Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson’s disease: A single-arm,open-label,prospective, multicenter study

Background: Gait disorders are common in Parkinson’s disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A_2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A_2A receptor antagonist with benefits for motor complications associated with Parkinson’s disease.

Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.

Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.

Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.

Trial registration: UMIN-CTR (UMIN000020288).     

腺苷与异丙酚预处理对犬心肌缺血再灌注损伤的保护作用

目的探讨腺苷与异丙酚预处理对犬心肌缺血再灌注损伤的保护作用。方法 21只杂种犬,雌雄不拘,随机分为3组(n=7):缺血再灌注组(A组)、异丙酚预处理组(B组)、异丙酚与腺苷联合预处理组(C组)。A组冠状动脉的左前降支结扎60min后松开结扎,再灌注:120min;B组缺血前30min经静脉以5．6mg·kg-1·h-1速率持续泵注异丙酚30min;C组缺血前10min经主动脉根部一次性注入腺苷(10mmol·L-1,10ml),其余处理同B组。记录心脏血液动力学指标,并行节段性室壁运动评分(RWMS)。结果缺血即刻出现了缺血性心电图的变化。与基础值比较,A组缺血期及再灌注期 LVEDP升高,CO、SV、LVEF、CPP、RPP降低,再灌注期MAP降低,HR减慢,B、C组上述缺血再灌注诱导的血液动力学变化减弱,A组缺血期及再灌注期RWMS增加,但B、C组缺血期RWMS低于A组(P< 0．05或0．01)。结论异丙酚预处理对犬心肌缺血再灌注损伤有一定的保护作用,腺苷预处理并未增强其保护作用。     

ATP下鼻甲注射治疗药物性鼻炎的价值

目的 探讨ATP下鼻甲注射治疗药物性鼻炎的价值,并对ATP治疗药物性鼻炎的机理进行分析。方法 对80例采用ATP下鼻甲注射治疗(ATP组)与40例采用激光治疗(激光组)作疗效比较。结果 ATP组有效率(95％),与激光组(100％),疗效相当,无显著性差异(P>0.05)。结论ATP下鼻甲注射治疗药物性鼻炎疗效佳,起效快,痛苦小,简便易行,费用低廉,且无毒、副作用,值得推广。     

腺苷A1受体诱导预处理延迟效应对供心保存的影响及机制探讨

目的　探讨腺苷A1受体激动剂预处理延迟效应对保存大鼠心脏的影响及其机制。方法　Wistar大鼠随机分为 8组 ,A、C组以高选择性腺苷A1受体激动剂 (CCPA)预处理 ;D、E、F组在CCPA预处理前分别注射锰 超氧化物歧化酶 (Mn SOD)反义、有意义、错配寡核苷酸 (ODN) ;B、G组注射生理盐水 ,H组只注射反义寡核苷酸。 2 4h后 ,A、B组用 4℃St.Thomas液保存 4h ,复灌 1h ,而另 6组采取低温缺血 3h ,复灌 1h。观测心功能、磷酸肌酸激酶 (CK mb)、三磷酸腺苷 (ATP)含量等。结果　A组左室内压上升与下降最大速率恢复率 (±dp/dtmax,% )为 6 2 .83± 17.2 7,6 6 .81± 18.99,心肌ATP含量 (10 3 μmol/g)为3.6 7± 1.4 2 ;而B组分别为 4 0 .4 1± 18.2 9,4 4 .70± 2 5 .14 ,1.4 6± 0 .5 4 ;A组均明显高于B组 ,差异均有显著性 (P <0 .0 1orP <0 .0 5 )。C组±dp/dtmax恢复率、ATP、Mn SOD活性均明显高于D、G、H组 (P <0 .0 1orP <0 .0 5 ) ,而与E、F组比较 ,差异无显著性。结论　腺苷A1受体激动剂能诱导预处理的延迟效应 ,改善离体大鼠心脏的保存效果 ,而该效应与Mn SOD的高表达有关。     

腺苷对突触体^45Ca摄取的抑制作用

用同位素标记~(15)Ca法测定大鼠突触体内游离钙的浓度,探讨了腺苷对高钾、N-甲基-D-天冬氨酸(NMDA)谷氨酸(Glu)等刺激所致的Ca~(2 )内流增加的影响。结果发现腺苷在10nmol/L～0.1μmol/L范围内对高钾、NMDA、Glu等刺激所致的Ca~(2 )内流有抑制作用,并呈剂量依赖关系,最大抑制率分别为41.68±7.68％、31.32±6.17％、37.52±2.29％。这可能是腺苷对缺血性脑损伤保护作用的机理。     

体外循环对瓣膜置换术病人血细胞胰岛素受体和红细胞ATP含量的影响

目的：观察体外循环（ＣＰＢ）对１０例瓣膜置换术病人全血细胞胰岛素受体和红细胞ＡＴＰ含量的影响。方法：利用放射配体结合试验，测定全血细胞胰岛素受体密度和亲和力；用高效液相色谱法测定红细胞ＡＴＰ含量，同时监测血糖和胰岛素浓度。结果：转流３０分钟，血细胞高亲和胰岛素受体（Ｒ１）密度明显增加（Ｐ＜０．０１），亲和力（Ｋ１）明显降低（Ｐ＜０．０１），低亲和胰岛素受体（Ｒ２）密度也明显增加（Ｐ＜０．０１），但亲和力（Ｋ２）变化不大（Ｐ＞０．０５）；停机３０分钟，上述变化有所恢复，但未到转流前的水平。转流３０分钟红细胞ＡＴＰ含量明显降低（Ｐ＜０．０１），并持续到停机后３０分钟，同时伴随血糖明显升高（Ｐ＜０．０１），胰岛素／血糖比值明显降低（Ｐ＜０．０１）。结论：ＣＰＢ可致血细胞胰岛素受体密度增加而亲和力下降，以及红细胞ＡＴＰ含量下降。     

Adenosine protects ultrastrueture of isolated rat lungs against fat emulsion injury

In isolated rat lungs subjected to fat emulsion damage, a model simulating adult respiratory distress syndrome, we have previously reported that adenosine (ADO) reduces pulmonary vascular resistance (PVR) and the fluid filtration rate (FFR). In the present study the aim was to examine morphologically this effect of ADO. Two groups of isolated rat lungs were subjected to the injury. Marked and significant differences were found between the groups; in lungs not given ADO, FFR and airway pressure were higher and, as evaluated by electron microscopy, the endothelial lining was thin and partly disrupted. The epithelial cells of the alveolar walls were also partly disrupted and the alveolar septa were split enclosing interstitial edema. In lungs receiving ADO from the onset of exposure to fat emulsion, FFR was lower and ultrastructure did not differ from non–injured non–treated controls perfused for the same length of time.     

卡介苗配用腺苷接种提高巨噬细胞抗结核杆菌效能的研究

目的　通过腺苷 (ADO)改善卡介苗 (BCG)初次免疫接种效果 ,提高巨噬细胞抗结核杆菌毒力株效能。方法　将BALB/C小鼠随机分BCG组、ADO组和对照组。对BCG、ADO两组分别一次性皮内注射卡介苗 0 1ml。对ADO组腹腔注射ADO 30mg/(kg·d) ,对BCG组、对照组腹腔注射生理盐水 0 1ml/d ,共 5d。 6周后 ,三组均经血管接种人型结核分枝杆菌标准毒力株 1× 10 6CFU ,BCG组、ADO组于结核杆菌感染后第 10、2 0天和 30天分批取材 ,对照组于第 30天取材。将肺、脾用多聚甲醛固定 ,石蜡包埋 ,HE染色与抗酸染色 ,进行原位细胞凋亡检测。结果　对照组结核杆菌感染后第30天 ,肺组织大部分实变 ,以中性粒细胞浸润为主 ,结核结节多 ,肺实变与肺泡隔重度增宽处弥漫分布大量菌体 ;BCG组于感染后第 10～ 30天肺泡隔增宽 ,逐渐加重至肺大部分实变 ,间质内以淋巴细胞浸润为主 ,结核结节较少 ,肺内大量菌体 ;而ADO组肺实变和肺泡隔重度增宽的面积较小 ,间质内以单核细胞浸润为主 ,结核结节很少 ,肺内菌体明显减少。结论　ADO促进BCG诱导的免疫记忆性反应中能引起单核 巨噬细胞的数量增多和杀菌能力的增强     

Epileptogenic actions of xanthines in relation to their affinities for adenosine A1 receptors in CA3 neurons of hippocampal slices (guinea pig)

In order to analyze the epileptogenic mechanisms of caffaine and related xanthines, putative effects of these drugs were studied on adenosine receptors of CA3 neurons in hippocampal slices. Epileptogenic concentrations of different xanthine derivatives strongly correlated with their affinities for the inhibitory A₁ adenosine receptor subtype. The A₁ receptor agonists adenosine and R-PIA reversibly depressed xanthine-induced epileptic activity without effects on the resting membrane potential or on spontaneously occuring action potentials. These findings suggest that the epileptogenic potency of xanthines is primarily due to the blockade of the A₁ receptors through an abnormal rise of intracellular cAMP and to the excessive transmembrane calcium fluxes underlying paroxysmal depolarization shifts.     

红细胞同工酶ADA－EAP一AK_1同步电泳分型方法的建立

综合、改良了分别分型的方法，建立了红细胞同工酶ＡＤＡ一ＥＡＰ一ＡＫ１同步电泳分型方法，为ＡＤＡ，ＥＡＰ和ＡＫ１３种红细胞同工酶在法医学鉴定中更广泛的应用，提供了一种可靠、经济、实用的方法。