光动力药物血卟啉单甲醚HPLC-荧光检测法的建立及其药代动力学研究

目的建立测定血浆中血卟啉单甲醚(HMME)的HPLC-荧光检测法,并用以进行HMME在犬体内的药代动力学研究。方法血浆中的HMME采用乙酸乙酯液-液萃取,荧光素为内标。选用C18柱(4·6mm×150mm,5μm),0·02mol/L醋酸钠(用冰醋酸调pH6·0)-四氢呋喃(60∶40)组成为流动相,荧光检测器激发波长为395nm,发射波长为613nm。结果HMME血药浓度的范围为0·025~5·000μg/mL,采用两条标准曲线定量的方法,两条标准曲线的线性范围分别为:0·025~0·500μg/ml(r=0·9973)和0·25~5·00μg/ml(r=0·9999),提取回收率92·1%~99·2%,日内、日间RSD分别为3·3%~8·4%和3·8%~8·5%。静脉给药后,HMME在犬体内的药代动力学符合开放二房室模型。其主要药代动力学参数:T1/2α(分布半衰期)=(0·18±0·16)h,T1/2β(消除半衰期)=(14·24±3·41)h,Vd(中央室表观分布容积)=(6·37±3·70)L/g,CL(清除率)=(0·31±0·17)L·kg-1·L-1,AUC(0-tn)(血药浓度-时间曲线下面积)=(27·40±11·72)mg·h-1L·-1。结论HPLC-荧光检测法准确、灵敏,适用于HMME药代动力学研究。HMME在犬体内的药代动力学过程符合开放二室模型,其在犬体内可以迅速消除,可很好地消除光动力学疗法的主要副作用———正常组织的持久光毒反应。     

国产复方氨酚氢可酮片人体生物等效性研究

目的:评价国产与进口复方氨酚氢可酮片的生物等效性.方法:20名健康男性志愿者随机交叉单剂量口服国产或进口复方氨酚氢可酮片2片,采用高效液相色谱-紫外法和高效液相-质谱-质谱法分别测定血浆中对乙酰氨基酚和重酒石酸氢可酮的浓度.结果:国产与进口复方氨酚氢可酮片剂中对乙酰氨基酚的Cmax分别为(15.18±4.14)和(15.35±5.24)mg/L,Tmax分别为(0.56±0.35)和(0.57±0.41)h,t1/2分别为(2.21±0.56)和(2.32±0.82)h;AUC0-tn分别为(37.07±7.44)和(36.55±9.38)mg·L-1·h,AUC0-∞分别为(39.51±7.58)和(39.59±9.73)mg·L-1·h,国产制剂的相对生物利用度为(107.72±34.94)%.国产与进口复方氨酚氢可酮片剂中重酒石酸氢可酮的Cmax分别为(30.24±7.11)和(27.89±6.26)μg/L,Tmax分别为(0.90±0.40)和(1.03±0.56)h,t1/2分别为(6.05±0.75)和(6.35±1.19)h,AUC0-tn分别为(189.39±40.39)和(183.19±48.74)μg·L-1·h,AUC0-∞分别为(201.81±44.88)和(197.43±53.83)μg·L-1·h,国产制剂的相对生物利用度为(105.74±17.27)%.结论:国产复方氨酚氢可酮片与进口复方氨酚氢可酮片具有生物等效性.     

克林霉素磷酸酯分散片人体生物等效性研究

目的评价克林霉素磷酸酯分散片在健康人体相对生物利用度及生物等效性。方法受试者随机、自身双交叉、单剂量口服受试制剂或参比制剂300 mg,采用液相色谱串联质谱法测定血浆中药物浓度,药动学参数采用DAS软件处理获得。结果两种制剂Cmax分别为（2.896±1.007）、（3.009±0.755）μg/ml,Tmax分别为（2.11±0.96）、（1.89±0.92）h,t1/2分别为（1.94±0.39）、（1.86±0.30）h,AUC0-tn分别为（12.625±4.956）、（11.658±3.829）μg.h/ml,AUC0-∞分别为（13.027±5.323）、（11.948±4.057）μg.h/ml;相对于参比制剂,受试制剂的生物利用度F0-tn为（107.8±17.4）%。受试制剂和参比制剂的Cmax、AUC0-tn和AUC0-∞经对数转换后进行方差分析,两制剂间无显著性差异。结论重庆巨琪诺美制药有限公司研制的克林霉素磷酸酯分散片与大同云华药业有限公司生产的克林霉素磷酸酯片具有生物等效性。     

HPLC测定小儿棕色口服溶液中愈创木酚甘油醚的含量

目的建立小儿棕色口服溶液中的愈创木酚甘油醚的含量测定方法。方法愈创木酚甘油醚的含量测定：采用HPLC法,色谱柱为Inertsil ODS-3柱（4．6mm×150mm,5μm）;以甲醇-0．05mol·L^-1柠檬酸溶液（35：65,V／V）为流动相,检测波长273nm。流速：1．0mL／min;柱温：30％;进样量5μL。结果愈创木酚甘油醚在5．76～13．44μg·mL^-1的范围内线性关系良好（r=0．9999）,样品的平均回收率为98．89％,RSD为0．61％。结论本文的含量测定方法操作简便快速,结果准确可靠,可用于小儿棕色口服溶液的质量标准。     

固相萃取RP-HPLC法测定西达本胺血药浓度

目的建立测定西达本胺血药浓度的固相萃取RP-HPLC法。方法采用KromasilKR100-5C18(4.6mm×250mm,5μm)分析柱:柱温为室温;以0.6%醋酸水溶液-乙腈(0~6min,81∶19和6~13min,76∶24,v/v)为流动相,梯度洗脱;流速为1.0ml/min;紫外检测波长为260nm;以MS-275为内标,血浆样品用WatersOASIS固相萃取(SPE)小柱提取纯化,乙腈洗脱,吹干,用流动相复溶后进样分析,进样量20μl。结果西达本胺血药浓度在0.04~10μg·ml-1范围内线性关系良好(r=0.9981),最低定量浓度为0.04μg·ml-1。低、中、高3个浓度的日内RSD为5.79%~10.16%,日间RSD为2.01%~14.81%;RE为-0.85%~4.39%;平均回收率为74%。结论此方法较简便、准确、精密度好,可以用做西达本胺的毒代动力学研究,并为临床前药代动力学研究打下了方法学基础。     

冠舒滴丸中葛根素的含量测定

目的建立HPLC法测定冠舒滴丸中葛根素的含量。方法色谱柱:SHIMADZU VP-ODS柱(250 mm×4.6 mm,5μm);流动相:水-甲醇-乙腈(80∶10∶10);流速:1.0 ml/min;检测波长:250 nm;柱温:30℃;进样量:20μl。结果葛根素在12.8～102.4μg/ml范围内呈良好线性关系,回归方程为Y=8 644 510.417X-876 895.15,r=0.9998,平均回收率为99.54%,RSD为0.15%。结论方法操作简便、可靠,灵敏度高,重复性好,可用于该制剂的质量控制。     

注射用清开灵中栀子苷在家兔体内的药动学研究

目的建立高效液相色谱法测定血浆中注射用清开灵主要成分栀子苷的方法 ,研究其在家兔体内的药代动力学,为临床用药提供新的药代动力学参数。方法采用GeminiC18色谱柱（250mm×4.6mm,5μm）,流动相：乙腈-水（14∶86）,紫外检测波长：238nm,流速：1ml/min,进样量：20μl,柱温：40℃。3只家兔静脉滴注注射用清开灵后,采集不同时间点的血药浓度,计算其药动学参数。结果在选定的色谱条件下,注射用清开灵中栀子苷与血浆中其他成分分离良好。栀子苷的血药浓度范围：0.11～7.32μg/ml（r=0.9979）。栀子苷高、中、低3种浓度方法回收率大于96.3%、萃取回收率大于94.0%;日内和日间精密度RSD分别小于4.9%、3.2%,最低检测限为0.11μg/ml。将血药浓度数据采用3P97软件拟合,结果符合一室模型。栀子苷的主要药动学参数：t1/2为（0.33±0.03）h,V为（0.71±0.10）L,CL为（1.47±0.07）L/h,AUC0→4.5h为（3.71±0.20）μg.h/ml。AUC0→∞（4.22±0.37）μg.h/ml。结论本文方法简便、准确,其药代动力学数据为临床注射用清开灵中栀子苷血药浓度的监测和药代动力学研究提供了依据。     

HPLC法测定人血浆中克林霉素含量及其药动学研究

目的建立人血浆中克林霉素的HPLC检测方法。方法采用HPLC法检测人血浆中克林霉素含量,检测条件为:色谱柱:InertsilDOS-3 C185μm硅胶柱(250 mm×4.6 mm);流动相:乙腈/0.05 M KH2PO4=30/70(v/v),流速:1 ml/min;柱温:35℃,检测波长:204 nm,进样量为100μl。结果血浆中克林霉素浓度在0.20~16.0μg/ml范围内线性关系良好(r=0.9992~0.9998),最低检测浓度为0.20μg/ml,方法学回收率为82.42%~89.37%,日内及日间精密度RSD<15%。结论此方法专属、准确、灵敏度高,样品处理过程简便,适合克林霉素临床药代动力学研究。     

HPLC法测定地氯雷他定片的含量

目的采用HPLC法测定地氯雷他定片含量。方法 Agilent Eclipse XDB-C18色谱柱(4.6 mm×150 mm,5μm),以甲醇-10 mmol/L磷酸二氢钾(50∶50)为流动相,流速:1.0 ml/min,检测波长:241 nm,进样量:20μl。结果地氯雷他定在12.5～125μg/ml范围内线性关系良好(r=0.9999),平均回收率为98.7%。结论本方法精密度好,结果准确、可靠、灵敏,可用于地氯雷他定片的含量测定。     

头孢拉定胶囊人体药代动力学和生物等效性

目的研究头孢拉定胶囊在健康人体内的相对生物利用度和生物等效性,为新药报批及其临床应用提供依据。方法20名健康受试者随机双交叉试验方法,单剂量口服受试及参比制剂500 mg,用HPLC法测定给药后不同时间的血药浓度,计算主要药代动力学参数。结果口服头孢拉定胶囊受试制剂和参比制剂后的主要药动学参数:T1/2分别为0.841±0.165和0.842±0.213 h;Cm ax分别为(15.922±2.584)和(15.922±2.584)mg/L;Tm ax分别为(1.225±0.197)和(1.225±0.242)h;AUC0-t分别为(25.399±5.806)和(26.159±5.989)mg/(L.h)。以AUC0-t计算,与参比制剂相比受试制剂中头孢拉定的平均相对生物利用度为(97.4±7.0)%。结论两制剂生物等效。     

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.     

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).     

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.     

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.     

Bronchial stump fistula :treatment with covered retrievable hinged metallic stents-preliminary clinical experience

Objective To evaluate the preliminaily clinical efficacy and retrievability of a retrievable hinged covered metallic stent in the treatment of the bronchial stump fistula （BSF）. Methods Between April 2003 and March 2005, 8 patients with bronchial stump fistula after pneumonectomy or lobectomy were treated with two types （A and B） of retrievable hinged covered metallic stents. Type A stent was placed in 6 patients and type B in 2 under fluoroscopic guidance. The stent was removed with a retrieval set when BSF was healed or complications occurred. Results Stent placement in the bronchial tree was technically successful in all patients, without procedure-related complications. Immediate closure of the BSF was achieved in all patients after the procedure. Stents were removed from all patients but one. Removal of the stents was difficult in two patients due to tissue hyperplasia. Patients were followed up for 6 - 21 months. Placement of the stents remained stable in all patients except one due to severe cough. Permanent closure of BSF was achieved in 7 （87.5%） of 8 patients. Conclusion Use of a retrievable hinged covered expandable metallic stent is a simple, safe, and effective procedure for closure of the BSF. Retrieval of the stent seems to be feasible. （J Intervent Radiol, 2007, 16： 253-257）     

Prevalence and severity of hip and groin pain in sub‐elite male football: a cross‐sectional cohort study of 695 players

The purpose of this study was twofold: (a) to investigate the prevalence of hip and groin pain in sub‐elite male adult football in Denmark and (b) to explore the association between prevalence and duration of hip and groin pain in the previous season with the Copenhagen Hip and Groin Outcome Score (HAGOS) in the beginning of the new season. In total 695 respondents from 40 teams (Division 1–4) were included. Players completed in the beginning of the new season (July–Sept 2011) a self‐reported paper questionnaire on hip and/or groin pain during the previous season and HAGOS. In total 49% (95% CI: 45–52%) reported hip and/or groin pain during the previous season. Of these, 31% (95% CI: 26–36%) reported pain for >6 weeks. Players with the longest duration of pain during the previous season had the lowest HAGOS scores, when assessed at the beginning of the new season, P < 0.001. This study documents that half of sub‐elite male adult football players report pain in the hip and/or groin during a football season. The football players with the longest duration of pain in previous season displayed the lowest HAGOS scores in the beginning of the new season.