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。     

双波长紫外分光光度法测定贝母中腺苷和胸苷的含量

将4种贝母的甲醇提取物经薄层色谱法粗分离后,直接用双波长紫外分光光度法测定其含量。结果表明,该方法线性关系好,腺苷和胸苷标准曲线的相关系数均为0.9999,同时也发现平贝、炉贝和伊贝中腺苷都占核苷总量60%以上,而浙贝中仅占约40%,提示贝母生药的抗凝血活性可能与贝母中核苷类化合物的种类和含量的差别有关。     

Lack of Major Effects on Mouse Brain Adenosine A1 Receptors of Oral Carbamazepine and Calcium Antagonists

Interaction with adenosine A1 receptors is a possible contributory mechanism to the anticonvulsant effects of carbamazepine (CBZ) and the dihydropyridine calcium antagonists. We measured the binding of [3H]cyclohexyladenosine to adenosine A1 receptors in mouse brain stem, cerebellum, and cortex after oral administration of nifedipine, nimodipine (NMD), and CBZ for 7 days and compared the results with binding in control mice. Equilibrium dissociation constant (Kd) and receptor numbers (Bmax) were calculated using Scatchard and saturation isotherm analyses. Mean Kds (SEM) in control brain stem, cerebellum, and cortex were 2.09 (0.31), 2.39 (0.2), and 3.12 (0.28) nM, respectively. Results of Bmax for the same areas were 188 (26), 280 (24), and 449 (54) fmol/mg protein. Nifedipine (p less than 0.005) and NMD (p less than 0.02) raised the Kd of A1 receptors only in the cerebellum, and CBZ increased cerebellar Bmax (p less than 0.05). These minor effects on A1 receptors in CF1 mice, when given in doses previously shown to have anticonvulsant properties in these animals, do not suggest that alteration in A1 receptor activity is an important mechanism for the anticonvulsant effects of these drugs.     

国产腺苷介入心肌灌注断层显像对心肌缺血的诊断价值

目的评价国产腺苷负荷心肌灌注断层显像对心肌缺血的诊断价值及腺苷试验的安全性。方法 102例临床疑冠心病患者行腺苷负荷/静息~(99)Tc~m-甲氧基异丁基异腈(MIBI)心肌灌注断层显像,其中70例显像1周内又行冠状动脉(简称冠脉)造影检查。腺苷按体重0.84 mg·kg~(-1)通过输液泵静脉双通路给药,对心肌灌注断层显像图作定性分析。结果 70例行冠脉造影者中正常31例,有冠脉狭窄病变者39例(单支病变19例,双支病变10例,3支病变10例);共检出病变血管69支,累及左前降支32支,左回旋支16支,右冠脉20支,左主干1支。腺苷负荷心肌灌注断层显像正常33例,心肌缺血37例,其对冠心病心肌缺血诊断的灵敏度为82.05%(32/39例),特异性为83.87%(26/31例),准确性为82.86%(58/70例),阳性预测值为86.49%(32/37例),阴性预测值为78.79%(26/33例)。对各病变血管检出的灵敏度为:左前降支75.00%(24/32支),左回旋支62.50%(10/16支),右冠脉80.00%(16/20支)。对单支、双支、3支血管病变诊断的灵敏度分别为68 42%、90.00%和100%。腺苷负荷心肌灌注断层显像对病变冠脉诊断总灵敏度为73.53%(50/68支),特异性96.48%(137/142支),准确性89.05%(187/210支),阳性预测值90.91%(50/55支),阴性预测值88.39%(137/155支)。腺苷试验不良反应轻,时间短,发生率为85.29%(87/102例)。结论国产腺苷负荷试验介入~(99)Tc~m-MIBI 心肌灌注断层显像安全可靠。     

外源性三磷酸腺苷对肾小管上皮细胞增殖的影响

观察外源性三磷酸腺苷（ＡＴＰ）对肾小管上皮细胞株ＬＬＣＰＫ１增殖的影响。方法通过测定３Ｈ－胸腺嘧啶掺入、细胞计数以及细胞内丝裂素活化蛋白激酶活性，并与表皮生长因子（ＥＧＦ）的作用比较。结果发现ＡＴＰ呈浓度依赖性促进细胞的ＤＮＡ合成，并可使细胞计数增加，同时激活细胞内的丝裂素活化蛋白激酶，其作用与ＥＧＦ相似。腺苷与ＡＴＰ有类似作用，但较弱。核苷酸转运蛋白抑制剂对４－硝基苯６－硫基甙并不能抑制ＡＴＰ及腺苷的作用。结论细胞外ＡＴＰ可促进肾小管上皮细胞增殖，并可增强ＥＧＦ的促增殖作用，这一作用可能是通过膜受体介导的细胞内丝裂素活化蛋白激酶活化而实现的     

三磷酸腺苷-氯化镁冷稀释血停搏液的实验研究及临床应用

用液体闪烁计数法测定离体再灌注兔心肌线粒体内４５Ｃａ２＋的放射性强度．观察三磷酸腺苷－氯化镁冷稀释血停搏液和冷稀释血停搏液对缺血再灌注兔心肌线粒体内４５Ｃａ２＋的影响．结果表明，在３０ｍｉｎ以内使用冷稀释血停搏液组兔心肌线粒体内４５Ｃａ２＋放射性强度高于三磷酸腺苷－氯化镁冷稀释血停搏液组（Ｐ＜０．０５），而６０ｍｉｎ时冷稀释血停搏液组的放射性强度稍高或接近于三磷酸腺苷－氯化镁冷稀释血停搏液组，差异无显著性（Ｐ＞０．０５）．在２７例心内直视手术中使用三磷酸腺苷－氯化镁冷稀释血停搏液均获良好效果．     

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。     

钾通道开放剂降低血管平滑肌细胞内游离钙浓度(英文)

目的:研究PCO—Pin,Nic,Lem及RP对VMSC内[Ca~(2 )]_i的改变及其可能机制。方法:VSMC加入Fura-2 AM 2.5μmol·L~(-1)37℃下孵育50min,[Ca~(2 )]_i用荧光分光光度计检测。结果:4种PCO能较弱地抑制K~ 30 mmol·L~(-1)诱导的[Ca~(2 )]_i增加,但明显抑制ATP 0.1mmol·L~(-1)诱导的[Ca~(2 )]_i峰相及持续相增加,且呈剂量依赖性。格列苯脲完全阻断Pin,Lem及RP的作用,只部分抑制Nic的作用。无钙液中先给4种PCO,能显著抑制ATP诱导的[Ca~(2 )]_i峰相增加。结论:4种PCO均抑制ATP诱导的[Ca~(2 )]_i增加,此作用与减少细胞外钙内流及细胞内钙释放有关。     

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。