盐酸哌甲酯控释片治疗注意缺陷多动障碍不同亚型疗效比较

[摘要]目的：比较盐酸哌甲酯控释片（专注达）治疗注意缺陷为主型、冲动-多动为主型以及混合型注意缺陷多动障碍（ADHD）患儿的疗效。方法：选取2017年7月至2018年8月我院诊治的ADHD患儿100例,根据DSM-Ⅳ中ADHD诊断标准分为三组,分别为ADHD-I组（注意缺陷为主型）33例、ADHD-HI组（冲动-多动为主型）33例和ADHD-C组（混合型）34例。三组患儿均采用盐酸哌甲酯控释片治疗,18 mg/d,疗程为6周。采用SNAP-Ⅳ父母评定量表及Conners父母症状评价量表评价疗效,观察并比较三组患儿的治疗效果及不良反应情况。结果：治疗后三组患儿在SNAP-Ⅳ和Conners量表中各指标均得到显著改善,且ADHD-HI组患儿改善幅度大于ADHD-I组和ADHD-C组（P均<0.05）,而ADHD-I组和ADHD-C组改善幅度比较差异无统计学意义（P均>0.05）。ADHD-HI组患儿总有效率84.85%（28/33）,较ADHD-I组的66.67%（22/33）和ADHD-C组的73.53%（25/34）高（P均<0.05）。三组不良反应发生率的比较差异无统计学意义（P>0.05）。结论：盐酸哌甲酯控释片治疗ADHD患儿有显著疗效,但不同亚型间的疗效存在差异。     

哌甲酯治疗汉族儿童注意缺陷多动障碍疗效与GRIN2B基因多态性的关系

目的:探讨N-甲基-D-天冬氨酸受体2B亚单位基因(GRIN2B)rs1806201位点和rs1805247位点多态性与哌甲酯治疗汉族注意缺陷多动障碍(ADHD)患儿疗效的关系。方法:2017年1月至2019年1月驻马店市中心医院收治的100例ADHD患儿作为研究对象,进行2~4周的哌甲酯开放剂量治疗,获得最佳治疗反应。采用注意缺陷多动障碍诊断量表父母版(ADHDDS-P)评估ADHD症状。根据治疗前后量表评分,将疗效分为缓解、有效和无效。用TaqMan SNP基因分型技术检测GRIN2B基因rs1806201位点和rs1805247位点多态性。结果:100例患儿治疗后缓解40例,有效25例,无效35例。GRIN2B基因rs1806201位点TT型和CT型患儿治疗效果优于CC型患儿(P<0.05)。而rs1805247位点不同基因型患儿治疗效果的比较差异无统计学意义(P>0.05)。rs1806201位点TT和CT基因型患儿治疗后ADHDDS-P量表注意力缺陷评分、多动冲动评分和总分的减分值均高于CC型患儿(P<0.05),而rs1805247位点不同基因型患儿ADHDDS-P量表减分值比较差异无统计学意义(P>0.05)。结论:GRIN2B基因rs1806201位点多态性与哌甲酯治疗效果有关,而GRIN2B基因rs1805247位点多态性与哌甲酯治疗效果无关。GRIN2B基因rs1806201位点TT型和CT型ADHD患儿对哌甲酯的药物反应优于CC基因型患儿。     

哌甲酯与托莫西汀在注意缺陷多动障碍患儿治疗中的疗效及安全性分析

目的：探究哌甲酯与托莫西汀在注意缺陷多动障碍患儿治疗中的疗效及安全性。方法：遴选福州儿童医院2019年6月至2021年3月期间收治的90例注意缺陷多动障碍患儿视为探究对象，以随机数字法将其划分成为相等例数(n=45)的对照组、观察组，对照组以单一哌甲酯治疗，观察组以哌甲酯联合托莫西汀治疗，对比两组患者的观察指标：疗效、药物不良反应发生率、Conners儿童行为问卷评分。结果：治疗前两组患者的Conners儿童行为问卷评分无显著差异(P>0.05),治疗后，观察组患儿的Conners儿童行为问卷评分较对照组低(P<0.05);观察组患儿的药物不良反应发生率与对照组相比无显著差异(χ²=0.345,P=0.557);观察组患儿的疗效97.78%较对照组80.00%更高(χ²=7.200,P=0.007)。结论：注意缺陷多动障碍患儿予以哌甲酯联合托莫西汀治疗可提升疗效，纠正患儿的不良行为。     

抽动障碍共患注意缺陷多动障碍的治疗研究

目的探讨抽动障碍(TD)共患注意缺陷多动障碍(ADHD)应用精神兴奋剂治疗的疗效。方法选择2004年1月至2006年8月在本院多动症专科门诊就诊的确诊为TD共患ADHD患儿69例(DSM-IV诊断标准、Conners量表和YGTSS量表),采用哌甲酯,泰必利或(和)氟哌啶醇联合治疗,随访2月观察疗效和安全性(血压、心律、肝功能等)。结果治疗2个月后Conners量表学习问题、多动指数2个因子,YGTSS量表运动抽动、发声抽动2个因子积分均较治疗前显著减低,差异达到显著统计学意义(P<0.01),结论兴奋剂对抽动症影响不大,小剂量兴奋剂(如哌甲酯)与常规多巴胺受体阻滞剂(泰必利)合用对TD共患ADHD具有较好疗效。     

盐酸哌甲酯缓释制剂治疗注意缺陷多动障碍儿童临床效果的影响因素研究

目的:探讨注意缺陷多动障碍(ADHD)儿童应用盐酸哌甲酯缓释制剂治疗临床效果的影响因素.方法:选取2018年4月—2019年4月于本院就诊的46例ADHD患儿作为研究对象,均给予盐酸哌甲酯缓释制剂治疗.治疗前采用联合型瑞文测验(CRT)评估患儿智力,并根据国际最新方法将ADHD患儿分为注意力缺陷型、冲动型/多动型和混合...     

自我控制训练改善8～12岁ADHD儿童冲动行为的疗效观察

目的 探讨自我控制训练对改善注意缺陷多动障碍(Attention Deficit Hyperactivity Disorder,ADHD)儿童冲动行为的疗效.方法 对32例8-12岁有冲动行为的ADHD儿童进行自我控制训练,在治疗前后采用Barratt冲动性量表中文版(Barratt Impulsiveness Scale,BIS)进行评定,并将两者进行比较.结果 治疗前后ADHD患儿冲动行为明显减少,在BIS中多项指标和总分均有显著性差异(P<0.05).结论 自我控制训练是改善8～12岁ADHD儿童冲动行为的一项有效的治疗手段.     

国内盐酸哌甲酯控释片治疗儿童注意缺陷多动障碍的Meta分析

目的应用Meta分析评价国内盐酸哌甲酯控释片(专注达)与传统药物治疗18岁以下儿童注意缺陷多动障碍(ADHD)的临床疗效。方法通过中国学术期刊网全文数据库(CNKI,1979-2008)、中国生物医学文献数据库(CBMdisc,1978-2008)和国家科技图书文献中心等,检索国内有关盐酸哌甲酯控释片治疗儿童ADHD的随机临床对照试验,由两位评价者进行质量评价,并对符合纳入标准的临床试验研究进行Meta分析。结果共查阅到国内相关临床研究13篇,最终进入评价的临床研究4篇,患儿174例。合并分析表明,盐酸哌甲酯控释片与传统治疗药物比较,可显著降低患儿ADHD-RS量表的评分(P<0.01),平均减分值之差(95%CI)为[-7.85(-9.07,-6.64)]。结论从现有的临床证据看,盐酸哌甲酯控释片在改善18岁以下ADHD患儿的核心症状方面疗效显著。但由于样本数较少,该药与传统治疗药物的疗效对比仍需大规模、高质量、随访结局统一的临床试验进一步验证。     

托莫西汀治疗儿童注意缺陷多动障碍疗效观察

目的:探讨托莫西汀(ATX)对门诊符合DSM-IV诊断标准的注意缺陷多动障碍(ADHD)患儿的有效性及安全性。方法:采用开放性研究方法,对温州市第七人民医院儿童青少年心理门诊诊断为ADHD的患儿共48例口服托莫西汀0.8 mg/(kg·d)治疗8周,采用ADHDRS-IV-Parent:Inv、CGI-ADHD-S、Conners多动指数量表进行临床疗效评定,采用TESS量表对药物不良反应进行临床监测。结果:ADHDRS-IV-Parent:Inv总体有效率77.08%(37/48);治疗前CGI-ADHD-S(5.19±0.71)分、Conners多动总分(26.2±3.1)分、行为总分(39.1±5.2)分,治疗8周后CGI-ADHD-S(2.98±0.89)分、Conners多动总分(12.3±2.9)分、行为总分(18.2±4.6)分,治疗前后比较差异均有统计学意义(P<0.01);其主要的不良反应为食欲下降、上腹痛、恶心呕吐、头晕、心悸等。结论:ATX对ADHD患儿的注意缺陷、多动、冲动症状均有较好的疗效,而且安全性好。     

盐酸哌甲酯缓释片联合感觉统合训练治疗儿童注意缺陷多动障碍的临床观察

目的评价儿童注意缺陷多动障碍行盐酸哌甲酯缓释片、感觉统合训练(SIT)联合治疗的可行性,为儿童注意缺陷多动障碍患儿临床治疗工作提供参考。方法 66例儿童注意缺陷多动障碍患儿,采取随机法分为对照组和试验组,每组33例。对照组口服盐酸哌甲酯控释片治疗,试验组在对照组用药基础上配合感觉统合训练。比较两组患儿治疗前后智力状况评分及治疗后行为状况评分。结果治疗后,两组患儿的全量表智商、言语量表智商及操作量表智商评分均高于本组治疗前,且试验组改善情况优于对照组,差异具有统计学意义(P<0.05)。治疗后,试验组患儿的学习因子、行为因子、心身因子、焦虑因子、冲动因子、多动因子评分分别为(1.55±0.40)、(1.55±0.35)、(0.90±0.23)、(1.45±0.30)、(1.26±0.30)、(1.80±0.35)分,均低于对照组的(1.93±0.43)、(1.78±0.40)、(1.10±0.25)、(1.68±0.33)、(1.82±0.33)、(2.10±0.33)分,差异均具有统计学意义(P<0.05)。结论盐酸哌甲酯缓释片联合感觉统合训练治疗儿童注意缺陷多动障碍在改善患儿的智力状况以及行为状况等方面均有积极意义,建议联合推行应用。     

家庭干预联合托莫西汀对儿童注意缺陷多动障碍的临床观察

目的:探讨家庭干预联合托莫西汀对儿童注意缺陷多动障碍的疗效。方法:选择2018年6月—2019年8月收治的儿童注意缺陷多动障碍患儿50例,在使用托莫西汀的前提下,加以家庭干预。比较治疗前后的Conners评分、儿童行为量表评分。结果:治疗后Conners评分明显比治疗前降低,差异有统计学意义(P<0.05)。治疗后儿童行为量表评分中总分、活动能力、抑郁、攻击、违纪、分裂性、交往不良、强迫性评分明显低于治疗前,社交退缩、学习能力评分明显高于治疗前,差异有统计学意义(P<0.05)。结论:家庭干预联合托莫西汀药物疗法治疗儿童注意缺陷多动障碍,可以有效改善患儿的外化症状,与单纯药物治疗方案对比,可以更有效地改善患儿的注意缺陷症状和多动冲动障碍症状。     

Allosteric interaction of zinc with recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) GABA(A) receptors

In a recent study we have provided evidence that inhibition of native GABA(A) receptors by zinc depends primarily on the allosteric modulation of receptor gating. Both the kinetics and the sensitivity of the GABA(A) receptor to zinc depend on subunit composition, especially on the presence of the gamma(2) subunit. To analyze the mechanism of action of zinc its effects have been tested on recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors expressed in HEK 293 cells. The currents produced by ultrafast application of GABA have been measured to assess the impact of zinc ions on GABA(A) receptor gating with resolution corresponding to the time scale of synaptic currents. While, as expected, zinc markedly reduced the peak amplitude of alpha(1)beta(2)-mediated currents, its effect on kinetics was significantly different from that observed for alpha(1)beta(2)gamma(2). In particular, unlike alpha(1)beta(2)gamma(2), zinc did not affect the onset of alpha(1)beta(2)-mediated responses. Moreover, zinc increased the extent of desensitisation of alpha(1)beta(2)gamma(2) receptors and reduced desensitisation of alpha(1)beta(2) ones. Quantitative analysis suggests that zinc exerts an allosteric modulation on both alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors. Zinc effects on alpha(1)beta(2)gamma(2) were qualitatively similar to those reported for native receptors.     

(S)-(-)-氨磺必利-D-(-)-酒石酸盐的合成

目的研究（S）-（-）-氨磺必利-D-（-）-酒石酸盐的制备方法。方法以4-氨基-2-甲氧基-5-巯基苯甲酸为原料,经乙基化、氧化得4-氨基-2-甲氧基-5-乙基磺酰基苯甲酸（4）,另由1-乙基-2-氨甲基吡咯烷经D-（-）-酒石酸拆分得S-（-）-1-乙基-2-氨甲基吡咯烷（6）,4与6缩合制得S-（-）-氨磺必利（7）,再与D-（-）-酒石酸成盐制得目标物S-（-）-氨磺必利-D-（-）-酒石酸盐（1）。总收率达25%（以4-氨基-2-甲氧基-5-巯基苯甲酸计算）。结果所得产物经元素分析,红外光谱、核磁共振谱及质谱确证了结构。结论本方法原料易得,反应条件温和,产品质量易控制。     

alpha-glucosidase (CHO) (Genzyme)

Genzyme General is developing recombinant human alpha-glucosidase, produced in mammalian cell culture, as a potential treatment for Pompe disease. By July 2004, enrollment was completed in two clinical trials and an observational study in adults. Genzyme was planning to file for regulatory approval in Europe during 2004, followed by filings in the US and Japan in mid-2005.     

Developmental toxicity of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat

Two phthalate esters, di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), have been assessed for their potential to cause developmental toxicity in the rat. Groups of 22 timed-mated Sprague-Dawley rats were administered 250, 500, or 1000 mg/kg D79P or D911P daily by oral gavage (5 ml/kg) between gestation days (GD) 1 and 19. Control animals received the vehicle (olive oil) alone. On GD20, the animals were sacrificed and the fetuses examined. Treatment resulted in no signs of maternal toxicity, as assessed by adjusted maternal bodyweight gain throughout gestation and clinical examinations, and no effects upon litter size, fetal survival or bodyweight. Pups of the high dose D79P and intermediate and high dose D911P groups showed increased incidences of supernumerary lumbar ribs. There was a significant increase in dilated renal pelves in pups of the low dose D79P and high dose D911P groups, but only for D911P was there a significant trend. Consequently, the no observed adverse effect level (NOAEL) for maternal toxicity for both D79P and D911P is 1000 mg/kg/day. The NOAEL values for developmental toxicity are 500 mg/kg/day D79P and 250 mg/kg/day D911P.     

(S)-oxybutynin (Sepracor)

Sepracor is developing (S)-oxybutynin, a single-isomer version of Alza's Ditropan (racemic oxybutynin), a muscarinic acetylcholine receptor antagonist, as a potential treatment for urinary incontinence.     

Psychopharmacological profile of 1-(m-(trifluoromethyl) phenyl) piperazine (TFMPP)

The effect of TFMPP, an agonist of the 5-HT1b receptors, was studied in mice on several psychopharmacological parameters. In contrast to imipramine-like drugs, TFMPP neither antagonized reserpine-induced hypothermia nor increased yohimbine-induced toxicity. Similarly to imipramine-like drugs, TFMPP antagonized oxotremorine-induced hypothermia and was active in the behavioural despair test. In addition, TFMPP normalized a social behavioural deficit induced by isolation. The effects of TFMPP on oxotremorine-induced hypothermia in the behavioural despair test and in the isolation-induced social behavioural deficit are all antagonized by d-1 propranolol. It is concluded that TFMPP seems to possess psychotropic activity resembling only in part that of imipramine-like drugs and that these actions may be mediated through 5-HT1b receptors.     

Two-generation reproduction toxicity studies of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat

Di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), based on high-normality linear oxo-alcohols, have been assessed for their impact upon reproductive performance in Sprague-Dawley rats. Rats were continuously exposed to either D79P or D911P at dietary levels of 0%, 0.1%, 0.5%, or 1.0% over two generations. Selected F(0) offspring (F(1) generation) were exposed to the same dietary concentration of D79P or D911P as the respective F(0) animals, and were mated to produce F(1) offspring. Both D79P and D911P markedly reduced body weight gain in F(0) and F(1) adult males at the highest dose, but females were affected to a lesser extent. There was no impairment of fertility, fecundity, or development in either generation, but body weights of offspring in the 1.0% D79P and 1.0% D911P groups were slightly and transiently reduced over the weaning period. Although decreases in the weight of several organs were accounted for by depressed body weight, ovary weights were reduced in both generations exposed to 1.0% D79P, and epididymidal weights were slightly reduced in adults of both generations exposed to 1.0% D911P. However, ovarian function-assessed by the oestrus cycle and mating behaviour-and epididymidal sperm concentration, motility, and morphology were unaffected by either substance. Treatment resulted in liver changes, particularly in males, characterised by increased liver weight in young animals, histopathologic changes and reduced organ weight in mature animals, and an increase in palmitoyl CoA oxidase activity. In conclusion, neither D79P nor D911P impaired reproductive function in rats when administered in the diet at levels that induce systemic toxicity, and the NOAEL for effects on reproduction in the rat is 0.5% for both D79P and D911P.     

（S）—（＋）—2—氨基丙醇制备新工艺

(S) - ( ) - 2 -氨基丙醇 ( 1 )是合成左氧氟沙星的重要中间体 [1] ,随着左氧氟沙星作为国家基本药物在国内上市 ,开发适合我国国情的制备 1的简便新工艺显得很有必要。文献报道 [2 ,3 ] ,采用 Li Al H4 还原 L-丙氨酸 ( 2 )可以制得 1 ,该法的优点是反应过程简单 ,缺点是Li Al H4 价格昂贵 ,并且比较危险 ,同时后处理也比较复杂。另有文献报道 [4 ] ,先将 2酯化 ,然后采用较为便宜的 KBH4 还原制备 1 ,该法收率太低而不能用于工业化。为了提高收率 ,降低成本 ,我们对后一条合成路线进行了工艺研究 ,在将 2酯化得 L-丙氨酸乙酯 ( 3)…