LC-MS/MS法研究左旋去甲基苯环壬酯在比格犬体内的生物利用度

目的评价左旋去甲基苯环壬酯在比格犬体内生物利用度。方法 LC-MS/MS法测定比格犬口服和静脉给药后体内的血药浓度,计算药代动力学参数和绝对生物利用度。结果比格犬口服给药2 mg/kg后5 min即可测得血中药物含量,口服给药后1 h左旋去甲基苯环壬酯在比格犬体内血药浓度达峰,给药后36 h血中药物浓度均已降至LLOQ以下。比格犬口服和静脉注射2 mg/kg左旋去甲基苯环壬酯的t1/2分别为（5.36±0.82）h和（6.73±2.00）h,Cmax分别为（141.88±51.03）和（591.84±144.61）μg/L;AUC（0-36 h）分别为（962.42±220.96）和（1572.06±365.80）μg.L-1.h;用AUC（0-36 h）计算比格犬口服单剂量左旋去甲基苯环壬酯的绝对生物利用度为（61.22±10.78）%。结论左旋去甲基苯环壬酯口服给药吸收迅速,绝对生物利用度较高,具有良好的开发前景。     

姜素预防犬运动病的效果观察

目的　观察姜素预防犬运动病的效果和对豚鼠视前庭相互作用的影响。　方法　采用随机双盲和安慰剂对照实验设计 ,观察 7 2mg/kg ,3 6mg/kg和 1 8mg/kg 3种剂量姜素及苯海拉明 (乘晕宁 3 2mg/kg)、盐酸苯环壬酯 (飞塞乐 0 2mg/kg)对犬运动病预防效果和对豚鼠视前庭系统的影响。犬运动病采用三角离心摆动方式 (峰速 2 4 0°/s ,频率 0 0 5Hz)诱发 ,以一定时间内犬的呕吐发生率作为犬运动病的观察指标 ;以正弦摆动 (峰速 6 0°/s,频率 0 0 5Hz)加光条刺激方式诱发豚鼠视前庭相互作用眼震 ,以眼震次数、慢相速度和增益作为视前庭相互作用观察指标。　结果　 3种剂量姜素均可显著降低犬呕吐发生率 ,且在 7 2mg/kg和 3 6mg/kg剂量时其效果较苯海拉明、盐酸苯环壬酯显著 ,各种药物对豚鼠VVOR眼震均无显著影响。　结论　姜素用于预防对抗运动病效果显著且不会影响正常的视前庭功能     

HPLC法测定左旋盐酸去甲苯环壬酯渗透泵片的含量和有关物质

目的建立高效液相色谱（HPLC）法测定左旋盐酸去甲苯环壬酯渗透泵片的含量和有关物质。方法采用C18色谱柱（250 mm×4.6 mm,5μm）,以乙腈-0.05 mol/L醋酸钠缓冲液（85∶15,pH 6.0）为流动相,检测波长为220 nm,流速为1.0 ml/min,柱温为40℃。结果在优化的色谱条件下,左旋盐酸去甲苯环壬酯与有关物质可有效分离,辅料和溶剂不干扰主药测定;主药的线性范围为30.0～200.0μg/ml（r=0.9998）;平均回收率为99.52%,RSD为0.94%（n=9）。结论该方法简便准确,专属性强,可用于测定左旋盐酸去甲苯环壬酯渗透泵片的含量和有关物质。     

LC-MS/MS法研究左旋去甲基苯环壬酯在比格犬体内的生物利用度

目的评价左旋去甲基苯环壬酯在比格犬体内生物利用度。方法 LC-MS/MS法测定比格犬口服和静脉给药后体内的血药浓度,计算药代动力学参数和绝对生物利用度。结果比格犬口服给药2 mg/kg后5 min即可测得血中药物含量,口服给药后1 h左旋去甲基苯环壬酯在比格犬体内血药浓度达峰,给药后36 h血中药物浓度均已降至LLOQ以下。比格犬口服和静脉注射2 mg/kg左旋去甲基苯环壬酯的t1/2分别为(5.36±0.82)h和(6.73±2.00)h,Cmax分别为(141.88±51.03)和(591.84±144.61)μg/L;AUC(0-36 h)分别为(962.42±220.96)和(1572.06±365.80)μg.L-1.h;用AUC(0-36 h)计算比格犬口服单剂量左旋去甲基苯环壬酯的绝对生物利用度为(61.22±10.78)%。结论左旋去甲基苯环壬酯口服给药吸收迅速,绝对生物利用度较高,具有良好的开发前景。     

右美托咪定对舒芬太尼抑制腹腔镜胆囊术后疼痛半数有效剂量的影响

目的：探究右美托咪定（ Dex）对舒芬太尼抑制腹腔镜胆囊切除术（ LC）后疼痛半数有效剂量（ ED50）的影响。方法选取行LC手术78例患者为研究对象，依据麻醉方法划分为研究组（40例）和参照组（38例），研究组术前给予Dex，参照组不给予Dex，对比两组各个时刻的VAS评分，依据序贯法计算ED50及95％CI。结果各个时刻研究组的评分都明显低于参照组，对比具有显著差异（ P＜0．05）。研究组的40例患者中，镇痛有效例数为20例，镇痛无效例数为20例，根据序贯法计算，ED50为0．563，95％CI为（0．623，0．458） ug／kg。结论术前给予Dex，可明显缓解患者的术后疼痛程度，具有较高临床价值。     

HPLC法测定盐酸左旋去甲基苯环壬酯片的含量及有关物质

目的：建立盐酸左旋去甲基苯环壬酯（ demethyl levophencynonate hydrochloride,L-LPC）片的含量及有关物质的分析方法。方法采用高效液相色谱法;色谱柱Capcel PAK C18柱, MGⅡ5μm,4．6 mm ×250 mm,Col：No．A4AD 02992（Shiseido,日本）;流动相甲醇∶乙腈∶0．05 mol/L醋酸钠缓冲溶液（pH 5．0）为4∶3∶3;流速1．0 ml/min;检测波长220 nm;进样量20μl;柱温为室温。结果方法回收率为（100．15±0．73）％;溶液在8 h保持稳定（RSD为0．36％）;在0．1～50μg/ml范围内线性关系良好,其回归方程为Y＝81558X-4768．3（R2＝1,n＝3）。结论所建立的方法简便、准确、灵敏,专属性强,为该制剂含量测定、半成品测定及制剂稳定性研究提供了方法学依据。     

大鼠血浆中抗抑郁新药阿姆西汀浓度检测方法的建立及其药代动力学

目的：应用液相色谱-串联质谱法（LC-MS/MS）建立大鼠血浆中阿姆西汀（S-071031B）浓度测定方法,并考察大鼠灌胃给予阿姆西汀后的药代动力学。方法采用LC-MS/MS方法,以盐酸苯环壬酯左旋体（ L-8021）为内标,C18柱为分析柱,流动相为含0．1％甲酸的水-乙腈体系,流速为0．3 ml/min,采用电喷雾正离子（ESI ＋）、选择反应监测（SRM）模式进行检测。绘制血药浓度-时间曲线并利用DAS 2．0计算药代动力学参数。结果大鼠血浆中内源性杂质不干扰阿姆西汀和内标的测定,阿姆西汀的线性范围为2～1000 ng/ml （r2＝0．9965）,定量限为2 ng/ml,日内、日间精密度和准确度,绝对回收率和基质效应均符合生物样品测定需要。大鼠口服灌胃后在（0．8±0．3）h达到（287．2±50．8）μg/L的峰值浓度,t1/2为（2．9±0．6）h,AUC（0-∞）为（1372．6±255．3）μg/L· h。结论本方法灵敏度高、特异性好,可用于血浆中阿姆西汀的浓度测定及其药代动力学研究。     

心理应激对大鼠多巴胺受体功能的影响及酪氨酸的干预作用

目的 探讨心理应激对大鼠中枢多巴胺受体功能的影响以及酪氨酸的干预作用。方法 用Communication Box模型对大鼠进行连续14天、每天30min的心理应激，并经饲料给予250、500、1000mg／kg三个剂量的酪氨酸干预。采用放射性配基结合分析法测定不同应激时间的中脑腹侧被盖区（VTA）、伏隔核（Nac）、前额皮质（mPFC）等脑区多巴胺D1、D2受体的最大结合容量（Bmax）和平衡解离常数（Kd）。结果 心理应激组mPFC、Nac区D2受体最大结合容量较对照组有明显下降（P〈O．05），mPFC区D2受体最大结合容量也有明显的下降（P〈O.05）。与心理应激组相比，酪氨酸500mg／kg干预组mPFC区D2受体最大结合容量升高（P〈0．05），1000mg／kg干预组VTA、mPFC区D2受体最大结合容量升高（P〈0．05）。心理应激及酪氨酸干预组D1、D2受体平衡解离常数无明显差别。结论 心理应激能够降低mPFC、Nac区D2受体最大结合容量，酪氨酸干预能够提高心理应激时mPFC、VTA区的D1，受体最大结合容量。心理应激对不同脑区D2受体功能的影响可能不同。     

2—托品醇立体异构体的选择性合成

以２－托品酮外消旋体（１），分别经氧化铂催化氢化和金属钠还原，立体选择性制备２α和２β托品醇，再经左旋和右旋酒石酸拆分，得１Ｒ（５Ｓ），２Ｒ；１Ｓ（５Ｒ），２Ｓ；１Ｓ（５Ｒ），２Ｒ和１Ｒ（５Ｓ），２Ｓ托品醇四个光学异构体。     

依托咪酯对布比卡因致惊厥作用的影响

目的观察依托咪酯（etomidate,Eto）对布比卡因（bupivacaine,Bup）致惊厥作用及半数有效量（ED50）、半数致死量（LD50）的影响。方法皮下注射3种不同剂量的依托咪酯20min后,腹腔注射致惊厥作用的布比卡因,观察小鼠惊厥潜伏期、持续时间、未惊厥数和死亡数;并以序贯法测定预先给予依托咪酯20min后布比卡因的致惊厥ED50和LD50。结果依托咪酯2、4mg/kg可延长布比卡因致小鼠惊厥的潜伏期（P〈0.01）,缩短持续时间（P〈0.01）,减少惊厥发生数和死亡数;增大布比卡因致惊厥的ED50（P〈0.05,P〈0.01）,增大布比卡因的LD50（P〈0.01）。结论依托咪酯能够拮抗布比卡因的致惊厥作用,降低布比卡因的毒性。     

Knee injury and Osteoarthritis Outcome Score (KOOS) - validation of a Swedish version

The Knee injury and Osteoarthritis Outcome Score (KOOS) is a self-administered instrument measuring outcome after knee injury at impairment, disability, and handicap level in five subscales. Reliability, validity, and responsiveness of a Swedish version was assessed in 142 patients who underwent arthroscopy because of injury to the menisci, anterior cruciate ligament, or cartilage of the knee. The clinimetric properties were found to be good and comparable to the American version of the KOOS. Comparison to the Short Form-36 and the Lysholm knee scoring scale revealed expected correlations and construct validity. Item by item, symptoms and functional limitations were compared between diagnostic groups. High responsiveness was found three months after arthroscopic partial meniscectomy for all subscales but Activities of Daily Living.     

Endovascular management of carotid-cavernous fistulas

Objective To investigate endovascular treatment of traumatic direct carotid-cavernous fistulas （CCF） and their complications such as pseudoaneurysms. Methods： Over a five-year period, 22 patients with traumatic direct CCFs were treated endovascularly in our institution. Thirteen patients were treated once with the result of CCF occluded, 8 twice and 1 three times. Treatment modalities included balloon occlusion of the CCF, sacrifice of the ipsilateral internal carotid artery with detachable balloon, coll embolization of the cavernous sinus and secondary pseudoaneurysms, and covered-stem management of the pseudoaneurysms. Results All the direct CCFs were successfully managed endovascularly. Four patients developed a pseudoaneurysm after the occlusion of the CCF with an incidence of pseudoaneurysm formation of 18.2% （4/22）. A total number of 8 patients experienced permanent occlusion of the ICA with a rate of ICA occlusion reaching 36.4% （8/22）. Followed up through telephone consultation from 6 months to 5 years, all did well with no recurrence of CCF symptoms and signs. Conclusion Traumatic direct CCFs can be successfully managed with endovascular means. The pseudoaneurysms secondary to the occlusion of the CCFs can be occluded with stent-assisted coiling and implantation of covered stents.     

The acutely limping child

Acute limping may be the result of multiple pathologies in children. The differential diagnosis varies based on the age of the child. Irrespective of age, the initial imaging work-up includes AP and frog leg radiographs of the pelvis and ultrasound; MRI may sometimes be helpful. In children less than 3 years, infections and trauma are most frequent. MRI is the imaging modality of choice when osteomyelitis is clinically suspected. Between the ages of 3 and 10 years, transient synovitis of the hip and Legg-Calvé-Perthes disease are main considerations but infection, inflammation and focal bony lesions are also considered. In children over 10 years, slipped capital femoral epiphysis also is considered.     

Do Balance Board Training Programs Reduce the Risk of Ankle Sprains in Athletes?

Introduction Ankle sprains are the most common musculo-skeletal injury that occurs in athletes,particularly in sports that require jumping and landing on one foot such as soccer,and basketball(1-4).These injuries often result in significant time loss from participation,long-term disability,and have a major impact on health care costs and resources(5-8).     

High Intensity Interval Training:New Insights

KEY POINTS ·High-intensity interval training(HIT)is characterized by repeated sessions of relatively brief，intermittent exercise.often performed with an“a11 out”effort or at an intensity close to that which elicits peak oxygen uptake(i.e.，≥90%of VO2 peak).     

Developmental validation of the PowerPlex(®) ESI 16 and PowerPlex(®) ESI 17 Systems: STR multiplexes for the new European standard

In response to the ENFSI and EDNAP groups’ call for new STR multiplexes for Europe, Promega^® developed a suite of four new DNA profiling kits. This paper describes the developmental validation study performed on the PowerPlex^® ESI 16 (European Standard Investigator 16) and the PowerPlex^® ESI 17 Systems. The PowerPlex^® ESI 16 System combines the 11 loci compatible with the UK National DNA Database^®, contained within the AmpFlSTR^® SGM Plus^® PCR Amplification Kit, with five additional loci: D2S441, D10S1248, D22S1045, D1S1656 and D12S391. The multiplex was designed to reduce the amplicon size of the loci found in the AmpFlSTR^® SGM Plus^® kit. This design facilitates increased robustness and amplification success for the loci used in the national DNA databases created in many countries, when analyzing degraded DNA samples. The PowerPlex^® ESI 17 System amplifies the same loci as the PowerPlex^® ESI 16 System, but with the addition of a primer pair for the SE33 locus. Tests were designed to address the developmental validation guidelines issued by the Scientific Working Group on DNA Analysis Methods (SWGDAM), and those of the DNA Advisory Board (DAB). Samples processed include DNA mixtures, PCR reactions spiked with inhibitors, a sensitivity series, and 306 United Kingdom donor samples to determine concordance with data generated with the AmpFlSTR^® SGM Plus^® kit. Allele frequencies from 242 white Caucasian samples collected in the United Kingdom are also presented. The PowerPlex^® ESI 16 and ESI 17 Systems are robust and sensitive tools, suitable for the analysis of forensic DNA samples. Full profiles were routinely observed with 62.5 pg of a fully heterozygous single source DNA template. This high level of sensitivity was found to impact on mixture analyses, where 54–86% of unique minor contributor alleles were routinely observed in a 1:19 mixture ratio. Improved sensitivity combined with the robustness afforded by smaller amplicons has substantially improved the quantity of data obtained from degraded samples, and the improved chemistry confers exceptional tolerance to high levels of laboratory prepared inhibitors.