Mechanism of over-activation in direct pathway mediated by dopamine D_1 receptor in rats with levodopa-induced dyskinesias

Objective To study the changes of prodynorphin （PDyn） gene expression and dopamine and cAMPregulated phosphoprotein of 32 kDa （DARPP-32） phosphorylation in rats with levodopa-induced dyskinesias （LID）, and to explore the mechanism of over-activation in direct pathway mediated by dopamine D1 receptor. Methods Parkinson＇s disease （PD） rats were received levodopa （10 mg/kg, i.p.） for 28 d to get the LID rats. According to the behavior scale, LID rats were divided into mild （n=8） and severe （n=16） groups. On day 29, 8 rats in severe LID group were given an acute intraperitoneal injection of MK-801 （0.1 mg/kg） 15 min before levodopa treatment （MK-801 group, n=8）. The normal rats received same course and dosage of levodopa as the control group （n=8）. Hybridization in situ was used to measure the expression of PDyn mRNA in striatum. Protein and mRNA levels of total DARPP-32 and phospho-Thr-34 DARPP-32 level were measured by immunoblotting and RT-PCR, respectively. Results The levels of PDyn mRNA and phospho-Thr-34 DARPP-32 increased significantly in LID rats compared with control rats （P〈0.01）, and they also increased markedly in severe LID group compared with mild group （P〈0.01）. Conclusion Phospho-Thr-34 DARPP-32 level was increased in LID rats, which contributed to the over-activation of direct pathway mediated by dopamine D1 receptor.

Potential protective role of ACE-inhibitors and AT1 receptor blockers against levodopa-induced dyskinesias:a retrospective case-control study

Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrostriatal pathway,thus affecting the development of levodopa-induced dyskinesia in Parkinson’s disease(PD).In the present study,we analyzed whether the use of this class of medication was associated with a reduced occurrence of levodopa-induced dyskinesia,using electronically-stored information of idiopathic PD patients enrolled at Novara University Hospital“Maggiore della Carità”.We conducted a retrospective case-control study identifying PD patients with dyskinesias(PwD;n=47)as cases.For each PwD we selected a non-dyskinetic control(NoD),nearly perfectly matched according to sex,Unified Parkinson’s Disease Rating Scale(UPDRS)part III score,and duration of antiparkinsonian treatment.Binary logistic regression was used to evaluate whether dyskinesias were associated with ACEi/ARBs use.Ninety-four PD patients were included,aged 72.18±9 years,with an average disease duration of 10.20±4.8 years and 9.04±4.9 years of antiparkinsonian treatment.The mean UPDRS part III score was 18.87±7.6 and the median HY stage was 2.In the NoD group,25(53.2%)were users and 22(46.8%)non-users of ACEi/ARBs.Conversely,in the PwD group,11(23.4%)were users and 36 non-users(76.6%)of this drug class(Pearson chi-square=8.824,P=0.003).Concerning general medication,there were no other statistically significant differences between groups.After controlling for tremor dominant phenotype,levodopa equivalent daily dose,HY 3-4,and disease duration,ACEi/ARBs use was a significant predictor of a lower occurrence of dyskinesia(OR=0.226,95%CI:0.080-0.636,P=0.005).Therefore,our study suggests that ACEi/ARBs may reduce levodopa-induced dyskinesia occurrence and,thanks to good tolerability and easy management,represent a feasible choice when dealing with the treatment of hypertension in PD patients.The study was approved by the Ethics Committee of Novara University Hospital“Maggiore della Carità”(CE 65/16)on July 27,2016.

Effect of Antisense FosB and CREB on the Expression of Prodynor- phin Gene in Rats with Levodopa-induced Dyskinesias

The effects of antisense FosB and CREB intra-striatum injection on the expression of prodynorphin （PDyn） gene in striatal neurons of Levodopa-induced dyskinesias （LID） rats with Parkinson disease （PD） were explored. PD model in rats was established by 6-OHDA microinjection stereotaxically. The rats were treated with chronic intermittent Levodopa celiac injection for 28 days to get the LID rats. Antisense FosB and cAMP response element-binding protein （CREB） were injected into striatum of all rats respectively. In situ hybridization was used to measure the changes in the expression of PDyn mRNA in striatum and behavior changes were observed. The results showed after administration of antisense FosB, abnormal involuntary movement （AIM） was decreased and the expression of PDyn mRNA in striatum was increased in LID rats as compared with sense FosB group （P〈0.01, respectively）. As compared with the control group, the expression of PDyn mRNA in striatum was decreased by antisense CREB-treated LID group （P〈0.0 l） and compared with sense CREB treated LID group, antisense CREB-treated LID group showed no changes in AIM scores and the expressions of PDyn mRNA （both P〉0.05）. In conclusion, FosB protein, which replaced the CREQ could regulate the expression of PDyn mRNA and play critical role in the pathogenesis of LID.

The role of nerve growth factor inducible protein B in the pathogenesis of levodopa-induced dyskinesias

Objective： To study the role of the expression of nerve growth factor inducible protein B gene （NGFI-B） in striatum in the pathogenesis of levodopa-induced dyskinesias （LID）. Methods： The rat model of LID was treated with SCH 23390（1 mg/kg ip,a dopamine D1 antagonist） and haloperidol （1 mg/kg ip,a dopanfme D2 antagonist） respectively. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to measure the expression of NGFI-B mRNA in stiiatam and the behavior changes were observed. Resuits： After treatment with SCH23390, abnormal involuntary movement （AIM） in LID rats was decreased （ P 〈 0.05 ） and the expression of NGFI-B mRNA in striatum did not change significantly. After treatment with haloperidol, the changes of AIM in LID rats were not significant and the expression of NGFI-B mRNA was increased significantly（ P 〈 0.01）. Conclusion： LID is associated with over-expression of NGFI-B in striatum. Abnormal activity in the direct pathway and the basal ganglia circuit could be involved in the occurrence of LID.

Kaempferol ameliorated levodopa-induced dyskinesia in experimental rats: A role of brain monoamines, cFOS, FosB, Parkin, Pdyn, TH, and p-JNK

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.

Cholecystokinin and cholecystokinin-A receptor: An attractive treatment strategy for biliary dyskinesia?

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.

Regional anesthesia in a patient with primary ciliary dyskinesia:A case report

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.

PRRT2基因突变相关疾病谱的临床特征及遗传学分析

目的回顾性分析总结10例PRRT2基因突变相关疾病谱患者的临床特点及遗传学特征。方法收集2020-07—2022-08就诊于首都医科大学宣武医院儿科的10例PRRT2基因相关癫痫患儿的临床特征、脑电图、头颅磁共振检查、基因特征及治疗结果,回顾性分析其特征。结果10例患儿均提示PRRT2基因杂合突变,其中3例为片段缺失,5例为移码突变,1例为剪接突变。10例患者中男5例,女5例,起病年龄4个月~10岁,其中7例诊断为自限性家族性婴儿癫痫(SFIE),1例诊断为发作性运动诱发性运动障碍(PKD),2例诊断为伴婴儿惊厥的发作性运动诱发性运动障碍(IC/PKD);5例存在PRRT2基因突变相关疾病家族史。7例口服奥卡西平治疗后发作控制,3例口服左乙拉西坦治疗后发作控制。结论PKD、SFIE及IC/PKD是一组与PRRT2基因突变相关的疾病谱,c.649dupC基因突变位点是热点突变位点。对于高度考虑SFIE、PKD及IC/PKD的患者,如全外显子测序未发现异常基因,需进一步行内含子及染色体微缺失/微重复检测,达到早期诊断及治疗的目的。

帕金森病并发异动症的风险因素分析及预测Nomogram模型建立

目的:分析帕金森病(PD)并发异动症的危险因素,并依此建立风险预测Nomogram模型。方法:回顾性分析2021年2月—2023年2月我院收治的324例PD病人的临床资料,按照2∶1比例将病人分为建模组(216例)和验证组(108例),根据是否发生异动症将病人分为异动症组和非异动症组。采用多因素Logistic回归分析法分析PD并发异动症的危险因素,并基于此构建风险预测Nomogram模型;采用Bootstrap法对Nomogram模型进行验证,并绘制校准曲线评价Nomogram模型的校准度,绘制受试者工作特征(ROC)曲线评价Nomogram模型的预测效能,绘制决策曲线验证模型的临床净获益率。结果:多因素Logistic回归分析可知,女性、运动不能-肌强直型、发病年龄较早、病程及左旋多巴使用时间较长、单日左旋多巴等效剂量较大均为PD病人并发异动症的危险因素(P<0.05)。根据上述影响因素构建Nomogram模型,运用Bootstrap法对Nomogram模型进行验证,建模组和验证组Nomogram模型的一致性指数(C-index)值分别为0.832,0.821,校准曲线和理想曲线拟合度均较好。建模组Nomogram模型预测PD病人并发异动症的ROC曲线下面积(AUC)为0.881[0.830,0.921],敏感度为84.13%,特异度为84.97%;验证组Nomogram模型预测PD病人并发异动症的AUC为0.870[0.792,0.927],敏感度为83.33%,特异度为84.62%。决策曲线显示,建模组风险阈值概率为4%~89%,有较高的净获益值;验证组风险阈值概率为2%~97%,有较高的净获益值。结论:女性、运动不能-肌强直型、发病年龄较早、病程及左旋多巴使用时间较长、单日左旋多巴等效剂量较大均为影响PD病人并发异动症的危险因素,据此构建的Nomogram预测模型具有良好的校准度、预测效能和临床应用效果。

Management of primary ciliary dyskinesia/Kartagener＇s syndrome in infertile male patients and current progress in defining the underlying genetic mechanism

Kartagener＇s syndrome （KS） is an autosomal recessive genetic disease accounting for approximately 50% of the cases of primary ciliary dyskinesia （PCD）. As it is accompanied by many complications, PCD/KS severely affects the patient＇s quality of life. Therapeutic approaches for PCD/KS aim to enhance prevention, facilitate rapid definitive diagnosis, avoid misdiagnosis, maintain active treatment, control infection and postpone the development of lesions. In male patients, sperm flagella may show impairment in or complete absence of the ability to swing, which ultimately results in male infertility. Assisted reproductive technology will certainly benefit such patients. For PCD/KS patients with completely immotile sperm, intracytoplasmic sperm injection may be very important and even indispensable. Considering the number of PCD/KS susceptibility genes and mutations that are being identified, more extensive genetic screening is indispensable in patients with these diseases. Moreover, further studies into the potential molecular mechanisms of these diseases are required. In this review, we summarize the available information on various aspects of this disease in order to delineate the therapeutic objectives more clearly, and clarify the efficacy of assisted reproductive technology as a means of treatment for patients with PCD/KS-associated infertility.

Compound Formula Rehmannia alleviates levodopainduced dyskinesia in Parkinson's disease

Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson＇s disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of Parkinson＇s disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of γ-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson＇s disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson＇s disease by modulating neurotransmitter signaling in the corpus striatum.

Clinical spectrum of primary ciliary dyskinesia in childhood

Although the triad of bronchiectasis, sinusitis and situs inversus was first described by Kartagener in 1933, the clinical spectrum of primary ciliary dyskinesia is still under investigation. Heterotaxy defects as well as upper and lower respiratory tract symptoms are the main manifestations in childhood. It is now recognized that situs inversus is encountered in only half of patients. The first lower respiratory symptoms may be present from infancy as neonatal respiratory distress. The most common lower airway manifestations are chronic wet cough, recurrent pneumonia and therapy resistant wheezing. Patients are at risk of developing bronchiectasis which may even be the presenting finding due to delayed diagnosis. Upper respiratory tract infections such as nasal congestion, nasal drainage and recurrent sinusitis as well as otologic manifestations such as otitis media or otorrhea with conductive hearing loss are also often encountered. It seems that the type of ciliary ultrastructure defects and the involved mutated genes are associated to some extent to the clinical profile. The disease, even in nowadays, is not recognized at an early age and the primary care clinician should have knowledge of its clinical spectrum in order to select appropriately the children who need further investigation for the diagnosis of this disorder.

Sphincter of Oddi dysfunction:Psychosocial distress correlates with manometric dyskinesia but not stenosis

AIM:To compare postcholecystectomy patients with Sphincter of Oddi(SO)dyskinesia and those with normal SO motility to determine the psychosocial distress,gender and objective clinical correlates of dyskinesia,and contrast these findings with comparisons between SO stenosis and normal SO motility.METHODS:Within a cohort of seventy-two consecutive postcholecystectomy patients with suspected SO dysfunction,manometric assessment identified subgroups with SO dyskinesia(n=33),SO stenosis(n=18)and normal SO motility(n=21).Each patient was categorized in terms of Milwaukee Type,sociodemographic status and the severity of stress-coping experiences.RESULTS:Logistic regression revealed that in combination certain psychological,sociodemographic and clinical variables significantly differentiated SO dyskinesia,but not SO stenosis,from normal SO function.Levels of psychosocial stress and of coping with this stress(i.e.anger suppressed more frequently and the use of significantly more psychological coping strategies)were highest among patients with SO dyskinesia,especially women.Higher levels of neuroticism(the tendency to stressproneness)further increased the likelihood of SO dyskinesia.CONCLUSION:A motility disturbance related to psychosocial distress may help to explain the finding of SO dyskinesia in some postcholecystectomy patients.

Adjunctive melatonin for tardive dyskinesia in patients with schizophrenia： a meta-analysis

背景:迟发性运动障碍(TD)的临床特征是异常不自主运动。TD具有严重的不可逆的致残性和社会功能损害。目的 :此荟萃分析基于随机对照试验(RCTs)文献系统评估褪黑素对精神分裂症患者迟发性运动障碍的临床疗效和安全性。方法 :两位独立评估者从以下数据库对相关的临床随机对照试验(RCT)文献进行检索(万方数据、中国知网(CNKI)、中国生物医学文摘数据库和PubM ed、PsycI NFO、Embase、Cochrane Library数据库),检索时间截止于2017年6月8日。以TD症状严重程度为主要结局指标,采用Rev Man 5.3版本进行统计分析,对RCTs的质量评估采用Cochrane风险评估偏倚和Jadad量表来评估各种偏倚的风险性。采用GRADE(Grades of Recommendation,Assessment,Development,and Evaluation)系统推荐分级方法对meta-分析结果的整体证据质量水平进行分级评价。结果 :最终筛选确定4个RCTs(n=130)。3个RCTs采用双盲法,1个RCT单盲,根据Cochrane风险评估偏倚和Jadad量表显示3个RCTs的疗效评估指标的证据质量被评定为"高质量"。与对照组相比,根据不自主运动量表(AIMS)评定褪黑素可改善TD严重程度(4个RCTs,n=130,加权平均差值(WMD):-1.52(95%CI:-3.24,0.20),p=0.08;I2=0%),但尚没有达到显著差异。根据等级方法,改善TD症状的meta分析结果的整体证据质量被评为"低",而关于不良反应和认知损害方面则数据太少。结论 :荟萃分析表明,褪黑素或可改善精神分裂症TD症状。但仍有待今后更高质量和更大样本的RCTs验证。

Targeted to medication-induced dyskinesia and tardive dyskinesia:A role of 5-HT_(1A) receptor

Objective To outline the recent progress in drug discovery for medication-induced dyskinesia(Parkinson disease,PD)and tardive diskinesia(schizophrenia)with emphasizing the role of 5-HT1A receptor.Methods Development of extrapyramidal syndrome(EPS)followed either chronic L-DOPA administration in PD(L-DOPA-induced dyskinesia,LID)or antipsychotic treatment in schizophrenia(Tardive dyskinesia,TD)remains a challenge in the clinical practice and drug discovery.In addition to the abnormal dopamine activity in the nigrostrial area that contributes to the LID or TD,recent information indicates that 5-HT1A receptor also plays an important role which is merging as promising target in treatment of LID or TD.Results l-Stepholidine(l-SPD),isolated from the Chinese herb Stephania,is known as a dual dopamine receptor agent(D1 receptor agonistic and D2 antagonistic activity).In addition,we further demonstrated that l-SPD binds to 5-HT1A receptor and exhibits a partial agonistic activity.In LID rat model,l-SPD not only attenuated the development of L-DOPA-induced dyskinesia(LID),but also relived the established LID.The effect of l-SPD on LID was completely blocked by pretreatment of 5-HT1A receptor antagonist,indicating the role of 5-HT1A receptor.Furthermore,we designed and synthesis a dual dopamine/5-HT1A receptor agonist MCL-135,which also exhibits a significant relief on LID while elicits its antiparkinsonian action.Conclusions 5-HT1A receptor plys an important role in the development of LID,targeted to dual dopamine/5-HT receptor may represent a promising strategy for drug design and discovery in LID and TD treatment.

CLINICAL OBSERVATION ON THE THERAPEUTIC EFFECT OF ACUPUNCTURE PLUS MANUAL REPOSITION FOR TREATMENT OF ACUTE LUMBAR VERTEBRAL ARTICULAR DYSKINESIA

Objective: To observe the therapeutic effect of acupuncture plus manual reposition for treatment of acute lumbar vertebral articular dyskinesia for choosing a better remedy. Methods: 66 cases of acute lumbar vertebral articular dyskinesia were randomly divided into acupuncture plus manual reposition group (treatment group, n=33) and routine manual reposition group (control group, n=33). Yaotong point was punctured, when, the patient was asked to move his or her waist simultaneously. Results: After one session of treatment, of the two 33 cases in treatment and control groups, 28 (84.85%) and 20 (60.61%) were cured, 4 (12.12%) and 9 (27.27%) were improved, and 1 (3.03%) and 4 (12.12%) failed in the treatment. The therapeutic effect of treatment group was significantly superior to that of control group (P<0.05). Conclusion: Acupuncture combined with manual reposition is apparently superior to simple routine manual reposition in relieving acute lumbar vertebral articular dyskinesia.

Paroxysmal kinesigenic dyskinesia presenting with transient involuntary twitching movements involving right leg in a 24-year-old man responding well to topiramate

Paroxysmal kinesigenic dyskinesia(PKD)is presented as a short paroxysmal attack of focal or generalized involuntary movement.The most common treatments for PKD are carbamazepine and phenytoin.Though the cases of clinically diagnosed PKD with a good response to topiramate have been already reported,this patient was unique in several ways.Here,we reported the case of a 24-year-old patient with PKD for one year,and described the pathogenesis of PKD.

The effects of L-Dopa and <i>N</i>-(alpha-linolenoyl) tyrosine on 6-OH-DA lesions on dopamine level and activity, dyskinesia and homocysteinemia in rats

The three major issues in L-DOPA therapy for Parkinson are: 1) rapid tolerance;2) induced dyskinesia;3) hyperhomocysteinemia. The newly synthesized molecule, which is an amide bond molecule composed of L-tyrosine and alphalinolenic acid, i.e., N-(alpha-linolenoyl) tyrosine (NLT), represents a new class of molecules that combines essential amino acids with essential fatty acids. This study demonstrates that acute administration of NLT results in prolonged increase of the brain dopamine level, and that this molecule is able to overcome the three major problems associated with Parkinson’s L-DOPA therapy: it is able to elevate brain dopamine levels and increase activity, without inducing tolerance, dyskinesia or hyperhomocysteinemia.

Decision-making patterns in managing children with suspected biliary dyskinesia

AIM To explore and to analyze the patterns in decisionmaking by pediatric gastroenterologists in managing a child with a suspected diagnosis of functional gallbladder disorder(FGBD).METHODS The questionnaire survey included a case history with right upper quadrant pain and was sent to pediatric gastroenterologists worldwide via an internet list server called the PEDGI Bulletin Board.RESULTS Differences in decision-making among respondents in managing this case were observed at each level of investigations and management.Cholecystokinin-scintigraphy scan(CCK-CS) was the most common investigation followed by an endoscopy.A proton pump inhibitor was most commonly prescribed treating the condition.The majority of respondents considered a referral for a surgical evaluation when CCK-CS showed a decreased gallbladder ejection fraction(GBEF) value with biliary-type pain during CCK injection.CONCLUSION CCK infusion rate in CCK-CS-CS and GBEF cut-off limits were inconsistent throughout practices.The criteria for a referral to a surgeon were not uniform from one practitioner to another.A multidisciplinary team approach with pediatric gastroenterologists and surgeons is required guide the decision-making managing a child with suspected FGBD.

MADOPAR-INDUCED DYSKINESIA IN 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) HEMIPARKINSONIAN MONKEY MODEL

Infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the right common carotid artery produced hemiparkinsonian syndrome on contralateral limbs in 5 rhesus monkeys. The hemiparkinsonian syndrome produced responded to madopar medication and the circling motion changed from toward the MPTP-treated side to away from the MPTP-treated side. Long term use of madopar developed a peak-dose dyskinesia of the face and limbs at the contralateral side. The toxic effect of MPTP was confirmed biochemically by reduction of nigrostriatal DA and histologically by degeneration of nigral neurons on the MPTP-treated side. It is concluded that this hemiparkinsonian monkey model will be of value in the elucidation of the neural mechanism underlying L-DOPA or DA agonists induced dyskinesia in Parkinson’s disease and in the search for newer methods of treatment which would produce less dyskinesia.