Bacterial ghosts (BGs)—Advanced antigen and drug delivery system

Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy.     

Individualized Mycophenolate Mofetil Dosing Based on Drug Exposure Significantly Improves Patient Outcomes After Renal Transplantation

Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.     

利福昔明对比环丙沙星治疗急性肠炎临床研究

目的　研究利福昔明对比环丙沙星治疗急性肠炎的有效性和安全性。　方法　采用随机对照方法 ,共治疗 5 1例急性肠炎。利福昔明治疗 2 5例 ,环丙沙星 2 6例 ,用药时间方法相同。观察治疗前后临床症状、大便性状、大便次数、便常规、血常规、尿常规及肝肾功能 ,以了解其疗效及不良反应情况。　结果　利福昔明组 (治疗组 )与环丙沙星组 (对照组 )相比 ,显效率分别为 92 .0 %和 80 .8% ,总有效率分别为 92 .0 %和 96 .2 % ,止泻时间治疗组 2 8.6 7± 15 .92h ,对照组 36 .12± 2 0 .70h ,均未见明显毒副作用。以上各项指标及两组在治疗过程中大便次数变化、大便常规复常率经统计学处理均无显著性差异 (P >0 0 5 )。　结论　利福昔明可用于治疗急性肠炎 ,与环丙沙星比较 ,疗效相仿 ,但耐受性好 ,口服不吸收 ,故值得推广     

Zolpidem induced nocturnal sleep‐related eating disorder (NSRED) in a male patient

Nocturnal Sleep‐Related Eating Disorder (NSRED) is a well‐documented sleeping disorder where the person is reported to experience bizarre eating behavior during sleep. Although various causes are implicated in this disorder, role of drugs cannot be ruled out. Here we narrate an interesting rare case report of a drug‐induced new onset NSRED, where a 45‐year‐old man on zolipdem performed an unexpected and bizarre eating behavior during somnambulistic state, type of which has not been reported earlier in the literature. The case falls under even rarer category as such behavior in sleep is reported mainly in woman. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2009     

化疗药物对轴型皮瓣血运影响的组织学观察

目的探讨抗癌药物动脉灌注后对局部轴型皮瓣血运影响的组织学评价。方法在猪腹部的腹壁上动脉插管灌注抗癌药物,10d后在猪腹部形成以腹壁上血管为蒂的岛状皮瓣,通过对灌注区域轴型血管供养的岛状皮瓣的成活率、光镜、透射电镜及血管铸型透明标本的组织学观察,显示其血管结构及构筑的变化。结果抗癌药物用于局部动脉灌注后,使局部轴型血管支配的血管网有损伤的表现,岛状皮瓣远端的血运显著降低。结论抗癌药物经动脉灌注后可影响局部轴型皮瓣的血运,使皮瓣血供的安全范围缩小,为提高相关修复手术的成功率提供可靠的科学依据。     

外加磁场对半乳糖化白蛋白磁性阿霉素纳米粒在大鼠体内分布影响的研究

目的观察半乳糖化白蛋白磁性阿霉素纳米粒(ADR-GHMN)在正常肝脏中的靶向性,并观察ADR-GHMN在全身各脏器的分布特征及外加磁场对其分布的影响.方法大鼠正中开腹,肝动脉插管并固定,肝动脉注射125I-ADR-GHMN(相当于阿霉素0.5 mg/kg),左外叶加磁场,磁场应用30 min,移去磁场后,动物立即处死;对照组:肝动脉注射ADR-GHMN,左外叶不加磁场,30min后,移去磁场后,动物立即处死,立即取靶区肝、非靶区肝、肾、心、肺、小肠、脾及周围血作γ计数.肝组织作病理切片.结果注入的纳米粒75～85%分布于肝脏,其它脏器极少.病理切片显示磁区小动脉见大量纳米粒存在,对照组及非磁区肝中纳米粒很少见.结论ADR-GHMN在正常肝组织中有明显的磁靶向性;在磁场作用下,ADR-GHMN主要分布于肝脏,其它脏器含量很少;试验组肾、心、肺、小肠、脾及外周血于对照组的放射活性比较明显降低,表明磁性物质的存在使这些脏器的相对药物暴露明显减少.     

Clinical parameters that predict histology of postchemotherapy retroperitoneal lymph node mass in testicular cancer

BACKGROUND: Since the advent of cisplatin-based chemotherapy, the majority of metastatic testicular cancers can be cured by chemotherapy followed by retroperitoneal lymph node dissection (RPLND). However, postchemotherapy RPLND confers no therapeutic benefit if the residual mass contains no viable cells. Therefore, to determine which parameters predict a patient's likelihood of having only necrosis in the residual mass, we retrospectively analyzed clinical parameters of patients who underwent postchemotherapy RPLND. METHODS: Data from 27 patients with metastatic testicular cancer were analyzed. The histology of the primary tumor was seminoma in 11 cases and non-seminoma in 16 cases. All of the patients with non-seminoma showed a normalization of tumor markers after chemotherapy. Analysis of clinical parameters included data for the initial histology, pretreatment tumor marker levels, postchemotherapy retroperitoneal mass size, and the histology of the dissected RPLNs. RESULTS: Histological examination of dissected RPLNs showed residual tumor in 27% of seminoma patients and 38% of non-seminoma patients. In seminoma patients, no viable cells were found in all six patients with pretreatment lactate dehydrogenase (LDH) levels below 7.5 times the upper limit of normal, or in all five of the patients with postchemotherapy RPLNs less than 2.5 cm. In non-seminoma patients, no viable cells were found in nine of 10 patients with pretreatment alpha-fetoprotein (AFP) levels less than 2700 ng/mL, or in eight of nine patients with residual mass less than 2.5 cm. CONCLUSIONS: Both postchemotherapy RPLN mass size and pretreatment tumor marker levels are possible predictors for necrosis of the residual mass in testicular cancer patients.     

工作作为药物及酒精滥用者有效的干预策略和治疗方法

1Introduction Substanceabusecontinuestobeamongthemostsevereso cialandcostlyhealthproblemsdevastatingindividualsandtheir familiesintheUnitedStates.Initssimplestdefinition,sub stanceabuseisthecontinueduseofalcoholorotherdrugsde spiteknowledgeofhavingapersistentsocial,vocational,psy chologicalorphysicalproblemthatiscausedorexacerbatedby theuseofalcoholorotherdrugs(DSMIV TR,1994).All drugsofabuse,includingalcohol,aretoxicandcannegatively impacteverysysteminthehumanorganism.Protractedsub stance…     

1040例在院病人抗生素一日使用调查报告

目的了解住院病人抗生素使用情况。方法采用横断面调查的方法时我院2005年7月27日所有住院病人抗生素使用情况进行调查。结果抗生素日使用率为34．81％（304／1040），治疗用抗生素占39．67％（144／363），预防用占16．25％（59／363），治疗＋预防占44．08％（160／363），抗生素单用和二联占95．04％（344／363），三联及以上者4．96％（18／363），抗生素日使用种类47种，病原体送检率7．57％（23／304）。结论我院抗生素日使用率不高，抗生素联合使用总体较好，但仍有病原送检率低、抗生素使用品种多、起点高、部分囤术期抗生素预防用药的时机不合理等现象，建议加强宣传教育力度，提高监测速度和指导医师合理用药。