Effects of Cholinesterase Inhibitors in Cognition on Parkinson’s Disease Dementia: A Systematic Review and Meta-Analysis

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.

Cholinesterase inhibitors for co-morbid Alzhemer’s disease dementia and schizophrenia: Systematic review and meta-analysis

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.

Changes of serum pancreatic stone protein and cholinesterase contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage

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.

Searching for new drugs to treat Alzheimer’s disease dementia through multiple pathways

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.

Comparative efficacy and safety of cognitive enhancers for treating vascular cognitive impairment: systematic review and Bayesian network meta-analysis

Objective: To assess and compare the clinical efficacy and safety of cognitive enhancers(donepezil, galantamine, rivastigmine, and memantine) on cognition, behavior, function, and global status in patients with vascular cognitive impairment.Data sources: The initial literature search was performed with PubMed, EMBASE, the Cochrane Methodology Register, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing & Allied Health(CINAHL) from inception to January 2018 for studies regarding donepezil, galantamine, rivastigmine, and memantine for treatment of vascular cognitive impairment.Data selection: Randomized controlled trials on donepezil, galantamine, rivastigmine, and memantine as monotherapy in the treatment of vascular cognitive impairment were included. A Bayesian network meta-analysis was conducted. Outcome measures: Efficacy was assessed by changes in scores of the Alzheimer's Disease Assessment Scale, cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory scores and Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input, Activities of Daily Living, the Clinical Dementia Rating scale. Safety was evaluated by mortality, total adverse events(TAEs), serious adverse events(SAEs), nausea, vomiting. diarrhea, or cerebrovascular accidents(CVAs). Results: After screening 1717 citations, 12 randomized controlled trials were included. Donepezil and rivastigmine(mean difference(e) = –0.77, 95% confidence interval(CI): 0.25–1.32; MD = 1.05, 95% CI: 0.18–1.79) were significantly more effective than placebo in reducing Mini-Mental State Examination scores. Donepezil, galantamine, and memantine(MD = –1.30, 95% CI: –2.27 to –0.42; MD = –1.67, 95% CI: –3.36 to –0.06; MD = –2.27, 95% CI: –3.91 to –0.53) showed superior benefits on the Alzheimer's Disease Assessment Scale–cognitive scores compared with placebo. Memantine(MD = 2.71, 95% CI: 1.05–7.29) improved global status(Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input) more than the placebo. Safety results revealed that donepezil 10 mg(odds ratio(OR) = 3.04, 95% CI: 1.86–5.41) contributed to higer risk of adverse events than placebo. Galantamine(OR = 5.64, 95% CI: 1.31–26.71) increased the risk of nausea. Rivastigmine(OR = 16.80, 95% CI: 1.78–319.26) increased the risk of vomiting. No agents displayed a significant risk of serious adverse events, mortality, cerebrovascular accidents, or diarrhea.Conclusion: We found significant efficacy of donepezil, galantamine, and memantine on cognition. Memantine can provide significant efficacy in global status. They are all safe and well tolerated.

Serum cholinesterase: A predictive biomarker of hepatic reserves in chronic hepatitis D

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.

Effects of Diazepam on Rat Cholinesterase andMembrane Stability of Red Cell in vitro

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

Alterations of serum cholinesterase in patients with gastric cancer

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.

Stimulation by nizatidine,a histamine H_2-receptor antagonist,of duodenal HCO_3^-secretion in rats:relation to anti-cholinesterase activity

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.

In vitro cholinesterase inhibitory and antioxidant effect of selected coniferous tree species

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.

Inhibition Mechanism of Cholinesterases by Carbamate: A Theoretical Study

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.

Acetylcholinesterase,butyrylcholinesterase and paraoxonase 1 activities in rats treated with cannabis,tramadol or both

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.

Evaluation of HemogloBind^TMtreatment for preparation of samples for cholinesterase analysis

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.

Synthesis and Evaluation of Two Novel Naphthol Derivatives as Novel Cholinesterase Inhibitors

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.

The Prediction Value of the Infection Probability Score (IPS) Combined with Serum Cholinesterase and D-Dimer Detection for Infection and Survival in Critically Ill Patients

Objective: To evaluate early prediction value of IPS combined with SchE and D-dimer detection for infection and survival in critically ill patients. Methods: 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 patients (non-infection group). 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. Results: 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 (P < 0.001). IPS, SOFA, APACHE II, SchE, D-dimer, invasive mechanical ventilation, septic shock, and ICU length of stay had significant influence on the prognosis of critically ill patients (P < 0.001). Logistic regression analysis showed that IPS (OR = 2.821, 95% CI 1.501 - 5.227), SOFA (OR = 5.078, 95% CI 3.327 - 7.690), APACHE II (OR = 14.308, 95% CI 8.901 - 21.893), SchE (OR = 0.223, 95% CI 0.165 - 0.291), D-dimer (OR = 2.10, 95% CI 1.55 - 2.85), septic shock (OR = 9.948, 95% CI 7.012 - 17.012) were independent factors affecting the prognosis of critically ill patients with infection (P < 0.001). Conclusion: 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 disease severity of infected patients and could be early prediction for prognosis.

Effects of hemoperfusion and hemofiltration combination on treating patients with acute organophosphours pesticide poisoning and influence of it on cholinesterase, dopamine and inflammatory factors

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.

Predictive value of serum cholinesterase for the prognosis of 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.

Eleutheroside B or E enhances learning and memory in experimentally aged rats

Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer＇s disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E （50, 100, 200 mg/kg）, and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons.

Clinical correlates of hypotension in patients with acute organophosphorus poisoning

BACKGROUND:The aim of the present study is to describe the clinical correlates of hypotension and its associated outcomes in patients with acute organophosphorus poisoning(AOPP).METHODS:In this retrospective cohort study,we analyzed data pertaining to 871 patients with AOPP who were treated at two hospitals.Data from hypotensive and non-hypotensive patients were compared to identify clinical correlates of hypotension.We also evaluated the association between clinical parameters(including hypotension)and in-hospital mortality.RESULTS:The incidence of hypotension in AOPP patients was 16.4%.Hypotensive patients showed signifi cantly higher in-hospital mortality(1.1%vs.39.9%,P<0.001).Advanced age(odds ratio[OR]1.25,95%confi dence interval[CI]1.08–1.44),history of diabetes(OR 2.65,95%CI 1.14–5.96),and increased white blood cell count(OR 1.06,95%CI 1.03–1.09),plasma cholinesterase(OR 0.91,95%CI 0.84–0.94),plasma albumin(OR 0.88,95%CI 0.85–0.92),serum amylase(OR 1.01,95%CI 1.01–1.02),and blood pH(OR 0.64,95%CI 0.54–0.75)were signifi cantly associated with hypotension.After adjusting for potential confounders,hypotension was associated with increased in-hospital mortality(hazard ratio 8.77–37.06,depending on the controlled variables).CONCLUSIONS:Hypotension is a common complication of AOPP and is associated with increased in-hospital mortality.Advanced age,history of diabetes,and changes in laboratory parameters were associated with hypotension in AOPP patients.

Monitoring the level of serum paraoxonase 1 activity in liver transplantation patients

BACKGROUND: Paraoxonase 1(PON1) is an ester hydro- lase in serum and in the liver. Studies have suggested that PON1 measurement to the current battery of tests may im- prove the evaluation of chronic liver diseases. The aim of this study was to investigate the clinical significance of mo- nitoring the level of serum PON1 activity in liver transplan- tation patients. METHODS: A series of biochemical indexes were moni- tored in preoperative, operative and postoperative serum samples of 17 liver-transplanted patients. The change of se- rum PON1 level and its relations with other biochemical in- dexes were analyzed. RESULTS: PON1 was distributed normally in the healthy population and its reference value ranged from 45.5 to 265.8 U/mL. The PON1 level of all patients was lower than that of control group significantly (P<0.001); the level be- gan to elevate continuously 5 minutes after opening of the portal vein and was higher than that 90 minutes after open- ing of the portal vein ( P <0.05). Two days after operation it was still higher than the normal. The levels of serum ALT and AST elevated more significantly after opening of the portal vein than before operation and they were higher than the normal values till 2 days after the operation. CONCLUSIONS: The level of PON1 in serum may be taken as one of the effective indexes to assess whether the implant is alive and to monitor liver function of the patient together with other tests.