase,and it also suggested that Daphnia magna contained multiple types of ChE in their bodies.展开更多
Background Some studies found that cholinesterase （ChE） can be an independent risk factor for patients with multiple organ dysfunction syndrome. To assess aged patients with systemic inflammatory response syndrome ...Background Some studies found that cholinesterase （ChE） can be an independent risk factor for patients with multiple organ dysfunction syndrome. To assess aged patients with systemic inflammatory response syndrome （SIRS） early and predict their prognosis, the predictive value of ChE for the prognosis of aged patients with SIRS was analyzed. Methods From September 2009 to September 2010, all aged patients with SIRS in the ICU of the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed if they met inclusion criteria： patients aged 〉65 years and met American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria for SIRS. Serum ChE, albumin, D-dimer, lactic acid and C-reactive protein （CRP） were measured, and the Acute Physiology and Chronic Health Evaluation （APACHE） II and Glasgow Coma Scale （GCS） scores were evaluated within the first 24 hours in the ICU. Fisher＇s exact test was used for comparison of the primary disease between the deceased group and surviving group. For comparison of study variables between the two groups, the Student＇s t test or Mann-Whitney U test was used. Multivariate significance was tested with binary Logistic regression analysis. Results The clinical data of 124 aged patients with SIRS were collected and analyzed. Sixty-six patients （46 male, 20 female, mean age （78.70±8.08） years） who died were included in the deceased group and 58 patients （34 male, 24 female, mean age （76.02±6.57） years） who survived were included in the surviving group. There were no significant differences in age, gender, APACHE II score and GCS score between the deceased group and surviving group （all P 〉0.05）, but there were significant differences in lactic acid （P=0.011）, D-dimer （P=0.011）, albumin （P=0.007）, CRP （P=0.008）, and ChE （P 〈0.0001）. The correlation analysis showed that the APACHE II score and CRP were not correlated with ChE （both P 〈0.05）. D-dimer and albumin were correlated with ChE （Spearman＇s rho correlation coefficients were -0.206 and 0.324, the corresponding P values were 0.022 and 〈0.0001）. Multiple Logistic regression analysis showed that age, gender, lactic acid, D-dimer, albumin, CRP, APACHE II score, and GCS score were not independent risk factors for prognosis of aged patients with SIRS, but that ChE was （P 〈0.0001）. The receiver operating characteristic curve of ChE had an area under the curve of 0.797 （standard error=0.04; P 〈0.0001）, and a ChE of 103.00 U/L was the cut-off value with sensitivity=0.793, specificity=0.742. Conclusion Serum ChE might be a predictive marker for the prognosis of aged patients with SIRS, with low serum ChE levels indicating poor prognosis.展开更多
Background The nervous system, through the vagus nerve and its neurotransmitter acetylcholine, can down-regulate the systemic inflammation in vivo, and recently, a role of brain cholinergic mechanisms in activating th...Background The nervous system, through the vagus nerve and its neurotransmitter acetylcholine, can down-regulate the systemic inflammation in vivo, and recently, a role of brain cholinergic mechanisms in activating this cholinergic anti-inflammatory pathway has been indicated. Galanthamine is a cholinesterase inhibitor and one of the centrally acting cholinergic agents available in clinic. This study aimed to evaluate the effect of galanthamine on circulating tumor necrosis factor alpha （TNF-a） in rats with lipopolysaccharide-induced peritonitis and the possible role of the vagus nerve in the action of galanthamine. Methods Rat models of lipopolysaccharide-induced peritonitis and bilateral cervical vagotomy were produced. In the experiment 1, the rats were randomly divided into control group, peritonitis group, and peritonitis groups treated with three dosages of galanthamine. In the experiment 2, the rats were randomly divided into sham group, sham plus peritonitis group, sham plus peritonitis group treated with galanthamine, vagotomy plus peritonitis group, and vagotomy plus peritonitis group treated with galanthamine. The levels of plasma TNF-α were determined in every group. Results The level of circulating TNF-α was significantly increased in rats after intraperitoneal injection of endotoxin. Galanthamine treatment decreased the level of circulating TNF-α in rats with lipopolysaccharide-induced peritonitis, and there was significant difference compared with rats with lipopolysaccharide-induced peritonitis without treatment. The 3 mg/kg dosage of galanthamine had the most significant inhibition on circulating TNF-α level at all the three tested doses. Galanthamine obviously decreased the TNF-a level in rats with lipopolysaccharide-induced peritonitis with sham operation, but could not decrease the TNF-α level in rats with lipopolysaccharide-induced peritonitis with vagotomy. Conclusion Cholinesterase inhibitor galanthamine has an inhibitory effect on TNF-α release in rats with Iipopolysaccharide-induced peritonitis, and the vagus nerve plays a role in the process of the action of galanthamine.展开更多
Background:Hand,foot,and mouth disease(HFMD)caused by enterovirus 71(EV71)is a potentially life-threatening infectious disease that commonly occurs in children.Diagnosis of HFMD caused by EV71 largely depends on clini...Background:Hand,foot,and mouth disease(HFMD)caused by enterovirus 71(EV71)is a potentially life-threatening infectious disease that commonly occurs in children.Diagnosis of HFMD caused by EV71 largely depends on clinical manifestations and rare serological biomarkers used to identify children suffering from HFMD.Serum cholinesterase(SChE)activity has frequently been reported as a potential biomarker for solid central nervous system tumors,chronic heart failure,and liver cirrhosis.However,its potential value in the diagnosis of neurotropic virus infections,such as HFMD caused by EV71,remains to be determined.Findings:In our study,220 children hospitalized with HFMD caused by EV71,34 inpatients infected with coxsackievirus A16(CVA16),and 43 undefined enterovirus-infected HFMD inpatients were recruited at the Anhui Provincial Children’s Hospital between January 2011 and December 2012.SChE activity was measured.The non-parametric Mann–Whitney U test showed that SChE activity in children diagnosed with HFMD caused by EV71 was significantly higher than in healthy controls(p<0.001),as well as in children with upper respiratory tract infections(p=0.011),bronchopneumonia(p<0.001),septicemia(p<0.001),amygdalitis(p<0.001),and appendicitis(p<0.001).In addition,higher SChE activity was observed in male inpatients with HFMD caused by EV71(47.7%positivity)compared to female inpatients(26.1%positivity)(chi-square test,p=0.002).In our study,no significant differences in SChE levels were observed among different ages(up to 120 months)(r=-0.112,p>0.05).An important finding was that SChE activity declined in the recovery phase of HFMD caused by EV71 compared to the acute phase(p<0.001).Conclusions:Elevated SChE activity was observed in patients with severe HFMD caused by EV71.Therefore,SChE might be a potential assistant biomarker for the diagnosis of HFMD caused by EV71 in children.展开更多
文摘Acetylcholine is an essential neurotransmitter found throughout the nervous system. Its action on postsynaptic receptors is regulated through hydrolysis by various carboxylesterases, especially cholinesterases (ChEs). The acute toxicity of organophosphate (OP) compounds is directly linked to their action as inhibitors of ChE. One widely used assay for evaluating ChE activity is a spectrophotometric method developed by Ellman et al. When the enzyme source is from tissues or, in particular, blood, hemoglobin displays a spectrophotometric peak at the same wave-length used to analyze cholinergic activity. This creates a substantial background that interferes with the Ellman’s assay and must be overcome in order to accurately monitor cholinesterase activity. Herein, we directly compare blood processing methods: classical method (1.67 ± 0.30 U/mL) and HemogloBindTM treatment (1.51 ± 0.17 U/mL), and clearly demonstrate that pretreatment of blood samples with HemoglobindTM is both a sufficient and rapid sample preparation method for the assessment of ChE activity using the Ellman’s method.
文摘To determine the predictive performance of cholinesterase compared to existing prognostic models in evaluating liver function in patients with chronic hepatitis D. METHODSIn an observational, cross-sectional and retrospective study, consecutive patients with hepatitis D cirrhosis were evaluated. Demographic, clinical and laboratory parameters were recorded. Serum cholinesterase levels were correlated with existing scoring models for chronic liver disease and Liver function tests. Receiver operating characteristic (ROC) curves were constructed to find an optimal cholinesterase level predicting ascites, Child Turcotte Pugh (CTP) score ≥ 10, model for end stage liver disease (MELD) score ≥ 15, baseline-event-anticipation (BEA) score for hepatitis D ≥ 5 and the aspartate transaminase to Platelet Ratio Index (APRI) ≥ 1.5. RESULTSThis study investigated 233 patients with chronic liver disease due to hepatitis D; 192 were male, median age 42 (16-69 years). Fifty patients had ascites and 15 had encephalopathy. One hundred and sixty-seven (71.7%) were in Child class A, 52 (22.3%) in Child class B and 14 (5.0%) in class C. A MELD score of 15 or more was seen in 24 patients. Cholinesterase levels correlated well with the INR, albumin, CTP score, MELD, MELD sodium, BEA and APRI scores (P < 0.001 each). Area under the ROC curve for ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5, APRI ≥ 1.5 was 0.836, 0.966, 0.913, 0.871 and 0.825 respectively (P < 0.001 each). Cut off values of cholinesterase (IU/L) for predicting ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5 and APRI ≥ 1.5 were < 3812, < 2853, < 2829, < 4719 and < 3954 with a sensitivity of 80%, 100%, 91.67%, 82.50%, 58.0% and specificity of 81.97%, 84.79%, 87.56%, 77.06% and 55.64% respectively. CONCLUSIONSerum cholinesterase demonstrates promising correlations with serum albumin, INR and CTP, MELD, BEA and APRI scores and is predictive of liver reserves in hepatitis D cirrhosis.
文摘The results confirmed that diazepam inhibits the cholinesterase in rat serum,red cell,corpus striatum and diaphragm in vitro,that the higher the diazepam concentration,the stronger the cholinesterase inhibition,and that diazepam is a reversible inhibitor to acetylcholinesterase and diazepam has a stabilizing action on red cell membranes.The role of these effects of diazepam in the treatment of organic phosphate poisoning is discussed
文摘AIM: To understand the correlation of serum cholinesterase (CHE) activity with gastric cancer and to assess their clinical significance.METHODS: The velocity method was adopted to detect the activity of serum CHE in patients with gastric cancer and in patients with non-malignant tumor as controls.RESULTS: The serum CHE activity in the treatment group was significantly lower than that in the control group with a very significant difference between the two groups (83.3:113.1,P = 0.0003). Age was significantly associated with the incidence of gastric caner.CONCLUSION: Serum CHE activity has a close relation with the incidence of gastric cancer.
文摘AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM HCI.Nizatidine,neostigmine,carbachol or famotidine was administered i.v.as a single injection. RESULTS Intravenous administration of nizatidine(3-30 mg/kg)dose-dependently increased duodenal HCO_3^- secretion,and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg.This nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility,mimicked by i.v.injection of neostigmine(0.03 mg/kg),and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin,a cyclooxygenase inhibitor,or N^G-nitro-L-arginine methyl ester,a NO synthase inhibitor.The HCO_3^- secretory response to acetylcholine(0.001 mg/kg)was significantly potentiated by the concurrent administration of nizatidine(3mg/kg,i.v.).The IC_(50)of nizatidine for AChE of rat erythrocytes was 1.4×10^(-6)M,about 12 times higher than that of neostigmine.Neither famotidine(>10^(-3)M, 30mg/kg,i.v.)nor cisapride(> 10^(-3)M, 3mg/kg,i.v.)had any influence on AChE activity or duodenal HCO_3^- secretion.Duodenal damage induced by acid perfusion(100 mM HCI for 4 h)in the presence of indomethacin was significantly prevented by nizatidine and neostigmine,at the doses that increased the HCO_3^- secretion. CONCLUSION Nizatidine stimulates duodenal HCO_3^- secretion,in both vagal-dependent and atropine-sensitive manners,and the action is associated with the anti-AChE activity of this agent.
基金the Scientific and Technological Research Council of Turkey(TUBITAK)for the scholarship provided her for Ph.D.program
文摘Objective:To explore cholinesterase inhibitory and antioxidant effect of six coniferous trees(Abies bornmulleriana,Picea pungens,Juniperus communis,Cedrus libani,Taxus baccata,and Cupressus sempervirens var.horizantalis).Methods:Acetone(Ace),ethyl acetate(EtOAc),and ethanol(EtOH)extracts prepared from the needles and shoots of the six coniferous trees were screened for their acetylcholinesterase(AChE)and butyrylcholinesterasc(BChE)inhibitory activity at 100μg/mL.Antioxidant activity of the extracts was tested using 2,2-diphenyl-1-picrylhydrazyl(DPPH)and N,N-dimethyl-p-phenylendiamine(DMPD)radical scavenging,nietal-chelation capacity,ferric-(FRAP)and phosphomolibdenum-reducing antioxidant power(PRAP)assays.All of the assays were performed in ELISA microplate reader.Total phenol and flavonoid amounts in the extracts were determined spectrophotometrically.Results:Among thirty-six extracts in total,the shoot-Ace extract of Cupressus sempervirens var.horizantalis exerted the highest inhibition against AChE[(54.84±2.51)%],while the needle-Ace extract of Cedrus libani was the most effective in inhibiting BChE[(67.54±0.30)%].The highest DPPH radical scavenging effect,FRAP and PRAP was observed in the shoot-Ace and EtOAc extracts from Taxus baccata.whereas all the extracts showed a variable degree of scavenging effect against DPMD radical.The shoot-EtOAc extract of Cedrus libani had the highest metalchelation capacity[(58.04±0.70)%].The shoot extracts of Taxus baccata were determined to have the richest total phenol content,which may contribute to its marked antioxidant activity.Conclusions:The conifer species screened in this study may contain cholinesterase-inhibiting and antioxidant properties,which might be useful against Alzheimer's disease.
基金Supported by the National Natural Science Foundation of China(Nos.20333050 and 20673044), PCSIRT(No.IRT0625) Key Subject of Science and Technology by Jilin Province, China
文摘The density functional theory at the B3LYP/6-311G（d, p） level was applied to exploring the inhibition mechanism of cholinesterases by carbamate. The results indicate that the inhibition reactions with or without the catalytic effect of the catalytic triad in eholinesterases underwent a two-step addition-elimination mechanism, which is in good agreement with the proposed mechanism. The solvent has a strong effect on the inhibition reactions and the reaction with the catalytic triad in the solvent phase is close to the real reaction under biological condition.
文摘Objective:To investigate the effect of Cannabis sativa resin and/or tramadol,two commonly drugs of abuse on acetylcholinesterase and butyrylcholinesterase activities as a possible cholinergic biomarkers of neurotoxicity induced by these agents.Methods:rats were treated with cannabis resin(5,10 or 20 mg/kg)(equivalent to the active constituent A'-tetrahydrocannabinol),tramadol(5,10 and 20 mg/kg) or tramadol(10 mg/kg)combined with cannabis resin(5,10 and 20 mg/kg) subcutaneously daily for 6 weeks.Acetylcholinesterase(AChE) and butyrylcholinesterase(BChE) activities were measured in brain and serum.We also measured the activity of paraoxonase-1(PONl) in serum of rats treated with these agents.Results:(i) AChE activity in brain increased after 10-20 mg/kg cannabis resin(by 16.3%-36.5%).AChE activity in brain did not change after treatment with 5-20 mg/kg tramadol.The administration of both cannabis resin(5,10 or 20 mg/kg) and tramadol(10 mg/kg) resulted in decreased brain AChE activity by 14.1%,12.9%and 13.6%,respectively;(ii) BChE activity in serum was markedly and dose-dependenlly inhibited by cannabis resin(by 60.9%-76.9%).BChE activity also decreased by 17.6%-36.5%by 10-20mg/kg tramadol and by 57.2%-63.9%by the cannabis resin/tramadol combined treatment;(iii)Cannabis resin at dose of 20 mg/kg increased serum PONl activity by 25.7%.In contrast,tramadol given at 5,10 and 20 mg/kg resulted in a dose-dependent decrease in serum PON1 activity by 19%,36.7%,and 46.1%,respectively.Meanwhile,treatment with cannabis resin plus tramadol resulted in 40.2%,35.8%,30.7%inhibition of PONl activity compared to the saline group.Conclusions:these data suggest that cannabis resin exerts different effects on AChE and BChE activities which could contribute to the memory problems and the decline in cognitive function in chronic users.
文摘Introduction: Dementia is frequently associated with Parkinson’s disease, especially in later stages. Efficacy of cholinesterase inhibitors (ChI) in Alzheimer’s dementia is well established. However, treatment with ChI in Parkinson’s disease dementia (PDD) remains controversial. The objective of this systematic review and meta-analysis was to assess the effects of ChI in PDD. Methods: A comprehensive literature search was performed in MEDLINE, EMBASE and Cochrane library up to March 2014 using the descriptors “Parkinson’s disease”, “dementia in Parkinson’s disease”, “cognition”, “acetylcholinesterase inhibitors”, “cholinesterase inhibitors”, “anticholinesterase agents”, “rivastigmine”, “donepezil” and “galantamine” (Pubmed search strategy). All randomized, doubleblinded, placebo-controlled trials that met the eligibility criteria and assessed the effects of ChI in PDD were considered for analysis. There were no restrictions regarding paper language. Summary effect-sizes were presented as standardized mean differences (SMD) and the pooled analysis was performed with a fixed-effects model. Outcomes considered for analysis were the Mini Mental Status Exam (MMSE) score and the cognition scale for evaluation of dementia ADAS-Cog. The degree of heterogeneity between included studies was assessed through the I2 test. Results: After a comprehensive search, 175 references were retrieved. From these, five randomized trials involving 946PDD subjects were included in the review. Four studies used donepezil and only one study used rivastigmine. The pooled analysis of five studies that assessed the effects of ChI in MMSE total score showed a SMD of 0.24 (CI 95% 0.11 - 0.38). Three studies considered the effects of ChI on Adas-Cog and the pooled results showed a SMD of 0.21 (CI 95% 0.07 - 0.35). There was no significant heterogeneity between the studies. Conclusions: The results of this systematic review and meta- analysis suggest that ChI improves cognitive impairment in PDD subjects. Despite statistically significant, the translation of these results into relevant clinical improvement should be taken with caution, as the studies did not address what would be considered a clinically significant result.
文摘Cholinergic dysfunction is common to Alzheimer’s dementia and Schizophrenia. The objective of this study is to undertake a systematic review and meta-analysis of the literature on the cognitive and clinical effects of cholinesterase inhibitors administered to patients with schizophrenia and co-morbid Alzheimer’s disease dementia. A literature search of the MEDLINE, CINAHL, PubMed, PsycINFO, EMBASE, AMED, BNI, HMIC and Health Business Elite databases has been performed (up to January 2013) to investigate the use of cholinesterase inhibitors in patients with schizophrenia and dementia. The terms “schizophrenia”, “dementia”, “rivastigmine”, “donepezil”, “galantamine” and “cognitive deficit” have been searched, with a restriction for English language. Five published studies including 1 RCT have been included for the qualitative review. Treatments include Donepezil 5 mg and 10 mg as well as Rivastigmine 9 mg. The numbers of participants vary from 2 incase report to20 inthe RCT. Only 1 study qualifies for meta-analysis. There is a very limited evidence on the efficacy and safety of using acetylcholinesterase inhibitors in the management of dementia co-morbid with schizophrenia. The only randomised controlled study shows lack of evidence in terms of efficacy in using cholinesterase inhibitors in the management of dementia with schizophrenia. Future research projects will have to look at an adequate sample size to explore treatment on various cognitive and noncognitive domains and the sample should be selected by using definitive and internationally acceptable diagnostic criteria.
文摘Two novel naphthol derivatives（1 and 2） were synthesized and characterized via IR,~1H NMR,and HRMS.The structure of compound 2 was verified by single-crystal X-ray crystallography.It crystallizes in monoclinic,space group C2/c with a = 21.6725（9）,b = 6.0127（3）,c = 25.5405（14） A,β = 94.716（5）o,V = 3316.9（3） A^3,Z = 8,F（000） = 1384,D_c = 1.511 Mg/m^3,M_r = 377.22 and μ = 2.487 mm^-1.In addition,their cholinesterase inhibitory activities in vitro toward Electrophorus electricus acetylcholinesterase（eel ACh E） and horse serum butyrylcholinesterase（eq BCh E） were further determined.The results showed that compound 1 as a new acetylcholinesterase（ACh E） inhibitor displayed higher ACh E inhibitory activity（IC_（50） = 1.4 μM）,which could be considered for Alzheimer＇s disease therapeutics.
文摘<strong>Objective:</strong> To evaluate early prediction value of IPS<span> </span><span><span style="font-family:Verdana;">combined with SchE and D-dimer detection for infection and survival in critically ill patients. </span><b><span style="font-family:Verdana;">Methods:</span></b></span><b><span> </span></b><span style="font-family:Verdana;">199 critically ill patients admitted to the emergency intensive care unit (EICU) of our hospital from December 2018 to December 2019 were retrospectively analyzed, including 110 infection patients (infection group) and 89 non-infection</span><span> </span><span style="font-family:Verdana;">patients (non-infection group).</span><span> </span><span><span style="font-family:Verdana;">According to the survival, the infection group was divided into death group (68 cases) and survival group (42 cases). The IPS, APACHE II, SOFA and SchE, D-dimer expression levels were detected and compared;Univariate and logistic regression analysis were used to evaluate the independent prognostic factors. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">The IPS and APACHE II of patients in the infected group were higher than those in the non-infected group, the level of SchE was lower than that in the non-infected group, and the level of D-dimer was higher than that in the non-infected group (</span><i><span style="font-family:Verdana;">P</span></i></span><i><span> </span></i><span style="font-family:Verdana;"><</span><span> </span><span style="font-family:Verdana;">0.001). IPS, SOFA, APACHE</span><span style="font-family:Verdana;"> II</span><span style="font-family:Verdana;">, SchE, D-dimer, invasive mechanical ventilation, septic shock, and ICU length</span><span style="font-family:Verdana;"> of stay had significant influence on the prognosis of critically ill patients</span><span> </span><span><span style="font-family:Verdana;">(</span><i><span style="font-family:Verdana;">P</span></i></span><i><span> </span></i><span style="font-family:Verdana;"><</span><span> </span><span><span style="font-family:Verdana;">0.001). Logistic regression analysis showed that IPS (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 2.821, </span><span><span style="font-family:Verdana;">95%</span><i><span style="font-family:Verdana;"> CI</span></i></span><span style="font-family:Verdana;"> 1.501</span></span><span style="font-family:Verdana;"> - </span><span><span style="font-family:Verdana;">5.227), SOFA (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 5.078, </span><span><span style="font-family:Verdana;">95% </span><i><span style="font-family:Verdana;">CI</span></i></span><span style="font-family:Verdana;"> 3.327 </span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;"> 7.690), APACHE II (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 14.308, </span><span><span style="font-family:Verdana;">95% </span><i><span style="font-family:Verdana;">CI</span></i></span><span style="font-family:Verdana;"> 8.901 </span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;"> 21.893), SchE (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 0.223, </span><span><span style="font-family:Verdana;">95%</span><i><span style="font-family:Verdana;"> CI</span></i></span><span style="font-family:Verdana;"> 0.165 </span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> 0.291), D-dimer</span><span style="font-family:Verdana;"> (</span><i><span style="font-family:Verdana;">OR</span></i><i><span> </span></i><span style="font-family:Verdana;">=</span><span> </span><span style="font-family:Verdana;">2.10</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">95%</span><i><span> </span></i><i><span style="font-family:Verdana;">CI</span></i><i><span> </span></i><span style="font-family:Verdana;">1.55</span><span style="font-family:Verdana;"> - </span><span style="font-family:Verdana;">2.85</span><span style="font-family:Verdana;">)</span><span><span style="font-family:Verdana;">, septic shock (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 9.948,</span></span><span> </span><span style="font-family:Verdana;">95%</span><span> </span><i><span style="font-family:Verdana;">CI</span></i><span style="font-family:Verdana;"> 7.012</span><span style="font-family:Verdana;"> - </span><span style="font-family:Verdana;">17.012)</span><span> </span><span style="font-family:Verdana;">were independent factors affecting the prognosis of critically ill patients with infection</span><span style="font-family:Verdana;"> (</span><i><span style="font-family:Verdana;">P</span></i><span> </span><span style="font-family:Verdana;"><</span><span> </span><span style="font-family:Verdana;">0.001</span><span style="font-family:Verdana;">)</span><span style="font-family:Verdana;">.</span><span> </span><b><span style="font-family:Verdana;">Conclusion:</span></b><b><span> </span></b><span style="font-family:Verdana;">IPS and D-dimer expression level in infected patients were increased and SchE decreased significantly compared with those in non-infected patients, and they significantly correlated with</span><span> </span><span style="font-family:Verdana;">disease severity of infected</span><span> </span><span style="font-family:Verdana;">patients</span><span> </span><span style="font-family:Verdana;">and could be early prediction</span><span> </span><span style="font-family:Verdana;">for prognosis.</span>
文摘Objective: To study the changes of serum pancreatic stone protein (PSP) and cholinesterase (ChE) contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage. Methods: A total of 64 children with sepsis who were treated in the hospital between January 2015 and January 2017 were selected as observation group, and 50 healthy children who received vaccination in the hospital during the same period were selected as normal control group. The contents of PSP, ChE, inflammatory factors as well as liver and kidney function indexes in the two groups were detected. Pearson test was used to assess the correlation of serum PSP and ChE contents with systemic inflammatory response and target organ damage in children with sepsis. Results: Serum PSP content of observation group was higher than that of control group while ChE content was lower than that of control group;serum inflammatory factors PCT, CRP, IL-1, IL-6 and IL-10 contents of observation group were higher than those of normal control group;liver function indexes TBIL, ALT and AST contents were higher than those of normal control group;kidney function indexes Scr and BUN contents were higher than those of normal control group. Pearson test showed that the serum PSP and ChE contents in children with sepsis were directly correlated with the systemic inflammatory response as well as liver and renal function injury. Conclusion: Serum PSP content significantly increases while ChE content significantly decreases in children with sepsis and the specific change is directly correlated with the overall disease severity.
文摘Objective:To investigate effects of hemoperfusion and hemofiltration combination on treating patients with acute organophosphours pesticide poisoning (AOPP) and influence of it on cholinesterase, dopamine and inflammatory factors.Methods:A total of 82 cases of AOPP patients treated in our hospital from Sep 2012 to Jul 2016 were selected as subjects. They were randomly divided to be the observation group and the control group, 41 cases for each. For patients in observation group, combined therapy of hemoperfusion (HP) and hemofiltration (HF) were provided. For patients in control group, combined therapy of HP and hemodialysis (HD) were provided. Effects on the two groups of patients were compared. Meanwhile, cholinesterase, dopamine and inflammatory factors levels in different times before and after treatment were compared.Results:Consciousness improvement times and hospitalization times in observation group were significantly lower than in control group. No significant difference showed on fatality rates between the two groups. Before treatment, no significant difference showed on CHE and DE levels between two groups of patients;6 h and 12 h after treatment, CHE average levels in two groups were significantly higher than before treatment in the same group, and levels in observation group at the same phase were significantly higher than in control group;6 h and 12 h after treatment, DA levels in observation group were significantly lower than the same group before treatment, and significantly lower than control group, while 12 h after treatment, DA levels in control group were significantly lower than the same group before treatment. Before treatment, no significant difference showed on serum TGF-β1, TNF-α, IL-6, IL-8 between two groups of patients. After treatment, each index levels in two groups were significantly lower than the same group before treatment, and levels in observation group at the same phase were significantly lower than control group. Conclusion:Effects of blood purification therapy on treating AOPP were worth approving, but effects of HP and HF combined therapy were more significant. In addition, improvement of HP+HF on CHE, DA and inflammatory factors were better than HP+HD.
文摘A novel Acetazolamide condensed 1,4-dihydropyridines was set up by treating of N-(5-acetamido-1,3,4-thiadiazol-2-ylsulfonyl)-3-oxobutanamide with an aryl aldehyde and 25-30%alkali with sight amount of barium nitrate as a catalyst.Confirmation of the synthetic structure of the titled compounds(4-16)was substantiated by thin-layer chromatography(TLC),IR,^(1)H NMR,^(13)C NMR,Mass spectra(MS)and elemental analysis(C,H,and N)were finished.The titled compounds were assessed for anticholinesterase activity against acetylcholinesterase and butyl cholinesterase enzymes.The titled compound produced weak,moderate,or high anticholinesterase activity.Particularly,compound 8 demonstrated the best anticholinesterase activity of all the 1,4-dihydropyridines,with an IC_(50) estimation of 0.08μM and 2.9μM.
基金Supported by National Natural Science Foundation of China (General Program),No.32060182Qiannan Prefecture Science and Technology Plan Project in China,No.Qiannan Kehe She Zi[2022]No.1.
文摘Dementia is a group of diseases,including Alzheimer's disease(AD),vascular dementia,Lewy body dementia,frontotemporal dementia,Parkinson's disease dementia,metabolic dementia and toxic dementia.The treatment of dementia mainly includes symptomatic treatment by controlling the primary disease and accompanying symptoms,nutritional support therapy for repairing nerve cells,psychological auxiliary treatment,and treatment that improves cognitive function through drugs.Among them,drug therapy to improve cognitive function is important.This review focuses on introducing and commenting on some recent progress in exploring drugs to improve cognitive function,especially the new progress in drug treatment for AD.We mainly discuss the opportunities and challenges in finding and developing new therapeutic drugs from the aspects of acetylcholinesterase,N-methyl-D-aspartate glutamate receptor,amyloid protein,tau protein and chronic immune inflammation.
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY12B07008)the Department of Education of Zhejiang Province,China(No.20070138)
文摘Due to their significant value in both economy and ecology,Daphnia had long been employed to investigate in vivo response of cholinesterase(ChE) in anticholinesterase exposures,whereas the type constitution and property of the enzyme remained unclear.A type of ChE was purified from Daphnia magna using a three-step procedure,i.e.,Triton X-100 extraction,ammonium sulfate precipitation,and diethylaminoethyl(DEAE)-Sepharose Fast-Flow chromatography.According to sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE),molecular mass of the purified ChE was estimated to be 84 kDa.Based on substrate studies,the purified enzyme preferred butyrylthiocholine iodide(BTCh) [with maximum velocity(Vmax)/Michaelis constant(Km)=8.428 L/(min·mg protein)] to acetylthiocholine iodide(ATCh) [with V max /Km =5.346 L/(min·mg protein)] as its substrate.Activity of the purified enzyme was suppressed by high concentrations of either ATCh or BTCh.Inhibitor studies showed that the purified enzyme was more sensitive towards inhibition by tetraisopropylpyrophosphoramide(iso-OMPA) than by 1,5-bis(4-allyldimethylammoniumphenyl) pentan-3-one dibromide(BW284C51).Result of the study suggested that the purified ChE was more like a type of pseudocholinesterase,and it also suggested that Daphnia magna contained multiple types of ChE in their bodies.
文摘Background Some studies found that cholinesterase （ChE） can be an independent risk factor for patients with multiple organ dysfunction syndrome. To assess aged patients with systemic inflammatory response syndrome （SIRS） early and predict their prognosis, the predictive value of ChE for the prognosis of aged patients with SIRS was analyzed. Methods From September 2009 to September 2010, all aged patients with SIRS in the ICU of the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed if they met inclusion criteria： patients aged 〉65 years and met American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria for SIRS. Serum ChE, albumin, D-dimer, lactic acid and C-reactive protein （CRP） were measured, and the Acute Physiology and Chronic Health Evaluation （APACHE） II and Glasgow Coma Scale （GCS） scores were evaluated within the first 24 hours in the ICU. Fisher＇s exact test was used for comparison of the primary disease between the deceased group and surviving group. For comparison of study variables between the two groups, the Student＇s t test or Mann-Whitney U test was used. Multivariate significance was tested with binary Logistic regression analysis. Results The clinical data of 124 aged patients with SIRS were collected and analyzed. Sixty-six patients （46 male, 20 female, mean age （78.70±8.08） years） who died were included in the deceased group and 58 patients （34 male, 24 female, mean age （76.02±6.57） years） who survived were included in the surviving group. There were no significant differences in age, gender, APACHE II score and GCS score between the deceased group and surviving group （all P 〉0.05）, but there were significant differences in lactic acid （P=0.011）, D-dimer （P=0.011）, albumin （P=0.007）, CRP （P=0.008）, and ChE （P 〈0.0001）. The correlation analysis showed that the APACHE II score and CRP were not correlated with ChE （both P 〈0.05）. D-dimer and albumin were correlated with ChE （Spearman＇s rho correlation coefficients were -0.206 and 0.324, the corresponding P values were 0.022 and 〈0.0001）. Multiple Logistic regression analysis showed that age, gender, lactic acid, D-dimer, albumin, CRP, APACHE II score, and GCS score were not independent risk factors for prognosis of aged patients with SIRS, but that ChE was （P 〈0.0001）. The receiver operating characteristic curve of ChE had an area under the curve of 0.797 （standard error=0.04; P 〈0.0001）, and a ChE of 103.00 U/L was the cut-off value with sensitivity=0.793, specificity=0.742. Conclusion Serum ChE might be a predictive marker for the prognosis of aged patients with SIRS, with low serum ChE levels indicating poor prognosis.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 30500531）, and the Key Science and Technology Program of Zhejiang Province （No. 2007C33084）.
文摘Background The nervous system, through the vagus nerve and its neurotransmitter acetylcholine, can down-regulate the systemic inflammation in vivo, and recently, a role of brain cholinergic mechanisms in activating this cholinergic anti-inflammatory pathway has been indicated. Galanthamine is a cholinesterase inhibitor and one of the centrally acting cholinergic agents available in clinic. This study aimed to evaluate the effect of galanthamine on circulating tumor necrosis factor alpha （TNF-a） in rats with lipopolysaccharide-induced peritonitis and the possible role of the vagus nerve in the action of galanthamine. Methods Rat models of lipopolysaccharide-induced peritonitis and bilateral cervical vagotomy were produced. In the experiment 1, the rats were randomly divided into control group, peritonitis group, and peritonitis groups treated with three dosages of galanthamine. In the experiment 2, the rats were randomly divided into sham group, sham plus peritonitis group, sham plus peritonitis group treated with galanthamine, vagotomy plus peritonitis group, and vagotomy plus peritonitis group treated with galanthamine. The levels of plasma TNF-α were determined in every group. Results The level of circulating TNF-α was significantly increased in rats after intraperitoneal injection of endotoxin. Galanthamine treatment decreased the level of circulating TNF-α in rats with lipopolysaccharide-induced peritonitis, and there was significant difference compared with rats with lipopolysaccharide-induced peritonitis without treatment. The 3 mg/kg dosage of galanthamine had the most significant inhibition on circulating TNF-α level at all the three tested doses. Galanthamine obviously decreased the TNF-a level in rats with lipopolysaccharide-induced peritonitis with sham operation, but could not decrease the TNF-α level in rats with lipopolysaccharide-induced peritonitis with vagotomy. Conclusion Cholinesterase inhibitor galanthamine has an inhibitory effect on TNF-α release in rats with Iipopolysaccharide-induced peritonitis, and the vagus nerve plays a role in the process of the action of galanthamine.
基金supported by the National Natural Science Foundation of China(No:81271826).
文摘Background:Hand,foot,and mouth disease(HFMD)caused by enterovirus 71(EV71)is a potentially life-threatening infectious disease that commonly occurs in children.Diagnosis of HFMD caused by EV71 largely depends on clinical manifestations and rare serological biomarkers used to identify children suffering from HFMD.Serum cholinesterase(SChE)activity has frequently been reported as a potential biomarker for solid central nervous system tumors,chronic heart failure,and liver cirrhosis.However,its potential value in the diagnosis of neurotropic virus infections,such as HFMD caused by EV71,remains to be determined.Findings:In our study,220 children hospitalized with HFMD caused by EV71,34 inpatients infected with coxsackievirus A16(CVA16),and 43 undefined enterovirus-infected HFMD inpatients were recruited at the Anhui Provincial Children’s Hospital between January 2011 and December 2012.SChE activity was measured.The non-parametric Mann–Whitney U test showed that SChE activity in children diagnosed with HFMD caused by EV71 was significantly higher than in healthy controls(p<0.001),as well as in children with upper respiratory tract infections(p=0.011),bronchopneumonia(p<0.001),septicemia(p<0.001),amygdalitis(p<0.001),and appendicitis(p<0.001).In addition,higher SChE activity was observed in male inpatients with HFMD caused by EV71(47.7%positivity)compared to female inpatients(26.1%positivity)(chi-square test,p=0.002).In our study,no significant differences in SChE levels were observed among different ages(up to 120 months)(r=-0.112,p>0.05).An important finding was that SChE activity declined in the recovery phase of HFMD caused by EV71 compared to the acute phase(p<0.001).Conclusions:Elevated SChE activity was observed in patients with severe HFMD caused by EV71.Therefore,SChE might be a potential assistant biomarker for the diagnosis of HFMD caused by EV71 in children.
