Behavioral and psychological symptoms including agitation are common in dementia,and are associated with decreased quality of life,increased risk of institutionalization,and greater patient and caregiver distress.Phar...Behavioral and psychological symptoms including agitation are common in dementia,and are associated with decreased quality of life,increased risk of institutionalization,and greater patient and caregiver distress.Pharmacological agents used for management of behavioral and psychological symptoms of dementia are limited by their tolerability,prompting a need for identifying efficacious and safe pharmacological treatments for managing agitation in dementia.The combination of dextromethorphan and quinidine sulfate is approved for pseudobulbar affect,and may be effective in managing agitation in dementia.A review of literature found only one randomized controlled trial that evaluated the use of dextromethorphan-quinidine for the management of agitation in dementia when compared to placebo.Data from this trial demonstrated that dextromethorphan-quinidine decreased agitation in dementia,and was well tolerated.Although promising,further research is needed before dextromethorphan-quinidine combination can be accepted as a standard treatment for agitation in dementia.展开更多
Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic bac...Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic background,the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes(iPSC-CMs)may help to reveal cell phenotype characteristics underlying different genetic variations.Here,to verify and compare the pathogenicity of mutations(SCN5A c.4213G>A and SCN1B c.590C>T)identified from two BrS patients,we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B,compared their structures and electrophysiology,and evaluated the safety of quinidine in patient-specific iPSC-derived CMs.Compared to the control group,BrS-CMs showed a significant reduction in sodium current,prolonged action potential duration,and varying degrees of decreased Vmax,but no structural difference.After applying different concentrations of quinidine,drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration(ETPC).The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.展开更多
Early afterdepolarization (EAD) in mouse atrial fibers was investigated under the treatment with aconitine, 3. 0 mmol/L K+ ,quinidine, ryanodine or Bay k 8644. All of these EADs possessed the following common characte...Early afterdepolarization (EAD) in mouse atrial fibers was investigated under the treatment with aconitine, 3. 0 mmol/L K+ ,quinidine, ryanodine or Bay k 8644. All of these EADs possessed the following common characteristics j all the parameters of EAD showed cycle length-dependence; take-off potential of the first triggered burst played an important role in the generation of the other parameters ; hyper-polarization of the triggered brust enhanced the end of EAD; and the second plateau response might be used as an indicator of the capability of EAD generation of myocardiac cell. All those EADs were inhibited or abolished by nifedipine, tetrodotoxin or lidocaine. Potassium channel activators, lemakalim, thalium ion, acetyl-choline or high potassium could also inhibit or abolish the EADs. It is suggested that the EADs induced by different agents may base on a common mechanism ; all currents contributing to the plateau phase of the action potential play an important role in the generation of EAD.展开更多
文摘Behavioral and psychological symptoms including agitation are common in dementia,and are associated with decreased quality of life,increased risk of institutionalization,and greater patient and caregiver distress.Pharmacological agents used for management of behavioral and psychological symptoms of dementia are limited by their tolerability,prompting a need for identifying efficacious and safe pharmacological treatments for managing agitation in dementia.The combination of dextromethorphan and quinidine sulfate is approved for pseudobulbar affect,and may be effective in managing agitation in dementia.A review of literature found only one randomized controlled trial that evaluated the use of dextromethorphan-quinidine for the management of agitation in dementia when compared to placebo.Data from this trial demonstrated that dextromethorphan-quinidine decreased agitation in dementia,and was well tolerated.Although promising,further research is needed before dextromethorphan-quinidine combination can be accepted as a standard treatment for agitation in dementia.
基金supported by the Natural Science Foundation of Jiangsu Province of China(Grant No.BK20160134 to LW and BK20191071 to CC)National Natural and Science Foundation of China(Grant No.81900295 to CC)Special Foundation for Clinical Science and Technology of Jiangsu Province(Grant No.BE2017754 to HWC).
文摘Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic background,the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes(iPSC-CMs)may help to reveal cell phenotype characteristics underlying different genetic variations.Here,to verify and compare the pathogenicity of mutations(SCN5A c.4213G>A and SCN1B c.590C>T)identified from two BrS patients,we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B,compared their structures and electrophysiology,and evaluated the safety of quinidine in patient-specific iPSC-derived CMs.Compared to the control group,BrS-CMs showed a significant reduction in sodium current,prolonged action potential duration,and varying degrees of decreased Vmax,but no structural difference.After applying different concentrations of quinidine,drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration(ETPC).The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.
基金Project supported by the National Natural Science Foundation of China.
文摘Early afterdepolarization (EAD) in mouse atrial fibers was investigated under the treatment with aconitine, 3. 0 mmol/L K+ ,quinidine, ryanodine or Bay k 8644. All of these EADs possessed the following common characteristics j all the parameters of EAD showed cycle length-dependence; take-off potential of the first triggered burst played an important role in the generation of the other parameters ; hyper-polarization of the triggered brust enhanced the end of EAD; and the second plateau response might be used as an indicator of the capability of EAD generation of myocardiac cell. All those EADs were inhibited or abolished by nifedipine, tetrodotoxin or lidocaine. Potassium channel activators, lemakalim, thalium ion, acetyl-choline or high potassium could also inhibit or abolish the EADs. It is suggested that the EADs induced by different agents may base on a common mechanism ; all currents contributing to the plateau phase of the action potential play an important role in the generation of EAD.
