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
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
AIM To examine whether nizatidine stimulatesduodenal HCO<sub>3</sub><sup>-</sup> secretion in rats by inhibitingAChE activity.METHODS Under pentobarbital anesthesia,aproximal duodenal loop was ...AIM To examine whether nizatidine stimulatesduodenal HCO<sub>3</sub><sup>-</sup> secretion in rats by inhibitingAChE activity.METHODS Under pentobarbital anesthesia,aproximal duodenal loop was perfused withsaline,and the HCO<sub>3</sub> secretion was measuredat pH 7.0 using a pH-stat method and by adding10mM HCI.Nizatidine,neostigmine,carbacholor famotidine was administered i.v.as a singleinjection.RESULTS Intravenous administration ofnizatidine（3-30 mg/kg）dose-dependentlyincreased duodenal HCO<sub>3</sub><sup>-</sup> secretion,and theeffect at 10mg/kg was equivalent to thatobtained by carbachol at 0.01 mg/kg.Thisnizatidine action was observed at the same doserange that inhibited acid secretion and enhancedgastric motility,mimicked by i.v.injection ofneostigmine（0.03 mg/kg）,and significantlyattenuated by bilateral vagotomy and prior s.c.administration of atropine but not byindomethacin,a cyclooxygenase inhibitor,orN<sup>G</sup>-nitro-L-arginine methyl ester,a NO synthaseinhibitor.The HCO<sub>3</sub><sup>-</sup> secretory response toacetylcholine（0.001 mg/kg）was significantlypotentiated by the concurrent administration ofnizatidine（3mg/kg,i.v.）.The IC<sub>50</sub>of nizatidine for AChE of rat erythrocytes was1.4×10<sup>-6</sup>M,about 12 times higher than that ofneostigmine.Neither famotidine(】10<sup>-3</sup>M,30mg/kg,i.v.)nor cisapride(】 10<sup>-3</sup>M,3mg/kg,i.v.)had any influence on AChEactivity or duodenal HCO<sub>3</sub><sup>-</sup> secretion.Duodenaldamage induced by acid perfusion（100 mM HCIfor 4 h）in the presence of indomethacin wassignificantly prevented by nizatidine andneostigmine,at the doses that increased theHCO<sub>3</sub><sup>-</sup> secretion.CONCLUSION Nizatidine stimulates duodenalHCO<sub>3</sub><sup>-</sup> secretion,in both vagal-dependent andatropine-sensitive manners,and the action isassociated with the anti-AChE activity of thisagent.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
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AIM To examine whether nizatidine stimulatesduodenal HCO<sub>3</sub><sup>-</sup> secretion in rats by inhibitingAChE activity.METHODS Under pentobarbital anesthesia,aproximal duodenal loop was perfused withsaline,and the HCO<sub>3</sub> secretion was measuredat pH 7.0 using a pH-stat method and by adding10mM HCI.Nizatidine,neostigmine,carbacholor famotidine was administered i.v.as a singleinjection.RESULTS Intravenous administration ofnizatidine（3-30 mg/kg）dose-dependentlyincreased duodenal HCO<sub>3</sub><sup>-</sup> secretion,and theeffect at 10mg/kg was equivalent to thatobtained by carbachol at 0.01 mg/kg.Thisnizatidine action was observed at the same doserange that inhibited acid secretion and enhancedgastric motility,mimicked by i.v.injection ofneostigmine（0.03 mg/kg）,and significantlyattenuated by bilateral vagotomy and prior s.c.administration of atropine but not byindomethacin,a cyclooxygenase inhibitor,orN<sup>G</sup>-nitro-L-arginine methyl ester,a NO synthaseinhibitor.The HCO<sub>3</sub><sup>-</sup> secretory response toacetylcholine（0.001 mg/kg）was significantlypotentiated by the concurrent administration ofnizatidine（3mg/kg,i.v.）.The IC<sub>50</sub>of nizatidine for AChE of rat erythrocytes was1.4×10<sup>-6</sup>M,about 12 times higher than that ofneostigmine.Neither famotidine(】10<sup>-3</sup>M,30mg/kg,i.v.)nor cisapride(】 10<sup>-3</sup>M,3mg/kg,i.v.)had any influence on AChEactivity or duodenal HCO<sub>3</sub><sup>-</sup> secretion.Duodenaldamage induced by acid perfusion（100 mM HCIfor 4 h）in the presence of indomethacin wassignificantly prevented by nizatidine andneostigmine,at the doses that increased theHCO<sub>3</sub><sup>-</sup> secretion.CONCLUSION Nizatidine stimulates duodenalHCO<sub>3</sub><sup>-</sup> secretion,in both vagal-dependent andatropine-sensitive manners,and the action isassociated with the anti-AChE activity of thisagent.
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.
