12例COPD患者奈替米星药动学及其下呼吸道浓度测定

目的:探讨COPD老年患者奈替米星的药代动力学特性及其下呼吸道浓度分布.方法:一天一次静脉滴注奈替米星7mg/kg,以尿素作为肺泡液稀释内标,用荧光偏振免疫法测定血清、支气管分泌液和肺泡液中奈替米星浓度.结果:奈替米星7mg/kg一天一次静脉滴注30min,血清峰浓度26.71±4.95mg/L,消除半衰期3.69h;肺泡液中药物峰浓度7.76±2.13mg/L ,相当于血清峰浓度的29%,两者具有显著相关性(r=0.986),且超过常见肺炎致病菌的MIC 值;支气管分泌液药物浓度与血清峰浓度无相关性(r=0.687).结论:奈替米星一天一次静脉滴注7mg/kg用于COPD老年患者能有效治疗肺部感染.     

新生儿奈替米星的药物动力学

目的:探讨新生儿奈替米星(Net)的药物动力学.方法:用荧光偏振免疫分析法测定9例新生儿肺炎患者首次单剂量iv 2.5mg/kg Net的血药浓度.结果;Net在新生儿的体内过程符合二室开放模型,主要药物动力学参数为:T_1/2(?)=(14. 88士4. 94)min,T_1/2β=(2.53土0。24)h,Vc=(0.39土0.14)L/kg,CL=(0.15士0.07)L/h.结论:新生儿Net药物动力学与国内成人(P<0.01)、国外成人(P<0.01)、新生儿、儿童均有明显差异;建议新生儿Net给药方案为 2.5mg/kg iv,bid.     

12例COPD患者奈替米星药动学及其下呼吸道浓度测定

目的:探讨COPD老年患者奈替米星的药代动力学特性及其下呼吸道浓度分布.方法:一天一次静脉滴注奈替米星7mg/kg,以尿素作为肺泡液稀释内标,用荧光偏振免疫法测定血清、支气管分泌液和肺泡液中奈替米星浓度.结果:奈替米星7mg/kg一天一次静脉滴注30min,血清峰浓度26.71±4.95mg/L,消除半衰期3.69h;肺泡液中药物峰浓度7.76±2.13mg/L ,相当于血清峰浓度的29%,两者具有显著相关性(r=0.986),且超过常见肺炎致病菌的MIC 值;支气管分泌液药物浓度与血清峰浓度无相关性(r=0.687).结论:奈替米星一天一次静脉滴注7mg/kg用于COPD老年患者能有效治疗肺部感染.     

奈替米星注射液引起休克1例

患者,女,51岁,2005年1月12日,患者因结石性胆囊炎来我院普外科住院。医嘱:奈替米星注射液(江苏济川制药有限公司,批号040325,规格:0.1g)0.2g 0.9%氯化钠注射液250mL,gtt,iv,qd;左氧氟沙星注射液0.2g,gtt,iv,bid。当日上午11:20,输注奈替米星注射液时,患者自诉口唇轻微麻木,余未     

尼卡地平注射剂治疗重度高血压的临床疗效

目的:观察尼卡地平iv gtt治疗重度高血压的降压疗效及安全性.方法:多中心入选54例原发性重度高血压并接受尼卡地平治疗12h.观察临床症状、不良反应、BP和HR变化.结果:总有效率100%,用药后5min血压即明显下降,30min达显效水平,1.5h达最大降压效应并平稳维持至用药结束;达目标血压的药物滴速、累积量、时间分别为(55±28)μg/min、(2.10±1.52)mg、(38±19)min.维持目标血压的药物滴速为(49±25)μg/min,12h总量为(35.5±10.2)mg;不良反应发生率为 9.3%.结论:尼卡地平iv gtt能快速、有效地控制重度高血压的血压水平.     

静滴硫酸奈替米星致药疹1例

【病例】女，50 a。因乳腺癌在我院施乳腺癌根治术。术后给予NS 250mL＋硫酸奈替米星注射液（福建省福清药业有限公司，批号040802，每支50mg）0．1g，iv gtt，bid，静滴d5出现全身弥散性红斑丘疹，以腰骶部、胸腹部为甚，丘疹大部融合为小片状红斑，瘙痒。患者既往无药物过敏史，未进食可引起过敏的食物。本次为首次应用奈替米星，考虑为奈替米星引起的迟发性过敏反应。即停用奈替米星，给予NS 10mL，地塞米松10mg，iv，二盐酸西替利嗪（商品名：仙特敏，比利时联合化工企业集团医药部，批号2002-10）5mg,po,qd，1 d后症状逐渐缓解。     

奈替米星注射液治疗新生儿感染性疾病的临床观察

目的了解奈替米星应用于新生儿感染性疾病的疗效及不良反应.方法42例患感染性疾病的足月新生儿,应用奈替米星7 mg/(kg@d)连用7 d为一疗程,并同时观察用药前后症状、体征、血常规、ALT、BUN、SCr及尿常规等变化.结果本组治疗总有效率100%,治疗7 d痊愈24例(57.14%),好转18例(42.86%),无病情恶化病例,ALT、BUN、SCr结果示治疗前后无明显差异,仅个别病人用药7 d后出现微量尿蛋白6例(14.28%)及红细胞3例(7.14%).结论奈替米星治疗新生儿常见感染性疾病效果好,过敏反应少,肾毒性低,但对个别病人仍应注意尿常规变化,药物应用时间不宜过长.     

慢性阻塞性肺疾病老年患者奈替米星qd给药的药物动力学和临床疗效

目的对慢性阻塞性肺部疾病(COPD)院内感染老年患者qdivgtt奈替米星(NTM)的药物动力学及其在下呼吸道的分布进行研究,并观察临床疗效和不良反应.方法以尿素作为肺泡液稀释内标,用荧光偏振免疫法测定血清、支气管分泌液和肺泡液中NTM浓度.结果NTM7mg/kgqdivgtt(30min),血清cmax(26.71士4.95)mg/L,消除半衰期3.96h;肺泡液中cmax(7.76土2.13)mg/L,相当于血清cmax的29%.支气管分泌液药物浓度与血药浓度无相关性.qd给药使肺泡中药物浓度超过常见肺炎致病菌的MIC值.连续用药7d,31例患者未见肝、肾、神经毒性.结论NTMqdivgtt,由于给药间隔长,可适用于COP)院内感染老年患者.     

卡铂对肿瘤患者的药物动力学与药效学

目的:研究国产卡铂(CBP)的临床药物动力学与药效学,方法:12例肿瘤病人iv gtt CBP 400mg,用反相HPLC法测定血清CBP浓度,并按残数法拟合药物动力学模型和参数.结果:12例肿瘤病人iv gtt CBP结束时的平均血药浓度(?).为55.10±13.00)mg/L,消除半衰期(T._(2?))为(143.09±49.36)min,清除率(CL)为(45.17±16.68)ml min.有效组和无效组的(?)分别为(61.03±9.28)和(52.14±12.77)mg/L,T_(?)分别为(191.27±26.92)和(119.00±35.31)min(P<0.01),CL分别为(31.42±6.79)和(52.04±15.97)ml/min(P<0.05).在2～10h内.有效组血清CBP浓度高于无效组(P<0.05).结论:肿瘤病人iv gtt CBP的血药浓度存在明显个体差异,且疗效与血药浓度和清除快慢有关.     

国产硫酸奈替米星注射剂疗效与安全性评价

目的 评价国产硫酸奈替米星注射剂的疗效与安全性. 方法 采用自制调查表对应用过国产硫酸奈替米星注射剂的住院患者疗效和安全性进行回顾性调查和统计分析. 结果 使用过国产硫酸奈替米星注射剂及联合其他抗菌药物治疗感染的病例71例,其中15例单独使用. 均采用静脉滴注的给药方式. 用药剂量为0.1～0.4 g,qd或bid, 溶媒量100～250 mL,平均用药天数（8.09 ±4.95） d. 治疗感染总有效率81.4%. 不良反应发生率11.3%（8/71）,主要为皮疹、腹泻、血尿素氮升高、转氨酶升高等. 结论 国产硫酸奈替米星治疗感染有效,只要严格按适应证合理使用,不良反应较少,较轻,易于处理. 老年患者应用时需按轻度肾功能减退患者的用法用量减量用药,有变态反应史和年龄偏高患者应慎用.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Comparison of formation of thiolactones and active metabolites of prasugrel and clopidogrel in rats and dogs

1. Prasugrel and clopidogrel are antiplatelet prodrugs that are converted to their respective active metabolites through thiolactone intermediates. Prasugrel is rapidly hydrolysed by esterases to its thiolactone intermediate, while clopidogrel is oxidized by cytochrome P450 (CYP) isoforms to its thiolactone. The conversion of both thiolactones to the active metabolites is CYP mediated. This study compared the efficiency, in vivo, of the formation of prasugrel and clopidogrel thiolactones and their active metabolites.

2. The areas under the plasma concentration versus time curve (AUC) of the thiolactone intermediates in the portal vein plasma after an oral dose of prasugrel (1 mg kg^?1) and clopidogrel (0.77 mg kg^?1) were 15.8 ± 15.9 ng h ml^?1 and 0.113 ± 0.226 ng h ml^?1, respectively, in rats, and 454 ± 104 ng h ml^?1 and 23.3 ± 4.3 ng h ml^?1, respectively, in dogs, indicating efficient hydrolysis of prasugrel and little metabolism of clopidogrel to their thiolactones in the intestine.

3. The relative bioavailability of the active metabolites of prasugrel and clopidogrel calculated by the ratio of active metabolite AUC (prodrug oral administration/active metabolite intravenous administration) were 25% and 7%, respectively, in rats, and 25% and 10%, respectively, in dogs.

4. Single intraduodenal administration of prasugrel showed complete conversion of prasugrel, resulting in high concentrations of the thiolactone and active metabolite of prasugrel in rat portal vein plasma, which demonstrates that these products are generated in the intestine during the absorption process.

5. In conclusion, the extent of in vivo formation of the thiolactone and the active metabolite of prasugrel was greater than for clopidogrel’s thiolactone and active metabolite.

     

PTEN和DNA含量与非小细胞肺癌侵袭转移的关系探讨

目的 研究非小细胞肺癌(NSCLC)组织中抑癌基因PTEN的表达和DNA含量与NSCLC侵袭、转移的关系.方法 采用免疫组织化学SP方法检测PTEN在78例肺癌标本中的表达,并用流式细胞术检测30例肺癌标本中DNA含量.结果:肺癌标本中PTEN蛋白总缺失率为42.3%,有淋巴结转移组和无淋巴结转移组肺癌表达缺失率分别为52.1%和26.7%(P＜0.05),其表达缺失率随TNM分期增加而上升,分期越晚表达缺失率越高.PTEN缺失率高者生存时间短.DNA指数(DI)的分布范围在1.04～1.93.异倍体肿瘤24例,DI值随TNM分期增加而增加(P＜0.05),与淋巴结转移呈正相关.结论 肺癌组织中PTEN的表达与肺癌淋巴结转移有显著相关性,肺癌细胞DNA含量与肺癌TNM分期及淋巴结转移密切相关.检测PTEN蛋白表达和DNA含量将有助于判断肺癌的转移及预后.     

阿立哌唑与利培酮治疗自闭症谱系障碍与注意缺陷多动障碍共病患儿的疗效与安全性评价

目的：评价阿立哌唑与利培酮治疗自闭症谱系障碍（ASD）与注意缺陷多动障碍（ADHD）共病患儿的疗效与安全性。方法：选取在某院精神科治疗的ASD和ADHD共病患儿68例,根据随机数字表法将患儿分为阿立哌唑组（n=34）和利培酮组（n=34）。阿立哌唑组患儿接受起始剂量为5 mg·d^-1的阿立哌唑片口服治疗,最终剂量增加至15 mg·d^-1。利培酮组患儿接受起始剂量为1 mg·d^-1的利培酮片口服治疗,最终剂量增加至2 mg·d^-1;2组患儿均治疗12周。在基线（T₀）、治疗6周（T₁）与12周（T₂）时,采用注意缺陷/多动评定量表（ADHD-RS）评价患儿总体ADHD症状变化情况;采用康纳斯行为评定量表（CRSR）教师用量表多动因子（CRSR-I）评价患儿多动症的改善情况;采用CRSR不注意缺陷-冲动因子（CRSR-H）评价患儿注意力缺陷的改善情况;采用临床整体印象-严重程度量表（CGI-S）及儿童总体评估量表（C-GAS）评分评价患儿整体功能。对患儿的相关临床指标进行常规监测,比较2组患儿药物不良事件与安全性。结果：与T₀时比较,阿立哌唑组患儿T₁与T₂时,ADHD-RS、CRSR-I、CRSR-H与CGI-S评分均显著降低（均P<0.05）,C-GAS评分显著提高（P<0.05）。利培酮组患儿T₂时,ADHD-RS、CRSR-I、CRSR-H与CGI-S评分均显著降低（均P<0.05）,C-GAS评分显著提高（P<0.05）。2组患儿的ADHD症状显著改善,多动症状与不注意缺陷-冲动症状显著改善,患儿的整体功能也显著改善。2组患儿主要的不良事件是食欲增加、体质量增加与嗜睡,但均没有发生严重的不良事件。T₂时,利培酮组患儿催乳素水平显著提高（t=9.619,P<0.001）,其他临床指标没有显著性差异（均P>0.05）。结论：阿立哌唑和利培酮能够通过减少ASD和ADHD共病患儿的注意力涣散和多动症症状来改善患儿整体功能,具有较高的疗效、安全性,值得临床推广应用。     

Whole-body retention of mercury and selenium and histopathological and morphological studies of kidneys and liver of rats exposed repeatedly to mercuric chloride and sodium selenite

Distribution and retention of mercury and selenium was studied in rats exposed repeatedly to HgCl₂ injections (0.5 mg Hg/kg to the tail vein every other day) and intragastrically to Na₂SeO₃ (0.5 mg Se/kg every day), applying combined and separate administration of these metals for 2 weeks. Whole-body retention of mercury in the presence of selenium was augmented by 20% and that of selenium in the presence of mercury by 4% with respect to the administered dose. Combined administration of mercuric chloride and sodium selenite brought about damage to the epithelial cells of renal proximal convolutions and formation of protein casts in their lumen. These changes had the same pattern as those induced by administration of mercuric chloride alone, but the intensity was lower. Submicroscopic studies revealed that repeated combined administration of sodium selenite and mercuric chloride did not completely abolish the mercury-induced mitochondrial swelling and contributed to chromatin destruction in the hepatocyte nuclei.This work was supported by the Section of Medical Sciences of the Polish Academy of Sciences (Agreement 537/VI)     

阿立哌唑与利培酮治疗痴呆精神行为症状的疗效及安全性比较

目的观察阿立哌唑和利培酮治疗老年痴呆精神行为症状的疗效及安全性。方法采用随机对照研究,将具有精神行为症状的痴呆患者68例完全随机分为阿立哌唑组及利培酮组,各34例。阿立哌唑组患者服用阿立哌唑,起始剂量2．5mg／d,最大剂量不超过15mg／d;利培酮组患者口服利培酮,起始剂量0．5mg／d,最大剂量不超过3mg／d。疗程均为8周。治疗前和治疗第2、4、8周末采用痴呆病理分析评定量表（BEHAVE—AD）评定疗效,用副反应量表（TESS）评定不良反应,并于入组时和治疗第8周末分别检测2组患者空腹血糖、餐后2h血糖、TC、TG、LDL—C、HDL—C及体重。结果阿立哌唑组和利培酮组患者治疗2、4、8周后BEHAVE—AD评分均明显低于治疗前[阿立哌唑组：（14．8±4．2）、（10．2±3．6）、（6．8±2．8）分比（16．4±4．6）分;利培酮组：（15．2±3．9）、（11．8±3．8）、（7．2±3．0）分比（17．2±5．O）分,P〈0．05或P〈0．01]。2组患者间治疗前及治疗后BEHAVE—AD评分比较,差异均无统计学意义（P〉0．05）。2组不良反应发生率均为8．8％（3／34）,差异无统计学意义（P〉0．05）。利培酮组治疗8周末体重较治疗前增加明显[（71±6）kg比（66±6）kg,P〈0．05],TG及LDL—C升高[分别为（1．62±0．46）mmol／L比（0．96±0．29）mmol／L．（3．82±0．86）mmol／L比（3．08±0．74）mmol／L,而阿立哌唑组则改变不明显（均P〉0．05）。结论阿立哌唑治疗老年痴呆精神行为症状总体疗效、安全性与利培酮相当,但阿立哌唑对患者血糖、血脂及体重影响小于利培酮。     

Correlation of behavioral and neurochemical effects of d- and l-amphetamines

In an attempt to correlate the behavioral and neurochemical effects of d- and l-amphetamines, the time courses of the effects of the two isomers (1 mg/kg; base, i.p.) were studied on spontaneous motor activity (SMA) and stereotyped behavior (ST) as well as on the concentrations of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in discrete brain areas, such as the caudate nucleus (CN), pons-medulla (PM), and diencephalonmidbrain (DM) in rats. In addition, the dose-response relationship for d-isomer (0.5–2 mg/kg, i.p.) and l-isomer (1–4 mg/kg, i.p.) was also studied on SMA and ST. SMA increased with the dose up to 1.5 mg/kg for d-isomer and up to 3 mg/kg for l-isomer and then decreased, whereas ST increased with the dose for both the isomers. At 1 mg/kg dose, SMA reached its peak during the fourth postdrug 20–minute period for both d- and l-isomers, whereas ST reached its peak during third to fifth 20-minute periods for d-isomer and during the third period for the l-isomer. The d-isomer significantly increased the DA levels in the CN and DM at 30 minutes postdrug, which reached their maximum at 60 minutes, whereas NE levels in the PM had no significant change at 30 minutes, but were significantly reduced in the DM at 30 minutes and in both PM and DM at 60 minutes postdrug; 5-HT levels in the PM and DM showed no significant change. Compared to d-amphetamine, the l-isomer at 30 and 60 minutes postdrug caused more or less similar changes in the NE levels in the DM and PM, whereas it produced less increase in the DA levels in the CN and DM and significant decrease in 5-HT levels in the DM and PM. It appears that the difference in the behavioral effects induced by the two isomers of amphetamine may be due to the difference in their effects on dopaminergic and serotonergic systems.