2,3-吲哚醌在大鼠体内的药代动力学研究

目的考察单次静脉注射和口服给予大鼠2,3-吲哚醌后的药代动力学,为该药的新药开发提供依据。方法大鼠给药后经眼眶静脉采大约0.25 ml血液,采集时间点为：给予受试物前（0hr）和给予受试物后5 min,15min,30 min,1 h,2 h,4 h,6 h,8 h和24 h。血液样本采集后置于冰上,并立即取出50μl全血采用甲醇蛋白沉淀进行预处理,奎硫平作为内标。预处理后样品采用LC/MS/MS法进行测定,并用药动学处理软件WinNonlin 5.2采用非房室模型计算相关药代动力学参数。结果 Sprague Dawley大鼠静脉注射和口服两种制剂的药动学参数（平均值±标准偏差）如下。静脉注射：Tmax为0.83±0.29 hr,Cmax为141.53±10.99μg/L,T1/2为1.68±0.84 hr,AUC0-t为1068.15±389.06μg.hr/L,AUC0-∞为1211.19±469.18μg.hr/L,Vz为4.13±1.41 L/kg,CLz为1.89±0.94 L/hr/kg;口服：Tmax为0.05±0.00 hr,Cmax为1725.53±469.70 ng/ml,t 1/2为4.21±2.78 hr,AUC0-t为7711.21±2533.12μg.hr/L,AUC0-∞为7986.07±2623.38μg.hr/L,以AUC0-t计算,生物利用度平均为57.75±18.97%。结论 2,3-吲哚醌大鼠体内消除较快,可能存在非线性消除,口服吸收较好。     

SIRT1 is significantly elevated in mouse and human prostate cancer

Evidence suggests that the histone deacetylase, SIRT1, is a mediator of life span extension by calorie restriction; however, SIRT1 may paradoxically increase the risk of cancer. To better understand the relationship among SIRT1, energy balance, and cancer, two experiments were done. First, a transgenic mouse model of prostate cancer (transgenic adenocarcinoma of mouse prostate; TRAMP) was used to determine the role of energy balance on SIRT1 expression and the effect of cancer stage on SIRT1 and hypermethylated in cancer-1 (HIC-1). Second, immunohistochemistry was done on human prostate tumors to determine if SIRT1 was differentially expressed in tumor cells versus uninvolved cells. Results show that SIRT1 is not increased in the dorsolateral prostate (DLP) of calorie-restricted mice during carcinogenesis. In contrast, when examined in the DLP as a function of pathologic score, SIRT1 was significantly elevated in mice with poorly differentiated adenocarcinomas compared with those with less-advanced disease. HIC-1, which has been shown to regulate SIRT1 levels, was markedly reduced in the same tumors, suggesting that a reduction in HIC-1 may be in part responsible for the increased expression of SIRT1 in prostatic adenocarcinomas. Furthermore, immunostaining of human prostate tumors showed that cancer cells had greater SIRT1 expression than uninvolved cells. In conclusion, DLP SIRT1 expression from calorie-restricted mice was not altered during carcinogenesis. However, SIRT1 expression was increased in mice with poorly differentiated adenocarcinomas and in human prostate cancer cells. Because SIRT1 may function as a tumor promoter, these results suggest that SIRT1 should be considered as a potential therapeutic target for prostate cancer.     

老年性痴呆与血管性痴呆患者睡眠障碍的对照研究

目的:研究老年性痴呆(AD)和血管性痴呆(VD)患者睡眠障碍的特点及相关性。方法:对31例AD患者和30例VD患者采用阿森斯(Athens)失眠量表调查评分及临床资料比较分析。对研究对象进行筛选分组。从8个方面详细记录睡眠情况,按量表现规定进行评定。结果:AD患者和VD患者总体睡眠状况比较有显著性差异(t=2.251,P<0.05)。睡眠状况各因子比较,在总睡眠质量、白天情绪、白天思睡等3个方面无显著性差异(P>0.05)。在早醒、白天身体功能方面,两者有极显著差异(P<0.01)。在入睡时间、夜间苏醒、总睡眠时间等两者存在显著性差异(P<0.05)。结论:AD患者和VD患者都有睡眠障碍,AD患者在早醒、白天身体功能、夜间苏醒、总睡眠时间等方面都比VD患者差,而VD患者在入睡时间上比AD患者明显延迟。     

Evaluation of the detection of PML-RARα fusion gene in acute promyelocytic leukemia to monitor minimal residual disease

Objective To investigate the kinetics of PML-RARα fusion gene in acute promyelocytic leukemia(APL)to monitor minimal residual disease(MRD). Methods In induction therapy,consolidation and maintenance therapy courses, PML-RARα fusion gene was performed by RT-PCR. Results The long-term follow-up of 18 cases achieved complete remission (CR),two cases experienced molecular relapse. One case relapsed at 4 months after CR1 and achieved CR2 after induction therapy. However, molecular and hematology relapsed again at 2 months after CR2 and re-achieved CR3. The other case relapsed at 74 months after CR1 and achieved CR2 after induction treatment, who had survived for 106 months until the end of follow-up. Conclusion RT-PCR assay for detection of PML-RARα should be performed regularly during CR period so as to find molecular relapse eady. Hematological relapse could potentially be averted through treatment modification according to molecular monitoring results of PML-RARα.     

非穿透性小梁切除术联合人羊膜植入临床观察

目的：观察非穿透性小梁切除术联合人羊膜植入的临床效果。方法：对18例（30眼）中、晚期开角型青光眼进行非穿透性小梁切除术联合人羊膜植入，术后观察视力、视野、眼压及滤过泡形成情况。结果：术后随访3－9月，视力、视野稳定，眼压≤20mmHg(1mmHg=0.133kPa)，滤过泡形成良好，并发症少。结论：非穿透性小梁切除术 联合人羊膜植入治疗开角型青光眼，能有效降低眼压，形成功能性滤过泡和并发症少等优点，是治疗开角型青光眼较理想的方法。     

The trouble with family medicine

BACKGROUND: The trouble with family medicine is that the perceptual framework it uses to view the phenomena of health and illness is at variance with the frameworks traditionally used by medicine generally. This creates difficulties in communication between those in family medicine and those in other disciplines, and sometimes leads to misunderstanding of the nature of the discipline of family medicine and its place in the health care system. Those who practise family medicine need to be 'multilingual', able to understand and speak the language and use the metaphors of family medicine, yet equally able to use the language and metaphors of other disciplines. OBJECTIVES: This paper, which begins with a clinical scenario, reviews the contemporary biomedical paradigm, proposes an alternative, and examines the conceptual frameworks which underpin the discipline of family medicine.      

Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a single intravenous injection of interleukin-8

Interleukin-8 (IL-8) is a chemoattractant cytokine involved in chemotaxis and activation of neutrophils. Because in vivo administration of IL-8 induces mobilization of hematopoietic stem cells in mice, we assessed the mobilizing properties of IL-8 in rhesus monkeys. Recombinant human IL-8 was administered as a single intravenous injection at doses of 10, 30, and 100 micrograms/kg to rhesus monkeys (age, 2 to 3 years; weight, 2.5 to 4.5 kg). Venous blood samples were obtained at time intervals ranging from 1 to 480 minutes after IL-8 administration. Cell counts, colony-forming unit-Mix assays, and fluorescence-activated cell sorter analysis were performed. Plasma was harvested to assess IL-8 levels. A time-controlled bolus intravenous injection of 100 micrograms IL-8 per kilogram of body weight resulted in peak IL-8 plasma levels up to 5 micrograms/mL. The calculated half-time life of free IL-8 was 9.9 +/- 2.2 minutes. IL-8 injection resulted in instant neutropenia that was due to pulmonary sequestration, as shown using 99mTc-labeled leukocytes. Within 30 minutes after IL-8 injection, neutrophilia developed with counts up to 10-fold greater than baseline levels. The numbers of hematopoietic progenitor cells (HPCs) increased from 45 +/- 48/mL to 1,382 +/- 599/mL of blood at 30 minutes after injection of 100 micrograms IL-8 per kilogram of bodyweight (mean +/- SD, n = 8). Individual animals showed 10- to 100-fold increase in numbers of circulating HPCs that returned to almost pretreatment values (92 +/- 52 CFU/mL) at 240 minutes after the injection of IL-8. Immunophenotyping showed no significant changes in lymphocyte (sub)populations. A second bolus injection of IL-8 with an interval of 72 hours resulted in similar numbers of mobilized stem cells as observed after the first injection, showing that no tachyphylaxis had occurred. We conclude that IL-8 induces mobilization of HPCs from the bone marrow of rhesus monkeys in a rapid and reproducible fashion. Therefore, IL-8 may be a potentially useful cytokine in the setting of blood stem cell transplantation.     

Recovery of contact hypersensitivity responses following murine bone marrow transplantation: comparison of gamma-irradiation and busulfan as preparative marrow-ablative agents

Bone marrow transplantation (BMT) is often followed by significant morbidity and mortality due to protracted immunodeficiency. We have hypothesized that the bone marrow-ablative regimen may delay the recovery of normal immune function following transplantation by impairing the interaction of host endothelial cells with circulating graft-derived lymphocytes. This report compares the relative effects of busulfan (an alkylating drug) and gamma-irradiation on the tissue- specific localization potential of lymphocytes and the eventual recovery of immune function within syngeneic murine transplant recipients. Localization of normal lymphocytes into peripheral lymph nodes of irradiated BMT recipients was markedly less (less than 50%) than in busulfan-treated or normal mice over the first 2 months post- BMT. This finding correlated with irradiation-induced endothelial cell edema and microvascular occlusions within lymphocyte-receptive areas of the nodal microvasculature. The effect of both preparative regimens on the recovery of contact hypersensitivity (CHS) was also analyzed. This response recovered more quickly (between 1 and 2 months) in busulfan- pretreated animals. Further experiments demonstrated that the decrease in CHS responsiveness appeared, in part, related to a depression in the capacity of lymphocytes to localize into skin sites of antigen deposition within irradiated mice. The impairment of tissue-specific lymphocyte localization may represent a novel mechanism by which whole body irradiation can contribute to delayed immunologic reconstitution following bone marrow transplantation.