Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are scarce.Flavonoids r...Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are scarce.Flavonoids reported their neuroprotective activity by ameliorating acetylcholinesterase,monoamine oxidase,and neuroinflammation.Kaempferol is anotherflavonoid bearing these potentials.Aim:To evaluate neuroprotective activity of kaempferol in dyskinetic rats.Methods:PD was developed in Sprague-Dawley rats by injecting combination of L-ascorbic acid(10µL)+6-OHDA(12µg)in medial forebrain bundle to induce neuronal damage in substantial nigra(SNr).LID was induced by administrating combination of L-dopa(20 mg/kg)+benserazide HCl(5 mg/kg)for 42 days.Rats were concomitantly treated with amantadine(40 mg/kg)or kaempferol(25,50,and 100 mg/kg,p.o.).Results:Kaempferol(50 and 100 mg/kg)markedly(p<0.05)inhibited LID-induced abnormal involuntary movements(AIMs)and alternation in motor function.Kaempferol administration considerably(p<0.05)inhibited reduced mitochondrial complex activities,serotonin and dopamine levels,Bcl-2,and Tyrosine hydroxylase protein expressions in SNr.Additionally,kaempferol considerably(p<0.05)attenuated increased cFOS,FosB,Parkin,and Pdyn mRNAs expressions,Bax,cleaved caspase-3,caspase-3,and pJNK proteins levels;DOPAC and 5-HIAA levels in SNr.A positive correlation was reported between cFOS,FosB,Parkin,Pdyn,apoptosis,and TH with AIMs.Conclusion:Kaempferol effectively attenuated L-dopa-induced AIMs and dyskinesia via amelioration of alterations in cFOS,FosB,Parkin,Pdyn,Tyrosine hydroxylase,and apoptosis in the brain SNr.展开更多
Biliary dyskinesia is a relatively common gastrointestinal disease that is increas-ing in incidence as living standards improve.However,its underlying pathogenesis remains unclear,hindering the development of therapeu...Biliary dyskinesia is a relatively common gastrointestinal disease that is increas-ing in incidence as living standards improve.However,its underlying pathogenesis remains unclear,hindering the development of therapeutic drugs.Recently,“Expression and functional study of cholecystokinin-A receptors on the interstitial Cajal-like cells of the guinea pig common bile duct”demonstrated that cholecystokinin(CCK)regulates the contractile function of the common bile duct through interaction with the CCK-A receptor in interstitial Cajal-like cells,contributing to improving the academic understanding of biliary tract dynamics and providing emerging directions for the pathogenesis and clinical management of biliary dyskinesia.This letter provides a brief overview of the role of CCK and CCK-A receptors in biliary dyskinesia from the perspective of animal experiments and clinical studies,and discusses prospects and challenges for the clinical application of CCK and CCK-A receptors as potential therapeutic targets.展开更多
BACKGROUND Primary ciliary dyskinesia(PCD)is an inherited autosomal-recessive disorder of impaired mucociliary clearance characterized by chronic respiratory diseases,otolaryngological diseases,central nervous system ...BACKGROUND Primary ciliary dyskinesia(PCD)is an inherited autosomal-recessive disorder of impaired mucociliary clearance characterized by chronic respiratory diseases,otolaryngological diseases,central nervous system abnormalities,reproductive system abnormalities,and cardiac function abnormalities.General anesthesia in these patients is associated with a higher incidence of respiratory complications than in patients without the disease.CASE SUMMARY A 16-year-old male patient was referred to the emergency room complaining of right ankle pain due to distal tibiofibular fracture.Three years prior,he had been diagnosed with PCD.At that time,he had experienced several episodes of pneumonia,sinusitis,and chronic middle ear infections,for which he underwent surgical interventions.At the current admission,he presented with cough and sputum but no other respiratory symptoms.A chest computed tomography scan revealed centrilobular ground-glass opacities in both lower lobes and a calcified nodule in the left lower lobe.For the surgical procedure and postoperative pain management,combined spinal-epidural anesthesia was employed.The patient’s postoperative pain score was measured by the numerical rating scale(NRS).On the day of surgery,his NRS was 5 points.By the second postoperative day,the NRS score had decreased to 2–3 points.The epidural catheter was removed on the fourth day following the operation.The patient was subsequently discharged no respiratory complications.CONCLUSION We performed combined spinal-epidural anesthesia in a patient with PCD.The patient experienced no additional respiratory complications and was discharged with a low NRS score for pain.展开更多
BACKGROUND Tardive dyskinesia(TD)is a serious and disabling movement disorder;it impairs social function and quality of life and increases the mortality rate.TD is usually induced by the use of antipsychotic drugs;how...BACKGROUND Tardive dyskinesia(TD)is a serious and disabling movement disorder;it impairs social function and quality of life and increases the mortality rate.TD is usually induced by the use of antipsychotic drugs;however,the underlying mechanism remains unclear.Pharmacotherapy of TD includes cholinergic drugs,benzodiazepines,ginkgo biloba extract(GBE),antioxidants,amantadine,propanolol,botulinum toxin,valbenazine,and deutetrabenazine,whereas the non-pharmacotherapy approach includes modified electroconvulsive therapy(MECT)and deep brain stimulation.We successfully treated a chronic schizophrenia patient with comorbid long-term severe TD using deutetrabenazine,clozapine,and MECT.CASE SUMMARY A 69-year-old woman who was diagnosed as having schizophrenia 16 years ago developed severe TD after 6-mo prescription of risperidone oral solution.Her TD symptoms did not resolve despite various treatments,such as GBE,vitamin E,trihexyphenidyl,promethazine,benzodiazepines,and switching to quetiapine and olanzapine.After admission,she was given deutetrabenazine 6 mg bid.Her buccal tremor was slightly resolved 3 d later;however,her tongue remained protruded and could not be retracted.Quetiapine was switched to clozapine on day 4,and the buccal tremor remarkably resolved,and the tongue could be retracted into the mouth from day 6 onward.After three sessions of MECT,the buccal tremor resolved further.Since then,she has been able to take a semifluid diet,and her quality of life improved remarkably during 6 mo of follow-up.CONCLUSION TD is a serious condition which could be caused by antipsychotic medications;however,the best strategy against TD is prevention and monitoring during using antipsychotics.For patients with TD caused by antipsychotic medication use,multiple measures should be considered like switching to clozapine,adjunction with deutetrabenazine,or even MECT.展开更多
Striatal interneurons play a key role in modulating striatal-dependent behaviors,including motor activity and reward and emotional processing.Interneurons not only provide modulation to the basal ganglia circuitry und...Striatal interneurons play a key role in modulating striatal-dependent behaviors,including motor activity and reward and emotional processing.Interneurons not only provide modulation to the basal ganglia circuitry under homeostasis but are also involved in changes to plasticity and adaptation during disease conditions such as Parkinson's or Huntington's disease.This review aims to summarize recent findings regarding the role of striatal cholinergic and GABAergic interneurons in providing circuit modulation to the basal ganglia in both homeostatic and disease conditions.In addition to direct circuit modulation,striatal interneurons have also been shown to provide trophic support to maintain neuron populations in adulthood.We discuss this interesting and novel role of striatal interneurons,with a focus on the maintenance of adult dopaminergic neurons from interneuronderived sonic-hedgehog.展开更多
文摘Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are scarce.Flavonoids reported their neuroprotective activity by ameliorating acetylcholinesterase,monoamine oxidase,and neuroinflammation.Kaempferol is anotherflavonoid bearing these potentials.Aim:To evaluate neuroprotective activity of kaempferol in dyskinetic rats.Methods:PD was developed in Sprague-Dawley rats by injecting combination of L-ascorbic acid(10µL)+6-OHDA(12µg)in medial forebrain bundle to induce neuronal damage in substantial nigra(SNr).LID was induced by administrating combination of L-dopa(20 mg/kg)+benserazide HCl(5 mg/kg)for 42 days.Rats were concomitantly treated with amantadine(40 mg/kg)or kaempferol(25,50,and 100 mg/kg,p.o.).Results:Kaempferol(50 and 100 mg/kg)markedly(p<0.05)inhibited LID-induced abnormal involuntary movements(AIMs)and alternation in motor function.Kaempferol administration considerably(p<0.05)inhibited reduced mitochondrial complex activities,serotonin and dopamine levels,Bcl-2,and Tyrosine hydroxylase protein expressions in SNr.Additionally,kaempferol considerably(p<0.05)attenuated increased cFOS,FosB,Parkin,and Pdyn mRNAs expressions,Bax,cleaved caspase-3,caspase-3,and pJNK proteins levels;DOPAC and 5-HIAA levels in SNr.A positive correlation was reported between cFOS,FosB,Parkin,Pdyn,apoptosis,and TH with AIMs.Conclusion:Kaempferol effectively attenuated L-dopa-induced AIMs and dyskinesia via amelioration of alterations in cFOS,FosB,Parkin,Pdyn,Tyrosine hydroxylase,and apoptosis in the brain SNr.
文摘Biliary dyskinesia is a relatively common gastrointestinal disease that is increas-ing in incidence as living standards improve.However,its underlying pathogenesis remains unclear,hindering the development of therapeutic drugs.Recently,“Expression and functional study of cholecystokinin-A receptors on the interstitial Cajal-like cells of the guinea pig common bile duct”demonstrated that cholecystokinin(CCK)regulates the contractile function of the common bile duct through interaction with the CCK-A receptor in interstitial Cajal-like cells,contributing to improving the academic understanding of biliary tract dynamics and providing emerging directions for the pathogenesis and clinical management of biliary dyskinesia.This letter provides a brief overview of the role of CCK and CCK-A receptors in biliary dyskinesia from the perspective of animal experiments and clinical studies,and discusses prospects and challenges for the clinical application of CCK and CCK-A receptors as potential therapeutic targets.
文摘BACKGROUND Primary ciliary dyskinesia(PCD)is an inherited autosomal-recessive disorder of impaired mucociliary clearance characterized by chronic respiratory diseases,otolaryngological diseases,central nervous system abnormalities,reproductive system abnormalities,and cardiac function abnormalities.General anesthesia in these patients is associated with a higher incidence of respiratory complications than in patients without the disease.CASE SUMMARY A 16-year-old male patient was referred to the emergency room complaining of right ankle pain due to distal tibiofibular fracture.Three years prior,he had been diagnosed with PCD.At that time,he had experienced several episodes of pneumonia,sinusitis,and chronic middle ear infections,for which he underwent surgical interventions.At the current admission,he presented with cough and sputum but no other respiratory symptoms.A chest computed tomography scan revealed centrilobular ground-glass opacities in both lower lobes and a calcified nodule in the left lower lobe.For the surgical procedure and postoperative pain management,combined spinal-epidural anesthesia was employed.The patient’s postoperative pain score was measured by the numerical rating scale(NRS).On the day of surgery,his NRS was 5 points.By the second postoperative day,the NRS score had decreased to 2–3 points.The epidural catheter was removed on the fourth day following the operation.The patient was subsequently discharged no respiratory complications.CONCLUSION We performed combined spinal-epidural anesthesia in a patient with PCD.The patient experienced no additional respiratory complications and was discharged with a low NRS score for pain.
基金Science and Technology Program of Huzhou City,No.2023GYB32.
文摘BACKGROUND Tardive dyskinesia(TD)is a serious and disabling movement disorder;it impairs social function and quality of life and increases the mortality rate.TD is usually induced by the use of antipsychotic drugs;however,the underlying mechanism remains unclear.Pharmacotherapy of TD includes cholinergic drugs,benzodiazepines,ginkgo biloba extract(GBE),antioxidants,amantadine,propanolol,botulinum toxin,valbenazine,and deutetrabenazine,whereas the non-pharmacotherapy approach includes modified electroconvulsive therapy(MECT)and deep brain stimulation.We successfully treated a chronic schizophrenia patient with comorbid long-term severe TD using deutetrabenazine,clozapine,and MECT.CASE SUMMARY A 69-year-old woman who was diagnosed as having schizophrenia 16 years ago developed severe TD after 6-mo prescription of risperidone oral solution.Her TD symptoms did not resolve despite various treatments,such as GBE,vitamin E,trihexyphenidyl,promethazine,benzodiazepines,and switching to quetiapine and olanzapine.After admission,she was given deutetrabenazine 6 mg bid.Her buccal tremor was slightly resolved 3 d later;however,her tongue remained protruded and could not be retracted.Quetiapine was switched to clozapine on day 4,and the buccal tremor remarkably resolved,and the tongue could be retracted into the mouth from day 6 onward.After three sessions of MECT,the buccal tremor resolved further.Since then,she has been able to take a semifluid diet,and her quality of life improved remarkably during 6 mo of follow-up.CONCLUSION TD is a serious condition which could be caused by antipsychotic medications;however,the best strategy against TD is prevention and monitoring during using antipsychotics.For patients with TD caused by antipsychotic medication use,multiple measures should be considered like switching to clozapine,adjunction with deutetrabenazine,or even MECT.
文摘目的:探讨脑白质病变(white matter lesions,WML)对帕金森病(Parkinson’s disease,PD)患者运动症状、认知功能和情绪的影响。方法:纳入2018年1月至2023年12月就诊于安徽医科大学第二附属医院神经内科PD患者123例,应用年龄相关的白质改变(age-related white matter changes,ARWMC)量表评估患者头颅MRI影像学的脑白质病变程度,根据评分结果将患者分为轻度WML组(46例),中重度WML组(77例);使用帕金森病统一评定量表第三部分、Hoehn&Yahr(H-Y)分级量表评定运动症状及疾病严重程度,简易精神状态检查(mini-mental state examination,MMSE)评估PD的认知功能,汉密尔顿抑郁量表,汉密尔顿焦虑量表评定情绪状态,Barthel指数评定患者日常生活功能状态。比较两组患者的运动症状、认知及情绪评分等差异,应用Logistic回归分析PD患者的WML与临床症状的关系。结果:中重度WML组的高血压发生率(41.6%vs.23.9%,P<0.05)高于轻度WML组。中重度WML组的H-Y分级高于轻度WML组[2.5(1.5,3.0)vs.2.0(1.5,2.5),P<0.05],UPDRS-Ⅲ评分高于轻度WML组[(34.0±16.5)vs.(24.09±11.04),P<0.01]。此外,中重度WML组的MMSE评分低于轻度WML组[24.0(18.5,27.0)vs.26.0(23.8,27.0),P<0.01],Barthel得分亦低于轻度WML组[(77.4±17.4)vs.(83.5±11.7),P<0.05],差异有统计学意义。相关分析显示,ARWMC总分与HY及UPDRS-Ⅲ得分呈正相关,与年龄亦呈正相关。ARWMC总分与MMSE得分及Barthel评分呈负相关。Logistic回归分析显示,重度WML损害与认知障碍有相关性(回归系数β=1.072,95%CI=1.078~7.918,P=0.035)。结论:WML与PD运动障碍、认知功能损害及生活质量下降相关。
文摘Striatal interneurons play a key role in modulating striatal-dependent behaviors,including motor activity and reward and emotional processing.Interneurons not only provide modulation to the basal ganglia circuitry under homeostasis but are also involved in changes to plasticity and adaptation during disease conditions such as Parkinson's or Huntington's disease.This review aims to summarize recent findings regarding the role of striatal cholinergic and GABAergic interneurons in providing circuit modulation to the basal ganglia in both homeostatic and disease conditions.In addition to direct circuit modulation,striatal interneurons have also been shown to provide trophic support to maintain neuron populations in adulthood.We discuss this interesting and novel role of striatal interneurons,with a focus on the maintenance of adult dopaminergic neurons from interneuronderived sonic-hedgehog.
