盖诺加顺铂联合化疗治疗晚期非小细胞肺癌疗效观察

目的：观察国产长春瑞滨（盖诺）加顺铂联合化疗治疗晚期非小细胞肺癌的近期疗效。方法：对50例晚期非小细胞肺癌（NSCLC）采用盖诺加顺铂方案化疗，21天为1周期，治疗2周期以上评定疗效。结果：50例中PR22例，占44．00％；NC21例，占42．00％；PD6例，占12．00％，有效率（CR＋PR）为44．00％，中位生存期8个月。Ⅲ度白细胞下降30％（15/50），Ⅳ度10％（5／50）。结论：盖诺加顺铂是治疗晚期非小细胞癌一个很有价值的方案，不良反应小，患者可以耐受，值得推广。     

两种化疗方案治疗晚期非小细胞肺癌的临床分析

目的观察并探讨顺铂联合长春瑞滨和顺铂联合吉西他滨治疗晚期非小细胞肺癌的疗效及不良反应。方法采用回顾性分析方法,对潮州医院90例非小细胞肺癌患者,铂联合长春瑞滨(NP)方案治疗有45例,顺铂联合吉西他滨(GP)方案治疗有45例,分别比较两组患者的疗效、不良反应发生情况。结果 NP方案有效率为40.00%,GP方案有效率为42.22%,差异无统计学意义(P0.05);两组患者的不良反应主要以血液学毒性,NP治疗方案中Ⅲ~Ⅳ级血小板减少发生率为4.44%、4.44%,NP治疗方案中Ⅲ~Ⅳ级血小板减少发生率为13.33%、8.89%,差异具有统计学意义(P0.05)。结论顺铂联合长春瑞滨(NP方案)和顺铂联合吉西他滨(GP)方案治疗晚期非小细胞肺癌的疗效较好,耐受性好,毒性作者较小,患者可根据自身情况选择合理的方案治疗。     

盖诺联合顺铂治疗初治非小细胞肺癌的疗效观察

目的评价盖诺（长春瑞滨,NVB）联合顺铂（顺氯氨铂,DDP）治疗初治非小细胞肺癌（NSCLC）近期疗效和毒副作用。方法对北京市平谷区医院近4年来84例初治晚期（Ⅲb-Ⅳ）非小细胞肺癌采用盖诺联合顺铂化疗（NP方案）,盖诺25mg/m2·d,d1.8;顺铂25mg/m2·d,d3～5,每3周重复一次,完成3周期或以上评价疗效。结果总有效率34.5%,主要毒副作用是骨髓抑制和消化道反应。结论盖诺联合顺铂治疗晚期非小细胞肺癌疗效确切,毒副反应可耐受,骨髓抑制为其剂量限制性毒性。     

国产长春瑞滨联合顺铂治疗晚期非小细胞肺癌

目的观察国产抗肿瘤药物长春瑞滨(盖诺)和顺铂联合化疗治疗晚期非小细胞肺癌的疗效。方法采用NP方案治疗晚期非小细胞肺癌(NSCLC)38例,男29例,女9例。腺癌28例,鳞癌8例,大细胞癌2例。Ⅲ期20例,Ⅳ期18例；初治25例,复治13例。结果部分缓解(PR)16例,稳定(SD)13例,进展(PD)9例。总有效率为42%。每周盖诺≥25mg/m~2的毒性反应主要是暂时性骨髓抑制,主要表现白细胞数下降86．8%,其中Ⅲ、Ⅳ度为18．4%；局部静脉炎发生率为52．6%。结论国产长春瑞滨(盖诺)替代进口诺维本+顺铂治疗晚期NSCLC可行,其疗效、毒副反应与诺维本相近。     

长春瑞滨联合奥沙利铂治疗晚期非小细胞肺癌疗效观察

目的:探索长春瑞滨(NVB)+奥沙利铂(N0方案)与长春瑞滨+顺铂(NP方案)治疗晚期非小细胞肺癌的疗效.方法:59例非小细胞肺癌患者随机分为治疗组29例和对照组30例.治疗组给予长春瑞滨+奥沙利铂治疗;对照组给予长春瑞滨+顺铂治疗,两组均21天为1个周期,用药2周期.结果:总有效率治疗组为41.1%,对照组为46.7%(P>0.05).不良反应以白细胞减少、恶心、呕吐以及周围神经炎为主.Ⅲ～Ⅳ度的恶心、呕吐,肾功能损害及心功能不全主要发生在对照组,周围神经炎主要发生在治疗组(P<0.05).结论:长春瑞滨+奥沙利铂治疗晚期非小细胞肺癌疗效确切,患者耐受性良好,为晚期非小细胞肺癌的治疗提供了一种新的选择,更适宜老年及心肺功能不全的患者.     

长春瑞滨联合顺铂治疗晚期非小细胞肺癌32例临床分析

目的:观察国产长春瑞滨(盖诺)与顺铂联合化疗治疗晚期非小细胞肺癌的疗效。方法:运用NP方案:长春瑞滨25 mg/m2,第1、8天;顺铂80 m g/m2,分2~4 d静脉滴注。治疗非小细胞肺癌32例。结果:部分缓解(PR)13例,稳定(SD)14例,进展(PD)5例,总有效率40.6%。初治有效率46.4%,复治有效率25%。主要毒副作用为白细胞减少和消化道反应。结论:国产长春瑞滨与顺铂联合化疗治疗晚期非小细胞肺癌是一个疗效好,毒副反应可以接受的一线方案。     

吉西他滨与长春瑞滨治疗晚期非小细胞肺癌的比较研究

目的　比较吉西他滨联合顺铂组成的GP方案与长春瑞滨(去甲长春花碱)联合顺铂组成的NP方案,治疗晚期非小细胞肺癌(NSCLC)的近期疗效和毒性。方法　通过GP和NP两个联合化学治疗方案治疗晚期非小细胞肺癌6 8例。结果　GP组和NP组有效率分别为4 7.2 %和4 3.8% ,两组无显著性差异(P>0.05)。不良反应主要是骨髓抑制。结论　吉西他滨联合顺铂方案与去甲长春花碱联合顺铂方案治疗晚期非小细胞肺癌疗效较高且相似。不良反应可以耐受     

NO NP方案治疗非小细胞肺癌比较

目的评价长春瑞滨联合奥沙利铂和长春瑞滨联合顺铂治疗晚期非小细胞肺癌的近期疗效与不良反应。方法24例非小细胞肺癌患者随机分组采用长春瑞滨联合奥沙利铂(简称NO方案组)和长春瑞滨联合顺铂(简称NP方案组)方案治疗晚期非小细胞肺癌患者,21～28d为一个周期,完成3个周期治疗后评价疗效并观察不良反应。结果NO方案组14例,CR1例,PR5例,有效率为42.9%;NP方案组14例,CR 1例,PR5例,有效率为42.9%(P<0.05)。两组不良反应比较:白细胞减少、血小板减少等不良反应相似;NO组脱发、胃肠道反应较NP组减少(P<0.05),NO方案组周围神经炎发生率高于NP方案组(P<0.05)。结论两方案治疗晚期非小细胞肺癌近期疗效相似;白细胞下降、血小板减少等不良反应相似,而胃肠道反应、脱发等不良反应差别有统计学意义,但均可耐受。     

吉西他滨顺铂治疗晚期非小细胞肺癌

目的观察吉西他滨(GEM)联合顺铂(DDP)(GP方案)对晚期非小细胞肺癌的疗效和毒副作用。方法自2005年12月-2007年8月,对33例晚期非小细胞肺癌采用GP方案治疗。吉西他滨:1000mg/m2,静滴,第1、8d。顺铂:50mg/m2,静滴,第2、3d。21d为1周期,连用2周期。结果33例病例中,无CR病例,其中PR13例,SD14例,PD6例,总有效率CR PR为39.4%(13/33)。中位生存期(MST)为8.7个月。主要的毒副作用为血液学毒性。Ⅲ～Ⅳ度白细胞下降占24.2%(8/33)。结论吉西他滨联合顺铂治疗晚期非小细胞肺癌疗效较高,毒性可耐受。     

吉西他滨联合顺铂治疗老年晚期非小细胞肺癌的疗效观察

目的观察吉西他滨联合顺铂治疗老年非小细胞肺癌的疗效和毒副作用。方法28例老年晚期非小细胞肺癌用吉西他滨联合顺铂方案化疗,每3周重复。结果28例中CR0例,PR11例,NC10例,PD7例,有效率39.3%。结论吉西他滨联合顺铂治疗老年晚期非小细胞肺癌疗效好,不良反应可耐受。     

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.     

(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.     

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.     

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)…