对破伤风抗毒素试验制剂的配制及结果观察的探讨

破伤风抗毒素(简称TAT)是外伤患者最常用的预防性用药。由于TAT是一种异性蛋白质,注射时易引起某些个体发生过敏反应。故在注射前均需做过敏试验,在已往的临床试验中,阳性率较高。近一年来笔者应用新的方法,对门诊就诊的160名伤患者采取分组的方法进行试验,并加以比较,现将试验方法及结果报告如下,供临床同行们参考。

BASIC语言求算药物制剂稳定性试验参数的程序

应用BASIC语言在QBASIC环境下求算药物制剂稳定性试验参数,即标示量95%单侧可信限的置信区间及药品的有效期。该方法简明扼要,且克服了手工计算步骤烦琐、易出差错的缺点。

HPLC-MS测定人血浆中非那雄胺及相对生物利用度

目的:建立正常人血浆中非那雄胺的 HPLC-MS 测定法,研究2种非那雄胺片在正常人的相对生物利用度。方法:以普罗帕酮为内标,血浆样品沉淀蛋白后,经 Nucleodur C_(18)柱分离后采用质谱检测器检测,20名健康志愿者采用自身对照随机交叉试验设计,分别单剂量口服非那雄胺片5mg 后测定两者相对生物利用度。结果:非那雄胺与内标分离度好,内源性杂质不干扰测定,回归方程为 Y=5.930×10^(-3)X+2.363×10^(-3),r=0.9998。在1.53～306.7ng·mL^(-1)。范围内非那雄胺浓度与峰面积比的线性关系良好,定量限为1.53ng·mL^(-1),回收率为95.8%～103.6%(n=5),日内 RSD 为2.2%～4.7%(n=5);日间 RSD 为2.2%～3.6%(n=5)。单次服用5mg 非那雄胺片试验制剂或参比制剂后的药代动力学参数 AUC_(0→24)分别为(359.14±55.78)h·ng·ml^(-1)和(351.42±57.84)h·ng·mL^(-1),AUC_(0→∞)分别为(378.74±59.28)h·ng·mL^(-1)和(371.10±59.72)h·ng·mL^(-1),C_(max)分别为(46.80±6.29)ng·mL^(-1)和(48.63±8.47)ng·mL^(-1),T_(max)分别为(1.90±0.50)h和(1.80±0.41)h。相对生物利用度为103.20%±15.08%。结论:该方法简单,准确度高,灵敏度好,可用于非那雄胺在人体内过程研究。方差分析结果表明2种制剂的主要药动学参数之间无明显差异,双单侧 t 检验结果表明两种制剂为生物等效制剂。

药物制剂安全性评价及常见问题分析

非口服途径给药制剂开展制剂安全性试验对评估药物的临床用药风险具有重要的意义。尽管国内外相关指导原则对如何开展制剂安全性试验进行了详细的介绍,但在审评中发现仍有部分产品的申报资料存在缺陷,影响了药物的研发效率。本文对近年来国内外药物制剂安全性相关指导原则信息进行了梳理,并结合具体审评案例对常见的问题进行阐述,以期为相关工作提供参考。

司丙红霉素胶囊的药物动力学

目的:研究司丙红霉素胶囊的药物动力学,为该药进行临床研究提供依据。方法:采用随机、开放试验设计, 30名健康受试者(男女各半),随机分为3组,每组男女各5人。各组分别单剂量口服试验制剂250, 500和750mg。采用HPLC MS法测定给药后不同时间丙酸红霉素和红霉素碱的血药浓度。结果: 30例健康志愿者,全部完成试验,未发生药物不良反应。用3P87软件进行模型分析和参数计算,高、中、低3个剂量组均符合单室模型。口服司丙红霉素胶囊后,丙酸红霉素药物动力学参数为:低剂量组Ka为( 2. 007±1. 281 ) /h,tmax(实测值)为(1. 9±0. 6)h,Cmax为(437. 0±295. 0)μg/L,AUC0-14为(1840. 2±1476. 87 )μg·h/L,Ke为( 0. 329±0. 119 ) /h,T1 /2为(2. 45±0. 9)h;中剂量组Ka为(1. 451±0. 380) /h,tmax(实测值)为(1. 7±0. 3)h,Cmax为(923. 1±217. 5 )μg/L,AUC0-14为(4542. 4±1579. 4 )μg·h/L,Ke为( 0. 237±0. 057 ) /h,T1 /2为( 3. 1±1. 1 )h;高剂量组Ka为(2. 076±1. 559) /h,tmax(实测值)为(1. 7±0. 3)h,Cmax为(1336. 5±366. 0)μg/L,AUC0-14为(7481. 5±2496. 2 )μg·h/L,Ke为(0. 266±0. 051) /h,T1 /2为(2. 7±0. 5 )h。红霉素碱的药物动力学参数为:低剂量Ka为( 1. 410±0. 626) /h,tmax(实测值)为(1. 8?

格列齐特缓释片人体生物等效性研究

目的 观察健康志愿者单剂量和多剂量口服安徽医药科技生产的格列齐特缓释片的血药浓度经时过程，估计相应药代动力学参数，以法国施维雅制药公司生产的缓释片为参比制剂，进行等效性检验。方法 本试验在建立血清中格列齐特的高效液相紫外检测方法的基础上，单剂量和多剂量试验分别选择20名健康男性志愿者，采用随机交文设计方法分别单次或多次口服试验制剂（安徽医药科技产格列齐特缓释片）与参比制剂（法国产格列齐特片缓释片）（30mg），不同时间检测格列齐特的血药浓度，清洗期后交叉给药。

Screening of Chinese Herbal Medicines Resistant to Chicken Escherichia coli and Infectious Laryngotracheitis Virus

[Objective] This study aimed to screen Chinese herbal medicines resistant to Chicken Escherichia coli and infectious laryngotracheitis virus. [Methed] Conven- tional punch method, test tube method and plate dilution method were adopted for in vitro susceptibility test of chicken E, coil strains O5 and O8 using 13 kinds of Chi- nese herbal medicines including Sanguisorba officinalis, Coptis chinensis, Anemar- rhena asphodeloides, Strobilanthes cusia, Agastache rugosa, etc.; chicken embryo inoculation experiment was adopted to screen Chinese herbal medicines resistant to chicken infectious laryngotracheitis virus. [Result] Sanguisorba officinalis, Fructus mume, Rheum officinale, Coptis chinensis, Herba Taraxaci, Anemarrhena asphode- Ioides, Scutellaria baicalensis and Rhizoma Fagopyri Cymosi had ideal antibacterial effect against chicken E. coil strain O5; Sanguisorba officinalis, Fructus mume, Rheum officinale, Coptis chinensis, Herba taraxaci and Rhizoma Fagopyri Cymosi had ideal antibacterial effect against chicken E. coil strain 08; other Chinese herbal medicines showed relatively poor or no antibacterial effect. Results of chicken embryo inoculation experiment showed that nine kinds of Chinese herbal medicines showed relatively strong anti-lLTV effect, including Forsythia suspensa, Radix Isatidis, Fofium isatidis, Flos Ionicerae, Radix codonopsis, Radix astragali, Atractylodes, Radix gly- cyrrhizae, and Pericarpium granati. [Conclusion] The study laid the foundation for fur- ther development of Chinese herbal compound preparations to treat chicken cofibacil- Iosis, infectious laryngotracheitis and other bacterial, viral diseases.

Gastroesophageal reflux disease management according to contemporary international guidelines:A translational study

AIM:To test the Genval recommendations and the usefulness of a short trial of proton pump inhibitor(PPI) in the initial management and maintenance treatment of gastroesophageal reflux disease(GERD)patients. METHODS:Five hundred and seventy seven patients with heartburn were recruited.After completing a psychometric tool to assess quality of life(PGWBI)and a previously validated GERD symptom questionnaire (QUID),patients were grouped into those with esophagitis(EE,n=306)or without mucosal damage (NERD,n=271)according to endoscopy results. The study started with a 2-wk period of high dose omeprazole(omeprazole test);patients responding to this PPI test entered an acute phase(3 mo)of treatment with any PPI at the standard dose.Finally,those patients with a favorable response to the standard PPI dose were maintained on a half PPI dose for a further 3-mo period. RESULTS:The test was positive in 519(89.9%)patients,with a greater response in EE patients(96.4%) compared with NERD patients(82.6%)(P=0.011). Both the percentage of completely asymptomatic patients,at 3 and 6 mo,and the reduction in heartburn intensity were significantly higher in the EE compared with NERD patients(P<0.01).Finally,the mean PGWBI score was significantly decreased before and increased after therapy in both subgroups when compared with the mean value in a reference Italian population. CONCLUSION:Our study confirms the validity of the Genval guidelines in the management of GERD patients. In addition,we observed that the overall response to PPI therapy is lower in NERD compared to EE patients.

A systematic review of treating Helicobacter pylori infection with Traditional Chinese Medicine

AIM: To evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) in the treatment of Helicobacter pylori (H pylori) infection. METHODS: We electronically and manually searched electronic databases, references lists and conferences compilations, and included all randomized clinical trials comparing the treatment of H pylori using TCM with proton pump inhibitor or colloidal bismuth subcitratebased triple therapy as controls. The Jadad score was used to assess trial quality, H pylori eradication rate and the incidence of side effects were taken as outcome measurements, and heterogeneity analysis, meta-analysis and funnel plot analysis were conducted. RESULTS: Sixteen trials were included. The Jadad scores of all the trials were not more than 2. Clinical heterogeneity and substantial statistical heterogeneity existed among the trials (P = 0.001, I 2 = 59%) and meta-analysis was not conducted. The average eradication rates following TCM and triple therapy were 72% and 78% and the incidence of side effects were 2% and 29%, respectively. The funnel plot was obviously asymmetric. CONCLUSION: Available evidence is not convincing enough to show that TCM has the same efficacy as triple therapy in H pylori treatment. TCM may be safer than triple therapy. TCM should not be recommended as monotherapy in H pylori infection.

Decreased Soil Nitrification Rate with Addition of Biochar to Acid Soils

This study was conducted to investigate the effects of mixed biochar on the nitrification rate in acidic soils. A15 N tracer experiment with(15 NH4)2 SO4 was conducted to determine the nitrification rates of 4 acidic agricultural soils with p H 4.03-6.02 in Yunnan Province, Southern China. The accumulation of15 N-NO3-and nitrification rates decreased with the addition of biochar at the end of incubation, suggesting that biochar could be a nitrification inhibitor in acidic fertilized soil. Nitrification rates in soil with p H 4.03 were evidently lower than those in soil with p H 4.81-6.02 with or without biochar. Decreased nitrification rates were detected in the acidic soils with biochar. Soil p H controlled nitrification more than biochar in certain strongly acidic soils.

Natural history of Barrett's esophagus

The natural history of Barrett's esophagus (BE) is difficult to quantify because,by definition,it should describe the course of the condition if left untreated.Pragmatically,we assume that patients with BE will receive symptomatic treatment with acid suppression,usually a proton pump inhibitor,to treat their heartburn.This paper describes the development of complications of stricture,ulcer,dysplasia and adenocarcinoma from this standpoint.Controversies over the definition of BE and its implications in clinical practice are presented.The presence of intestinal metaplasia and its relevance to cancer risk is discussed,and the need to measure the extent of the Barrett's epithelium (long and short segments) using the Prague guidelines is emphasized.Guidelines and international consensus over the diagnosis and management of BE are being regularly updated.The need for expert consensus is important due to the lack of randomized trials in this area.After searching the literature,we have tried to collate the important studies regarding progression of Barrett's to dysplasia and adenocarcinoma.No therapeutic studies yet reported show a clear reduction in the development of cancer in BE.The effect of pharmacological and surgical intervention on the natural history of Barrett's is a subject of ongoing research,including the Barrett's Oesophagus Surveillance Study and the aspirin and esomeprazole cancer chemoprevention trial with interesting results.The geographical variation and the wide range of outcomes highlight the difficulty of providing an individualized risk profile to patients with BE.Future studies on the interaction of genome wide abnormalities in Barrett's and their interaction with environmental factors may allow individualization of the risk of cancer developing in BE.

Development of Novel Therapeutics for Chronic Hepatitis B

Chronic infection of hepatitis B virus (HBV) presents one of the serious public health challenges worldwide. Current treatment of chronic hepatitis B (CHB) is limited, and is composed of interferon and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI). Interferon is poorly tolerated and is only responsive in a small fraction of CHB patients and NRTIs often face the problem of emergence of drug resistance during long-term treatment. The current treatment of CHB can be improved in several ways including genotyping mutations associated with drug resistance before treatment to guide the choice of NRTIs and suitable combinations among NRTIs and interferon. It is important to continue research in the identification of novel therapeutic targets in the life cycle of HBV or in the host immune system to stimulate the development of new antiviral agents and immunotherapies. Several antiviral agents targeting HBV entry, cccDNA, capsid formation, viral morphogenesis and virion secretion, as well as two therapeutic vaccines are currently being evaluated in preclinical studies or in clinical trials to assess their anti-HBV efficacy.

Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction

We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)- AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the 13C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to followup. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%,respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.

The antiemetic effects of magnetotherapy plus granisetron hydrochloride versus granisetron hydrochloride in patients with chemotherapy

Objective:The aim of this study was to observe and compare the antiemetic effectiveness and adverse events of magnetotherapy plus 5-hydroxytryptamine (5-HT3) receptor inhibitor granisetron hydrochloride vs granisetron hydrochloride alone in patients with chemotherapy.Methods:Sixty-four patients were randomized to receive either granisetron hydrochloride alone (control group:granisetron hydrochloride 3 mg intervenous infusion before chemotherapy, from the 1st day of chemotherapy course until the day after chemotherapy course completed) or magnetotherapy plus granisetron hydrochloride (treatment group:the same granisetron hydrochloride regimen plus rotatory magnetotherapy of 1 every day after chemotherapy for 5 begin with chemotherapy).Baseline characteristics were similar in both groups.The patients' emesia was evaluated according to WHO's criteria.The density of 5-HT3 was detected by enzyme-linked immunosorbent assay (ELISA).Results:In the treatment of acute vomiting, there was no significant difference between two groups (P>0.05), but in the treatment of tardive vomiting, the effectiveness in treatment group was better than that in control group (P<0.05).The density of 5-HT3 in treatment group and control group were (225.32±57.29) ng/mL vs (213.00 ±53.29) ng/mL before chemotherapy and (273.88 ±75.42) ng/mL vs (313.17±76.36) ng/mL after chemotherapy (P<0.01); the rate of adverse events was 36.36% and 48.39% respectively in treatment group and control group (P>0.05).Conclusion:Magnetotherapy plus granisetron hydrochloride provide better effectiveness than granisetron hydrochloride alone, and both therapies have synergistic effect.The adverse events didn't raised in treatment group.

Test Bench for the Mechanical Distribution of Predators to Control Insect Pests

In agriculture, chemical insecticides are widely used to protect crops from insect pests. Over a period of years, some insects such as Colorado potato beetle （CPB） succeed in developing resistance to most of the registered chemical insecticides. Consequently, heavy applications of chemical insecticides to control this pest become ineffective on a long-term basis and can lead to serious health and environmental problems. The use of natural enemies to control CPB is an interesting alternative to chemical means However, hand release of predators is not feasible on a large scale in the field. The main objective of this research study was to design and build a test bench to investigate the technical feasibility of mechanically releasing predators. The test bench consisted of a vertical chain conveyor mounted on two vertical shafts driven by an electric motor. Since the predators are small and fragile, they were placed in a specially designed container to preserve their physical integrity. Trials using this test bench showed that a carrier material was required, because most of the predators remained inside the container. The success of this mass predator release system will be highly valuable for the biological control of insect pests in many crops.

Impact of minimally invasive surgery on the treatment of benign esophageal disorders

Thanks to the development of minimally invasive surgery, the last 20 years have witnessed a change in the treatment algorithm of benign esophageal disorders. Today a laparoscopic operation is the treatment of choice for esophageal achalasia and for most patients with gastroesophageal reflux disease. Because the pathogenesis of achalasia is unknown, treatment is palliative and aims to improve esophageal emptying by decreasing the functional obstruction at the level of the gastro-esophageal junction. The refinement of minimally invasive techniques accompanied by large, multiple randomized control trials with long-term outcome has allowed the laparoscopic Heller myotomy and partial fundoplication to become the treatment of choice for achalasia compared to endoscopic procedures, including endoscopic botulinum toxin injection and pneumatic dilatation. Patients with suspected gastroesophageal reflux need to undergo a thorough preoperative workup. After establishing diagnosis, treatment for gastroesophageal reflux should be individualized to patient characteristics and a decision about an operation made jointly between surgeon and patient. The indications for surgery have changed in the last twenty years. In the past, surgery was often considered for patients who did not respond well to acid reducing medications. Today, the best candidate for surgery is the patient who has excellent control of symptoms with proton pump inhibitors. The minimally invasive approach to antireflux surgery has allowed surgeons to control reflux in a safe manner, with excellent long term outcomes. Like achalasia and gastroesophageal reflux, the treatment of patients with paraesophageal hernias has also seen a major evolution. The laparoscopic approach has been shown to be safe, and durable, with good relief of symptoms over the long-term. The most significant controversy with laparoscopic paraesophageal hernia repair is the optimal crural repair. This manuscript reviews the evolution of these techniques.

Progress in clinical trial of histone deacetylase(HDAC) inhibitors for non-small cell lung cancers

Histone deacetylase(HDAC) inhibitors, which represent a structurally diverse group of molecules, have emerged as a novel therapeutic class of molecules with significant anticancer potential. Vorinostat and romidepsin, known as the first generation of HDAC inhibitors, were approved in the United States for the treatment of T-cell lymphomas. Preliminary activity of HDAC inhibitors has also been observed in non-small cell lung cancer(NSCLC) in combination with the existing treatment regimens, of which is the focus of the current review.

奥美拉唑碳酸氢钠干混悬剂和肠溶制剂在健康人体的药动学对比研究

目的:研究奥美拉唑碳酸氢钠干混悬剂(试验制剂)和肠溶制剂(参比制剂)在健康人体内的药动学差异。方法:采用单中心、开放、随机、自身交叉对照试验,12例志愿受试者(男女各半)于不同试验周期分别餐后单次、空腹单次和多次口服20 mg试验制剂和参比制剂。用HPLC-MS/MS法测定血浆中奥美拉唑浓度,用Phoenix^(TM) Win Nonlin 6.1药动学软件计算主要药动学参数。结果:试验制剂空腹单、多次给药的AUC与参比制剂一致,Tmax较参比制剂快,空腹单次给药试验制剂C_(max)较参比制剂高,多次给药差异不明显;t1/2和参比制剂比较无统计学差异,高脂高热餐后给药,试验制剂的AUC小于参比制剂。结论:试验制剂与参比制剂相比:达峰时间较快,空腹单次和多次给药AUC无明显差异,饮食会抑制试验制剂的吸收;多次给药2种制剂的AUC均明显增大;建议奥美拉唑碳酸氢钠干混悬剂空腹服用。

Responses of Ammonia-Oxidizing Bacteria and Archaea in Two Agricultural Soils to Nitrification Inhibitors DCD and DMPP: A Pot Experiment

Taking two important agricultural soils with different pH, brown soil （Hap-Udic Luvisol） and cinnamon soil （Hap-Ustic Luvisol）, from Northeast China, a pot culture experiment with spring maize （Zea mays L.） was conducted to study the dynamic changes in the abundance and diversity of soil ammonia-oxidizing bacteria （AOB） and ammonia-oxidizing archaea （AOA） populations during maize growth period in response to the additions of nitrification inhibitors dicyandiamide （DCD） and 3,4-dimethylpyrazole phosphate （DMPP） by the methods of real-time polymerase chain reaction （PCR） assay, PCR-denaturing gradient gel electrophoresis （DGGE）, and construction of clone library targeting the amoA gene. Four treatments were established, i.e., no urea （control）, urea, urea plus DCD, and urea plus DMPP. Both DCD and DMPP inhibited growth of AOB significantly, compared to applying urea alone. Soil bacterial amoA gene copies had a significant positive linear correlation with soil nitrate content, but soil archaeal amoA gene copies did not. In both soils, all AOB sequences fell within Nitrosospira or Nitrosospira-like groups, and all AOA sequences belonged to group 1.1b crenaxchaea. With the application of DCD or DMPP, community composition of AOB and AOA in the two soils had less change except that the AOB community composition in Hap-Udic Luvisol changed at the last two growth stages of maize under the application of DCD. AOB rather than AOA likely dominated soil ammonia oxidation in these two agricultural soils.